Carbostyril compound

FIELD: chemistry.

SUBSTANCE: invention relates to novel carbostyril compounds of general formula (1) or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds, having activity on promotion of TFF2 production, a pharmaceutical composition based on said compounds, an agent based on disclosed compounds used in case of a disorder where up-regulation of TFF has a prophylactic and/or therapeutic effect, use of disclosed compounds to prepare said agent and a method of producing disclosed compounds. The invention also relates to novel specific carbostyril compounds or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds. In structural formula (1), A is a direct bond, a lower alkylene group or lower alkylidene group, X is an oxygen or sulphur atom, the bond between positions 3 and 4 of the carbostyril backbone is a single bond or a double bond, R4 and R5 each denotes a hydrogen atom provided that, when the bond between positions 3 and 4 of the carbostyril backbone is a double bond, R4 and R5 can instead be bonded to each other in form of a -CH=CH-CH=CH- group, and R1, R2 and R3 assume values given in the claims.

EFFECT: high efficiency of compositions based on said compounds.

32 cl, 23 dwg, 184 tbl, 1535 ex

 

The technical field to which the invention relates.

The invention relates to barbastella connection.

Background of invention

The TFF family factors (trefoil factors) is a group of highly stable peptides with three leaf leveraging structure formed of six cysteine residues. Up to the present time identified three TFF peptide (TFF1, TFF2 and TFF3) in humans. The TFF peptides present in associated with mucus tissue, such as the digestive tract, and are secreted mainly by cells secreting mucus. The increased expression of TFF-peptides occurs near the damaged mucosa and in regenerating glands. It is known that the basic functions of TFF-peptides are increased cellular migration methods (motogenic effects), the protection of cells and suppression of apoptosis [Nature Reviews, Molecular Cell Biology, Vol. 4: 721-732(2003)].

TFF2 is a peptide of 106 amino acid residues, originally isolated from the pancreas of pigs. TFF2-peptide-rich cells of the mucous membrane of the cervix stomach, privratnikovym the stomach, the mucous membrane around the ulcers, regenerative mucosa, overlying a layer of mucus, brunerovy cancer and so on.

Already confirmed by experiments on rats that TFF2 prevents the development of colitis and stomach ulcers, as well as accelerating aisleyne [Gastroenterology 108: 108-116(1995); Gastroenterology 110: 489-497(1996); Alim. Pharmacol. Ther., 14: 1033-1040(2000); Gut, 45: 516-522(1999); Gut, 44: 636-642, 1999; and J. Leukoc. Biol., Vol. 75: 214-223(2004)].

Other experiments showed that mice deprived of TFF2 caused by indomethacin gastric ulcers aggravated [J. Clin. Invest., Vol. 109: 193-204(2002)].

In Eur. J. Clin. Invest., 32: 519-527(2002) described the ability of TFF2 to stabilize the mucus.

In Am. J. Respir. Cell Mol. Biol., Vol. 29: 458-464(2003) indicated that TFF2 may be involved in the regulation of proliferation of damaged epithelial tissues of the respiratory tract.

From the above it can be understood that TFF2 plays a key role in the protection from damage of mucous membranes and its cure. As for diseases, which can probably be cured with the help of TFF2, then improvement can be expected therapeutic effects, contributing to the production of endogenous TFF2.

In Gastroenterology, 126: 796-808(2004) revealed that TFF3 is effective in the treatment of mucositis of the digestive tract, such as stomatitis caused by the introduction of carcinostatic. In Science, Vol. 274: 259-262(1996) and Gastroenterology, 119: 691-698(2000) from the fact that mice deprived of TFF1, developed cancer of the stomach, it is concluded that TFF1 gene can act as a suppressor gene tumor. In Nature Reviews, Molecular Cell Biology, Vol. 4: 721-732(2003) and Int. J. Mol. Med., 12: 3-9(2003) assumes that TFF2 may act in the same way as are TFF1 and TFF3.

As compounds for increasing the regulation of the expression of TFF2 known [FEBS Lett, 488: 206-210(2001); Alim. Pharmacol. Ther., 18 (suppl. 1): 119-125(2003); FEBS Lett., 558: 33-38(2004) and Can. Res., 61: 2424-2428(2001)] ligands for receptor-γ activated peroxisome proliferation (PPAR γ) (e.g., indomethacin, aspirin, prostaglandin J2and troglitazone).

Among the various proteins keratinocyte growth factor (KGF), reportedly enhances the expression of TFF2 and TFF3 in the lower gastrointestinal tracts of rats [Am. J. Physiol. Regul. Integr. Comp. Physiol., 284: R564-R573(2003)].

Some studies suggest the pharmacological action of TFF-peptides as such and suggest the possibility of their application in clinical medicine (WO92/14837, WO02/102403 and WO02/46226).

In WO01/002377 and WO02/051419 describes the various connections with the Deputy containing 2,4-dioxothiazolidine or 4-oxo-2-thioxothiazolidine part heteroaryl skeleton, such as quinoline. In these documents disclosed that these compounds exhibit inhibitory activity towards the telomeres.

Description of the invention

The aim of the present invention is to provide new compounds capable of increasing the regulation of TFF, and the creation of a pharmaceutical composition for prevention and/or treatment of diseases of the digestive tract, diseases of the oral cavity, upper respiratory tract diseases, respiratory diseases, eye diseases, malignant tumors and/or RA is by increasing regulation of TFF.

The authors of the present invention conducted extensive research to create a new connection, is able to improve the regulation of endogenous TFF, and as a result discovered that carbocyanine compounds of the following formula (1) may exercise the increasing regulation of endogenous TFF, in particular TFF2. Based on these results, it was established the present invention.

In accordance with the present invention offers carbocyanine connection, the tool containing the specified connection, use the specified connection, a method of treating disorders and the way to obtain this connection, as described below in paragraphs 1-35.

Paragraph 1. Carbocyanine the connection represented by the General formula (1)

or its salt

where a represents a direct bond, lower alkylenes group or lower alkylidene group;

X represents an oxygen atom or a sulfur atom;

the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond;

R4and R5each represents a hydrogen atom, provided that when the bond between positions 3 and 4 barbastelle skeleton is a double bond, R4and R5instead, can be associated with each other in the form of a group-CH=CH-CH=CH-;

R1represents the FDS is th one of the following substituents (1-1)-(1-29):

(1-1) a hydrogen atom,

(1-2) a lower alkyl group,

(1-3) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of phenyl group, lower alkyl groups, lower alkoxygroup, halogen atoms, groups(B)1NR6R7, nitro, carboxypropyl, lower alkoxycarbonyl groups, cyanopropyl, phenyl(lower)alkoxygroup, fenoxaprop, piperidinyl(lower)alkoxycarbonyl groups, amino(lower)alkoxycarbonyl groups, optionally substituted by one or more cycloalkyl groups, 2-imidazoledicarboxylic groups, optionally substituted in the 2-imidazoline ring by one or more lower alkylthiophene, 3-pyrrolidinylcarbonyl groups, optionally substituted 3-pyrrolinone ring by one or more lower alkyl groups, thiazolidinediones groups, optionally substituted in thiazolidinone ring of the phenyl group, 3-azabicyclo[3.2.2]noninterpolating groups, piperidinyl(lower)alkyl groups, aniline(lower)alkyl group, optionally substituted in the amino group by one or more lower alkyl groups, phenylthio(lower)alkyl groups, indolyl(lower)alkyl groups and piperidinylcarbonyl groups, optionally substituted in Pipa is adinova ring by one or more lower alkyl groups,

(1-4) cycloalkyl(lower)alkyl group,

(1-5) phenoxy(lower)alkyl group,

(1-6) naphthyl(lower)alkyl group,

(1-7) a lower alkoxy(lower)alkyl group,

(1-8) carboxy(lower)alkyl group,

(1-9) low alkoxycarbonyl(lower)alkyl group,

(1-10) pyridyl(lower)alkyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms; piperidinyl groups; morpholinopropan; piperazinilnom groups, optionally substituted in piperazinovom ring by one or more members selected from the group consisting of a phenyl group and lower alkyl group; thienyl group; phenyl group; peredelnyh groups; piperidinyl(lower)alkyl groups; phenylthio(lower)alkyl groups; biphenylene groups; (lower)alkyl groups, optionally substituted by one or more halogen atoms; pyridylamino; pyridylcarbonyl; lower alkoxygroup; aniline(lower)alkyl group, optionally substituted in the amino group by one or more lower alkyl groups; and inlinegroup, optionally substituted in the amino group by one or more lower alkyl groups,

(1-11) cyano(lower)alkyl group,

(1-12) group-A1-CONR8R9,

(1-13) the group following the th formula

(1-14) phenyl group,

(1-15) hinely(lower)alkyl group,

(1-16) lower alkoxy(lower)alkoxy-substituted lower alkyl group,

(1-17) replacement lower alkyl group,

(1-18) thiazolyl(lower)alkyl group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of halogen atoms, phenyl group, thienyl groups and peredelnyh groups,

(1-19) a lower alkyl group, optionally substituted by one or more halogen atoms,

(1-20) lower alkylsilane(lower)alkyl group,

(1-21) phenoxy(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; halogen atoms; lower alkenyl groups; cycloalkyl groups; nitro and phenyl groups,

(1-22) phenylthio(lower)alkyl group, optionally substituted in the phenyl ring by one or more halogen atoms,

(1-23) piperidinyl(lower)alkyl group, optionally substituted in piperidinium ring by one or more members selected from the group consisting of phenyl(lower)alkyl groups and phenyl groups which,

(1-24) piperazinil(lower)alkyl group, optionally substituted in piperazinovom ring by one or more phenyl groups,

(1-25) 1,2,3,4-tetrahydroisoquinoline(lower)alkyl group,

(1-26) naphthyloxy(lower)alkyl group,

(1-27) benzothiazolinone(lower)alkyl group, optionally substituted in benzothiazoline ring by one or more alkyl groups,

(1-28) a lower alkyl group substituted by one or more members selected from the group consisting of chinalanoxin and ethanolammonium,

(1-29) pyridyloxy(lower)alkyl group, optionally substituted in the pyridine ring with one or more lower alkyl groups;

R2represents one of the following substituents (2-1)to(2-33):

(2-1) a hydrogen atom,

(2-2) the lower alkoxygroup,

(2-3) a lower alkyl group,

(2-4) carboxy(lower)alkoxygroup,

(2-5) the lowest alkoxycarbonyl(lower)alkoxygroup,

(2-6) a hydroxy-group,

(2-7) phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkylthio, optionally substituted by one or more halogen atoms; the bottom is their alkoxygroup; nitro; lower alkylsulfonyl groups; lower alkoxycarbonyl groups; phenyl(lower)alkenyl groups; lower alkanoyloxy and 1,2,3-thiadiazolyl groups,

(2-8) piperidinyl(lower)alkoxygroup, optionally substituted in piperidinium ring by one or more lower alkyl groups,

(2-9) aminosilane lower alkoxygroup, optionally substituted by one or more lower alkyl groups,

(2-10) the lower alkenylacyl,

(2-11) pyridyl(lower)alkoxygroup, optionally substituted in the pyridine ring with one or more lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms,

(2-12) the lower alkynylamino,

(2-13) phenyl(lower)alkyloxy,

(2-14) phenyl(lower)alkenylacyl,

(2-15) furyl(lower)alkoxygroup, optionally substituted in the furan ring by one or more lower alkoxycarbonyl groups,

(2-16) tetrazolyl(lower)alkoxygroup, optionally substituted in tetrazolium ring one member selected from the group consisting of phenyl groups, a phenyl(lower)alkyl groups and cycloalkyl(lower)alkyl groups,

(2-17) 1,2,4-oxadiazolyl(lower)alkoxygroup, optionally substituted in 1,2,4-oxadiazolines the phenyl ring is Noah band moreover, the phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups,

(2-18) isoxazolyl(lower)alkoxygroup, optionally substituted in isoxazoline ring by one or more lower alkyl groups,

(2-19) 1,3,4-oxadiazolyl(lower)alkoxygroup, optionally substituted in 1,3,4-oxadiazole ring of the phenyl group, and a phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups,

(2-20) lower alkanoyl(lower)alkoxygroup,

(2-21) thiazolyl(lower)alkoxygroup, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more halogen atoms,

(2-22) piperidinyloxy, optionally substituted in piperidinium the ring one or more benzoline groups, each bentely Deputy optionally substituted in the phenyl ring by one or more halogen atoms,

(2-23) thienyl(lower)alkoxygroup,

(2-24) phenylthio(lower)alkoxygroup,

(2-25) carbamoylmethyl lower alkoxygroup, optionally substituted by one or more dissimilarity groups,

(2-26) benzoyl(lower)alkoxygroup,

(2-27) pyridylcarbonyl(lower)alkoxygroup,

(2-28) imidazolyl(lower)alkoxygroup, optionally substituted in the imidazole ring by one or more phenyl(lower)alkyl groups,

(2-29) phenoxy(lower)alkoxygroup,

(2-30) phenyl(lower)alkoxy-substituted lower alkoxygroup,

(2-31) 2,3-dihydro-1H-ingenjorsfirma,

(2-32) isoindoline(lower)alkoxygroup, optionally substituted in isoindoline the ring one or more exography,

(2-33) phenyl group;

R3represents one of the following substituents (3-1)to(3-19):

(3-1) a hydrogen atom,

(3-2) a lower alkyl group,

(3-3) replacement lower alkyl group,

(3-4) cycloalkyl(lower)alkyl group,

(3-5) carboxy(lower)alkyl group,

(3-6) the lowest alkoxycarbonyl(lower)alkyl group,

(3-7) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; phenyl groups; lower alkoxycarbonyl groups; fenoxaprop; lower alkylthio; lower alcalali nalnyh groups; phenyl(lower)alkoxygroup and amino groups, optionally substituted by one or more lower alkanolamine groups,

(3-8) naphthyl(lower)alkyl group,

(3-9) furyl(lower)alkyl group, optionally substituted in the furan ring by one or more lower alkoxycarbonyl groups,

(3-10) thiazolyl(lower)alkyl group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more optionally halogen-substituted lower alkyl groups,

(3-11) tetrazolyl(lower)alkyl group, optionally substituted in tetrazolium ring by one or more lower alkyl groups,

(3-12) benzothieno(lower)alkyl group, optionally substituted in benzothiophenes the ring one or more atoms of halogen,

(3-13) the lower alkylamino group,

(3-14) lower alkenylphenol group,

(3-15) phenyl(lower)alkenylphenol group,

(3-16) benzoimidazolyl(lower)alkyl group,

(3-17) pyridyl(lower)alkyl group,

(3-18) imidazolyl(lower)alkyl group, optionally substituted in the imidazole ring by one or more phenyl(lower)alkyl groups is,

(3-19) hinely(lower)alkyl group;

B represents a carbonyl group or a group-NHCO-;

l is 0 or 1;

R6and R7each independently represents one of the following substituents (4-1)-(4-79):

(4-1) a hydrogen atom,

(4-2) a lower alkyl group,

(4-3) the lower alkanoyloxy group,

(4-4) the lower alkylsulfonyl group, optionally substituted by one or more halogen atoms,

(4-5) alkoxycarbonyl group, optionally substituted by one or more halogen atoms,

(4-6) replacement lower alkyl group,

(4-7) pyridylcarbonyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of pyrrolidine groups and halogen atoms,

(4-8) pyridyloxy group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of lower alkyl groups and lower alkoxygroup,

(4-9) pyridyl(lower)alkyl group,

(4-10) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; fenoxaprop; lower alkoxygroup, optionally substituted one linescale halogen atoms; lower alkylthio; lower alkylsulfonyl groups; amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups; pyrrolidinyl groups, optionally substituted in the pyrolidine ring one or more exography; piperidinyl groups, optionally substituted in piperidinium ring by one or more lower alkyl groups; lower alkenyl groups; aminosulfonyl group; a hydroxy-group; carbamoyl groups, optionally substituted by one or more lower alkyl groups; phenyl(lower)alkoxygroup and ceanography,

(4-11) cycloalkyl group, optionally substituted in cycloalkene ring by one or more lower alkyl groups,

(4-12) benzoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; fenoxaprop; phenyl group; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; lower alkanoyl groups; nitro; ceanography; amino groups, optionally substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups; pyrrolidin the selected groups, optionally substituted in the pyrolidine ring one or more exography; pyrrolidine groups; pyrazolidine group; 1,2,4-triazolyl groups and imidazolinium groups,

(4-13) benzoyloxy group substituted in the phenyl ring by one or more lower alkylenedioxy,

(4-14) cycloalkylcarbonyl group,

(4-15) fuelleborni group,

(4-16) afterburning group,

(4-17) phenoxycarbonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, lower alkyl groups, halogen atoms and nitro,

(4-18) phenyl(lower)alkoxycarbonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and nitro,

(4-19) piperidinyloxy group, optionally substituted in piperidinium ring by one or more members selected from the group consisting of lower alkyl groups; lower alkanoyl groups; benzoline groups, optionally substituted in the phenyl ring by one or more halogen atoms; and phenyl groups, optionally substituted in the phenyl ring by one or more halogen atoms,

(4-20) tetrahydropyranyl(lower)alkyl group,

(4-21) cycloalkyl(lower)al the ilen group,

(4-22) lower alkenylphenol group,

(4-23) phenyl(lower)alkyl group, optionally substituted in the alkyl group by one or more lower alkoxycarbonyl groups and optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups, optionally substituted by one or more halogen atoms, lower alkoxygroup, optionally substituted by one or more halogen atoms, and hydroxy-group,

(4-24) lower alkylenediamine phenyl(lower)alkyl group,

(4-25) furyl(lower)alkyl group,

(4-26) carbarnoyl(lower)alkyl group, optionally substituted by one or more members selected from lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups,

(4-27) lower alkoxy(lower)alkyl group,

(4-28) imidazolyl(lower)alkyl group, optionally substituted in the lower alkyl group by one or more members selected from the group consisting of carbamoyl group and lower alkoxycarbonyl groups,

(4-29) aminosilane lower alkyl group, optionally substituted by one or more lower alkyl groups,

(4-30) 2,3,4,5-tetrahydrofuryl group, optionally substituted 2,3,4,5-tertrahydrofuran ring ring one or more exography,

(4-31) the lowest alkoxycarbonyl(lower)alkyl group,

(4-32) pyrrolidinyl(lower)alkyl group, optionally substituted in the pyrolidine ring by one or more lower alkyl groups,

(4-33) phenoxy(lower)alkanoyloxy group,

(4-34) morpholino(lower)alkyl group,

(4-35) indolenine group,

(4-36) thiazolidine group,

(4-37) 1,2,4-triazolyl group,

(4-38) pyridyl(lower)alkanoyloxy group,

(4-39) taylorsville group,

(4-40) thienyl(lower)alkanoyloxy group,

(4-41) cycloalkyl(lower)alkanoyloxy group,

(4-42) isoxazolecarboxylic group, optionally substituted in isoxazoline ring by one or more lower alkyl groups,

(4-43) pyrazinecarboxamide group,

(4-44) piperidinylcarbonyl group, optionally substituted in piperidinium ring by one or more members selected from bentilee group and lower alkanoyl groups,

(4-45) chromenickel group,

(4-46) isoindoline(lower)alkanoyloxy group, optionally substituted in isoindoline the ring one or more exography,

(About 4-47) diazolidinyl(lower)alkanoyloxy group, optionally substituted in thiazolidinone ring one linescale members, selected from a carbonyl group and tocography,

(4-48) piperidinyl(lower)alkanoyloxy group,

(4-49) phenyl(lower)alkenylboronic group, optionally substituted in the phenyl ring by one or more halogen atoms,

(4-50) phenyl(lower)alkenylboronic group substituted in the phenyl ring by one or more alkylenedioxy,

(4-51) pyridyl(lower)alkenylboronic group,

(4-52) pyridylthio(lower)alkanoyloxy group,

(4-53) indolocarbazole group,

(4-54) pyrrolidinedione group,

(4-55) pyrrolidinylcarbonyl group, optionally substituted in the pyrolidine ring one or more exography,

(4-56) benzofuranyl group,

(4-57) indolyl(lower)alkanoyloxy group,

(4-58) benzothiadiazole group,

(4-59) phenyl(lower)alkanoyloxy group, optionally substituted in the phenyl ring by one or more halogen atoms,

(4-60) phenylsulfonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxycarbonyl groups; ceanography; nitro; amino groups, optionally substituted by one or more alkanolamine groups; hydroxy-group; carboxyl group; a lower alkoxycarbonyl(lower)alkyl groups; halogen atoms is; the lower alkyl groups optionally substituted by one or more halogen atoms, and lower alkoxygroup, optionally substituted by one or more halogen atoms,

(4-61) thienylmethyl group, optionally substituted in the thiophene ring by one or more members selected from the group consisting of halogen atoms and lower alkoxycarbonyl groups,

(4-62) henrylmoreno group,

(4-63) imidazolylalkyl group, optionally substituted in the imidazole ring by one or more lower alkyl groups,

(4-64) phenylsulfonyl group, optionally substituted in the phenyl ring by one or more lower alkylenedioxy,

(4-65) lower alkanesulfonyl group,

(4-66) cycloalkyl(lower)alkylsulfonyl group,

(4-67) of 3,4-dihydro-2H-1,4-benzocaineenthol group, optionally substituted in the 3,4-dihydro-2H-1,4-benzoxazinone ring by one or more lower alkyl groups,

(4-68) pyrazolylphenyl group, optionally substituted in the pyrazol ring by one or more members selected from halogen atoms and lower alkyl groups,

(4-69) isoxazolecarboxylic group, optionally substituted in isoxazoline ring by one or more lower alkyl groups,

(4-70) thiazole is sulfonyloxy group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and amino groups, and each Deputy for amino optionally substituted by one or more alkanolamine groups,

(4-71) phenyl(lower)alkylsulfonyl group,

(4-72) phenyl(lower)alkanesulfonyl group,

(4-73) naphthalocyanine group,

(4-74) lower alkyloxyalkyl group,

(4-75) lower altneratively group,

(4-76) phenyl(lower)alkoxy-substituted lower alkoxycarbonyl group,

(4-77) cycloalkylcarbonyl group, optionally substituted in cycloalkene ring by one or more lower alkyl groups,

(4-78) tetrazolyl group,

(4-79) isoxazolyl group, optionally substituted in isoxazoline ring by one or more lower alkyl groups; or

R6and R7can be connected to each other to form, together with the nitrogen atom to which they are attached, 1,2,3,4-tetrahydroisoquinoline group, isoindolyl group or a 5-7 membered saturated heterocyclic group, and heterocyclic group optionally contains one or more additional heteroatoms and optionally substituted with one to three members from the following groups (5-1)-(5-28):

p> (5-1) lower alkyl groups,

(5-2) the lower alkoxygroup,

(5-3) the carbonyl group,

(5-4) hydroxy-group,

(5-5) pyridyl(lower)alkyl groups,

(5-6) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; ceanography and hydroxy-group,

(5-7) low alkylenediamine phenyl(lower)alkyl groups,

(5-8) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more halogen atoms,

(5-9) pyrimidinium groups,

(5-10) personilnya groups,

(5-11) cycloalkyl groups,

(5-12) phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more halogen atoms,

(5-13) benzoline groups, optionally substituted in the phenyl ring by one or more halogen atoms,

(5-14) benzoline groups, substituted in the phenyl ring by one or more lower alkylenedioxy,

(5-15) carbarnoyl(lower)alkyl groups, optionally substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups,

(5-16) benzoxazolyl groups,

(5-17) lower alkoxycarbonyl groups,

(5-18) carbamoyl group,

(5-19) phenyl(lower)alkylidene groups, optionally substituted in the phenyl ring by one or more halogen atoms,

(5-20) phenyl(lower)alkoxycarbonyl groups,

(5-21) peredelnyh groups, optionally substituted in the pyridine ring by one or more members selected from the group consisting of ceanography and lower alkyl groups,

(5-22) furyl(lower)alkyl groups,

(5-23) tetrahydropyranyl groups,

(5-24) imidazolyl(lower)alkyl groups,

(5-25) naftalina groups,

(5-26) 2,3-dihydro-1H-indanilnykh groups,

(5-27) 1,3-DIOXOLANYL(lower)alkyl groups,

(5-28) groups(A3)mNR11R12;

A1represents the lowest alkylenes group;

R8and R9each independently represents one of the following substituents (6-1)-(6-25):

(6-1) a hydrogen atom,

(6-2) a lower alkyl group,

(6-3) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkylthio; lower alkoxygroup, optionally substituted by one or more halogen atoms; atoms halog is on; phenyl group; lower alkylamino; ceanography; fenoxaprop; cycloalkyl groups; pyrrolidinyl groups, optionally substituted by one or more exography; 1,2,3,4-tetrahydroisoquinolinium groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; thiazolidine groups, optionally substituted by one or more phenyl groups; carbamoyl groups; phenyl(lower)alkoxygroup; lower alkylsulfonamides; inlinegroup, optionally substituted by one or more halogen atoms; phenyl(lower)alkyl groups and replacement of the lower alkyl groups,

(6-4) cycloalkyl group,

(6-5) cycloalkyl(lower)alkyl group,

(6-6) carbarnoyl(lower)alkyl group,

(6-7) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; halogen atoms and phenyl groups,

(6-8) lower alkyls is displaced amino(lower)alkyl group,

(6-9) naftalina group,

(6-10) naphthyl(lower)alkyl group,

(6-11) tetrahydronaphthyl(lower)alkyl group,

(6-12) fluorenyl group,

(6-13) pyridyloxy group,

(6-14) pyridyl(lower)alkyl group,

(6-15) pyrimidinyl group,

(6-16) pyrazinyl(lower)alkyl group, optionally substituted in pyrazinium ring by one or more lower alkyl groups,

(6-17) thiazolidine group,

(6-18) pyrazolyl(lower)alkyl group, optionally substituted in the pyrazol ring by one or more lower alkyl groups,

(6-19) thienyl(lower)alkyl group,

(6-20) piperidinyloxy group, optionally substituted in piperidinium ring by one or more members selected from the group consisting of lower alkyl groups; bentilee group and a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups,

(6-21) indolenine group,

(6-22) indazolinone group,

(6-23) 3,4-dihydroxybutyl, optionally substituted by one or more lower alkyl groups,

(6-24) pinolillo group, optionally substituted by one or more lower alkyl groups,

(6-25) carbazolyl group, not necessarily Thames is nnow one or more lower alkyl groups; or

R8and R9can be connected to each other to form, together with the nitrogen atom to which they are attached, 5-8-membered saturated heterocyclic group optionally containing one or more additional heteroatoms and optionally substituted in the heterocyclic ring by one or more members selected from the group consisting of the following substituents (6-28-1)-(6-28-24):

(6-28-1) lower alkyl groups,

(6-28-2) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from halogen atoms and lower alkoxygroup, optionally substituted by one or more halogen atoms,

(6-28-3) naphthyl(lower)alkyl groups,

(6-28-4) phenyl(lower)allylcarbamate(lower)alkyl groups,

(6-28-5) phenylcarbamoyl(lower)alkyl groups,

(6-28-6) phenyl(lower)alkoxycarbonyl groups,

(6-28-7) phenoxy(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, optionally substituted by one or more halogen atoms,

(6-28-8) biphenylene groups,

(6-28-9) phenyl group, optionally substituted in the phenyl ring by one or more halogen atoms,

(6-28-10) 2,3-dihydroindol the x groups, optionally substituted by one or more halogen atoms,

(6-28-11) benzothiazolyl groups, optionally substituted by one or more halogen atoms,

(6-28-12) peredelnyh groups, optionally substituted by one or more halogen atoms,

(6-28-13) benzothiazoline groups,

(6-28-14) benzothiazolyl groups,

(6-28-15) thienopyridine groups,

(6-28-16) carbamoyl group,

(6-28-17) phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more halogen atoms,

(6-28-18) fenoxaprop, optionally substituted by one or more halogen atoms,

(6-28-19) benzoline groups, optionally substituted in the phenyl ring by one or more members selected from halogen atoms and lower alkoxygroup,

(6-28-20) inlinegroup, optionally substituted in the phenyl ring by one or more lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms,

(6-28-21) inlinegroup substituted in the amino group by one or more lower alkyl groups and optionally optionally substituted in the phenyl ring by one or more halogen atoms,

(6-28-22) benzoperylene groups,

(6-28-23) naftalina groups,

(6-28-24) carbonyl group; or

R8and R9 can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered unsaturated heterocyclic group, and an unsaturated heterocyclic group optionally substituted in the heterocyclic ring by one or more members selected from the group consisting of the following substituents (6-29-1)-(6-29-3):

(6-29-1) phenyl groups optionally substituted by one or more halogen atoms,

(6-29-2) 2,3-dihydroindole groups,

(6-29-3) benzothiazoline groups; or

R8and R9can be connected to each other to form, together with the nitrogen atom to which they are attached, 1,2,3,4-tetrahydroquinoline group; 1,2,3,4-tetrahydroisoquinoline group, 1,3-dihydroisoquinolines group; octahedral[1,2-a]personalni group, optionally substituted in pyrazinium ring by one or more lower alkyl groups, or 8-azabicyclo[3.2.1]octiles group, optionally substituted 8-azabicyclo[3.2.1]octiles group of one or more phenoxypropane, and each peroxisomal optionally substituted in the phenyl ring by one or more halogen atoms;

A2represents the lowest alkylenes group;

R10represents one of the following substituents (7-1)-(7-44):

(7-1) the hydrogen atom is,

(7-2) a lower alkyl group,

(7-3) alkoxycarbonyl group, optionally substituted by one or more halogen atoms,

(7-4) benzoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; phenyl groups; halogen atoms; ceanography; fenoxaprop; lower alkoxycarbonyl groups; parasailing groups and lower alkoxygroup, optionally substituted by one or more halogen atoms,

(7-5) alkanoyloxy group,

(7-6) phenyl(lower)alkanoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups,

(7-7) cycloalkyl(lower)alkanoyloxy group,

(7-8) phenyl group, optionally substituted in the phenyl ring by one or more lower alkyl groups,

(7-9) phenoxy(lower)alkanoyloxy group, optionally substituted in the phenyl ring by one or more halogen atoms,

(7-10) phenyl(lower)alkenylboronic group,

(7-11) pyridylcarbonyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halo atoms is Jena and lower alkyl groups, moreover, each lower alkyl substituent optionally substituted by one or more halogen atoms,

(7-12) fuelleborni group,

(7-13) taylorsville group,

(7-14) piperidinylcarbonyl group, optionally substituted in piperidinium ring by one or more lower alkanolamine groups,

(7-15) pyrrolidinylcarbonyl group, optionally substituted in the pyrolidine ring one or more exography,

(7-16) tetrahydropyranyloxy group,

(7-17) afterburning group,

(7-18) indolocarbazole group,

(7-19) benzofuranyl group,

(7-20) benzothiadiazole group, optionally substituted in benzothiophenes the ring one or more atoms of halogen,

(7-21) furyl(lower)alkyl group,

(7-22) pyridyl(lower)alkyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms,

(7-23) thienyl(lower)alkyl group, optionally substituted thiophene in the ring one or more atoms of halogen,

(7-24) phenyl(lower)alkyl group, optionally substituted in the phenyl ring one the or more members, selected from the group consisting of lower alkoxygroup, optionally substituted by one or more halogen atoms; ceanography; lower alkyl groups optionally substituted by one or more halogen atoms; amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups; halogen atoms; lower alkoxycarbonyl groups; lower alkanoyloxy; lower alkylsulfonyl groups; lower alkylthio and pyrrolidinyl groups,

(7-25) thiazolyl(lower)alkyl group,

(7-26) imidazolyl(lower)alkyl group, optionally substituted in the imidazole ring by one or more lower alkyl groups,

(7-27) pyrrolyl(lower)alkyl group, optionally substituted in the pyrrole ring by one or more lower alkyl groups,

(7-28) cycloalkyl(lower)alkyl group,

(7-29) lower alkylthio(lower)alkyl group,

(7-30) phenoxycarbonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxygroup,

(7-31) phenyl(lower)alkoxycarbonyl group, optionally substituted in the phenyl ring by one or more atoms halog is on,

(7-32) naphthalocyanine group,

(7-33) lower alkyloxyalkyl group,

(7-34) cycloalkylcarbonyl group,

(7-35) hinoklidilkarbinola group,

(7-36) group-CO-NR13R14,

(7-37) piperidinyloxy group, optionally substituted in piperidinium ring by one or more lower alkyl groups,

(7-38) cycloalkyl group,

(7-39) tetrahydropyranyloxy group,

(7-40) lower alkoxy(lower)alkyl group,

(7-41) tetrahydro-2H-cipirello group,

(7-42) naftalina group,

(7-43) biphenylene group,

(7-44) lower alkylsilane(lower)alkoxycarbonyl group;

A3represents the lowest alkylenes group;

m is 0 or 1;

R11and R12each independently represents one of the following substituents (8-1)to(8-5):

(8-1) a hydrogen atom,

(8-2) a lower alkyl group,

(8-3) lower alkanoyloxy group,

(8-4) phenyl(lower)alkanoyloxy group,

(8-5) phenyl group, optionally substituted in the phenyl ring by one or more halogen atoms; or

R11and R12can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic group optionally containing one or more additional heteroatoms, moreover, the heterocyclic group is optionally substituted one to three members, selected from the group consisting of the following substituents (9-1) and (9-2):

(9-1) lower alkyl groups,

(9-2) phenyl group; and

R13and R14each independently represents one of the following substituents (10-1)to(10-3):

(10-1) a hydrogen atom,

(10-2) a lower alkyl group,

(10-3) phenyl group, or

R13and R14can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic group optionally containing one or more additional heteroatoms.

Paragraph 2. Carbocyanine compound or its salt according to claim 1 wherein the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond, and each of R4and R5represents a hydrogen atom.

Item 3. Carbocyanine compound or its salt according to paragraph 2, where a group of the formula

where R3A and X are as defined above in paragraph 1, attached in position 3, 4, 5, 6, 7 or 8 barbastelle skeleton.

Item 4. Carbocyanine compound or its salt according to paragraph 3, where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond, and a group of the formula

where R3A and X are as defined above in which the unkt 1, attached in position 5 or 6 barbastelle skeleton.

Paragraph 5. Carbocyanine compound or its salt according to item 3 or 4, where A is a lower alkylenes group or lower alkylidene group.

Item 6. Carbocyanine compound or its salt according to paragraph 5, where R1represents one of the substituents (1-2), (1-3), (1-4), (1-6), (1-10), (1-12), (1-13), (1-18) and (1-21)as defined above in paragraph 1.

Item 7. Carbocyanine compound or its salt according to paragraph 6, where a group of the formula

where R3A and X are as defined above in paragraph 1, attached in position 5 barbastelle skeleton.

Item 8. Carbocyanine compound or its salt according to paragraph 7, where R1is a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of phenyl rings, halogen atoms, groups(B)lNR6R7where B, l, R6and R7are as defined in paragraph 1, the lower alkoxycarbonyl groups and phenyl(lower)alkoxygroup.

Item 9. Carbocyanine compound or its salt according to paragraph 8, where A is a lower alkylenes group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X Ave is dstanley an oxygen atom or a sulfur atom.

Paragraph 10. Carbocyanine compound or its salt according to paragraph 7, where A is a lower alkylenes group, R1represents a lower alkyl group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

Paragraph 11. Carbocyanine compound or its salt according to paragraph 7, where A is a lower alkylenes group, R1represents naphthyl(lower)alkyl group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

Item 12. Carbocyanine compound or its salt according to paragraph 7, where A is a lower alkylenes group, R1represents a group of the formula

where R10and A2are as defined above in paragraph 1, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

Paragraph 13. Carbocyanine compound or its salt according to paragraph 3, where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and a group of the formula

where 3A and X are as defined above in paragraph 1, attached in position 3, 4 or 5 barbastelle skeleton.

Paragraph 14. Carbocyanine compound or its salt according to item 13, where R1represents one of the substituents (1-2) and (1-3)as defined in paragraph 1.

Paragraph 15. Carbocyanine compound or its salt according to paragraph 14, where A represents a lower alkylenes group or lower alkylidene group, and R2represents a hydrogen atom or a lower alkoxygroup.

Paragraph 16. Carbocyanine compound or its salt according to claim 1 wherein the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and R4and R5connected to each other in the form of a group-CH=CH-CH=CH-.

Paragraph 17. Carbocyanine compound or its salt according to paragraph 16, where a group of the formula

where R3A and X are as defined above in paragraph 1, attached in position 7 barbastelle skeleton.

Paragraph 18. Carbocyanine compound or its salt according to paragraph 17, where R1represents one of the substituents (1-2) and (1-3)as defined above in paragraph 1.

Paragraph 19. Carbocyanine compound or its salt according to paragraph 18, where A is a lower alkylenes group or lower alkylidene group, R2and R3both represent hydrogen atoms, and X p is ecstasy an oxygen atom or a sulfur atom.

Paragraph 20. Carbocyanine compound or its salt according to claim 1 wherein A represents a direct connection.

Paragraph 21. Carbocyanine compound or its salt according to claim 1 wherein A represents a lower alkylenes group.

Paragraph 22. Carbocyanine compound or its salt according to paragraph 1, where a is a lower alkylidene group.

Paragraph 23. Carbocyanine compound or its salt according to any one of items 20 to 22, where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond, and each of R4and R5represents a hydrogen atom.

Paragraph 24. Carbocyanine compound or its salt according to any one of items 20 to 22, where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and R4and R5connected to each other in the form of a group-CH=CH-CH=CH-.

Paragraph 25. Carbocyanine a compound selected from the group consisting of the following compounds:

5-[1-(biphenyl-4-ylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(4-Chlorobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(4-bromobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(2-naphthylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-{1-[4-(heptyloxybiphenyl)Ben who yl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

5-[1-(1-biphenyl-4-reparacin-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-{1-[1-(4-were)piperidine-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

5-{1-[4-(2-chlorobenzenesulfonamide)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

1-(biphenyl-4-ylmethyl)-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-methyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-(3-methylbutyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

1-propyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

1-isobutyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-phenethyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-she

1-(4-phenylthiomethyl)benzyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it; or their salts.

Paragraph 26. Pharmaceutical composition containing as an active ingredient carbocyanine compound or its salt according to item 1.

Paragraph 27. Preventive and/or therapeutic agent used in the disorder, which improves the regulation of TFF has a preventive and/or therapeutic effect, comprising as active components is carbocyanine compound or its salt according to item 1.

Paragraph 28. Preventive and/or therapeutic agent according to paragraph 27, where disorder that increases regulation of TFF has a preventive and/or therapeutic effect, is a disease of the digestive tract, disease of the oral cavity, the disease of the upper respiratory tract, respiratory disease, eye disease, cancer, or wound.

Paragraph 29. Preventive and/or therapeutic agent according to paragraph 27, where disorder that increases regulation of TFF has a preventive and/or therapeutic effect, is an ulcer caused by the drug, peptic ulcer, ulcerative colitis, Crohn's disease, enteritis, caused by the drug, ischemic colitis, irritable bowel syndrome, ulcer developed after endoscopic diakonale, acute gastritis, chronic gastritis, reflux esophagitis, esophageal ulcer syndrome Beretta, gastrointestinal mucositis, hemorrhoidal disease, disease, Sjogren syndrome, xerostomia, rhinitis, pharyngitis, bronchial asthma chronic obstructive pulmonary disease, dry eye or keratoconjunctivitis.

Paragraph 30. Preventive and/or therapeutic agent according to paragraph 27, where TFF is a TFF2.

Paragraph 31. Application barbastelle compound or its salt according to paragraph 1 for profilakticheskogo and/or therapeutic agent, used when the disorder, which improves the regulation of TFF has a preventive and/or therapeutic effect.

Paragraph 32. Method of prevention and/or treatment of disorders that increase the regulation of TFF has a preventive and/or therapeutic effect, comprising the administration to a patient an effective amount of barbastelles compound or its salt according to item 1.

Paragraph 33. Preventive and/or therapeutic agent used in diseases of the digestive tract, diseases of the oral cavity, upper respiratory tract diseases, respiratory diseases, eye diseases, cancer diseases or wounds containing compound that induces the production of TFF.

Paragraph 34. Preventive and/or therapeutic agent according to item 33, where TFF is a TFF2.

Paragraph 35. The method of obtaining barbastelle connection (1) of the following formula:

or its salts, where R1, R2, R3, R4, R5, A, X, and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined in paragraph 1, including:

(i) the interaction of the compound (2) formula:

or its salts, where R1, R2, R4, R5and the relationship between the clauses 3 and 4 barbastelle skeleton I have are these, as defined above, and R15represents a hydrogen atom or a lower alkyl group, and A4represents a direct bond or lower alkylenes group,

connection (3) of the formula:

or its salt, where R3and X are as defined above, to obtain the compounds (1a) of the formula:

or its salts, where R1, R2, R3, R4, R5, R15, A4and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and

(ii) the reduction of compound (1a), as defined above, or its salt to obtain the compound (1b) of the formula:

or its salts, where R1, R2, R3, R4, R5, R15, A4and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond and a double bond, and each of R4and R5represents a hydrogen atom.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where the group of the formula

where R3And X are as defined above in paragraph 1, attached in position 3, 4, 5, 6, 7 or 8 barbastelle skeleton.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond and a group of the formula

where R3And X are as defined above in paragraph 1, attached in position 5 or 6 barbastelle skeleton.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where a is a lower alkylenes group or lower alkylidene group.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where R1represents one of the substituents (1-2), (1-3), (1-4), (1-6), (1-10), (1-12), (1-13), (1-18) and (1-21)as defined above in paragraph 1.

Among these preferred carbocyanine compounds, more preferred are compounds where the group of the formula

where R3And X are as defined above in paragraph 1, attached in position 5 barbastelle skeleton.

More preferred are compounds where R1not only is em a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from phenyl groups, halogen atoms, groups(B)lNR6R7where B, l, R6and R7are as defined above in paragraph 1, the lower alkoxycarbonyl groups and phenyl(lower)alkoxygroup, and of these carbocyanine compounds particularly preferred are compounds where a is a lower alkylenes group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where R1represents a lower alkyl group, and compounds, where a is a lower alkylenes group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom are preferable.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where R1represents naphthyl(lower)alkyl group, and compounds, where a is a lower alkylenes group, R2p is ecstasy a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom are preferable.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where R1represents a group

where R10and A2are as defined above in paragraph 1, and also preferred are compounds where a is a lower alkylenes group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and a group of the formula

where R3And X are as defined above in paragraph 1, attached in position 3, 4 or 5 barbastelle skeleton, and compounds, where R1is a Deputy (1-2) or (1-3), as defined in paragraph 1 are more preferred, and particularly preferred are specified carbodiimide connection, where a is a lower alkylenes group or lower alkali envoy group, and R 2represents a hydrogen atom or a lower alkoxygroup.

Among carbocyanine compounds represented by the General formula (1), preferred are compounds where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and R4and R5connected to each other in the form of a group-CH=CH-CH=CH-, and of these carbocyanine compounds, more preferred are compounds where the group of the formula

where R3And X are as defined above in paragraph 1, attached in position 7 barbastelle skeleton, even more preferred are compounds where R1is a Deputy (1-2) or (1-3)defined above in paragraph 1, and particularly preferred are compounds where a is a lower alkylenes group or lower alkylidene group, R2and R3both represent hydrogen atoms and X represents an oxygen atom or a sulfur atom.

Examples of particularly preferred carbocyanine compounds of the present invention are the following compounds:

5-[1-(biphenyl-4-ylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(4-Chlorobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(4-bromobenzyl)-8-m the toxi-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-[1-(2-naphthylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-{1-[4-(heptyloxybiphenyl)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

5-[1-(1-biphenyl-4-reparacin-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,

5-{1-[1-(4-were)piperidine-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

5-{1-[4-(2-chlorobenzenesulfonamide)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,

1-(biphenyl-4-ylmethyl)-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-methyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-(3-methylbutyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

1-propyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

1-isobutyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,

8-methoxy-1-phenethyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-he

1-(4-phenylthiomethyl)benzyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it.

Below are specific examples of the groups in the above formula (1).

Examples of the lower alkilinity groups include unbranched and branched C1-6alkylene group, that is their as methylene, ethylene, trimethylene, 2-metallisation, 2,2-dimethylethylene, 2,2-dimethyltrimethylene, 1-metallisation, METROTILE, utilitiles, tetramethylene, pentamethylene and hexamethylene.

Examples of the lower alkylidene groups include unbranched and branched C1-6alkylidene groups, such as methylidene, ethylidene, propylidene, butylidene, pentylidene and hexylidene.

Examples of lower alkyl groups include unbranched and branched C1-6alkyl groups such as methyl, ethyl,npropyl, isopropyl,nbutyl, isobutyl,tert-butyl,second-butyl,npencil, isopentyl, neopentyl,nhexyl, isohexyl and 3-methylpentyl.

Examples of the lower alkoxygroup include unbranched and branched C1-6alkoxygroup, such as methoxy, ethoxy,npropoxy, isopropoxy,nbutoxy, isobutoxy,tert-butoxy,second-butoxy,npentyloxy, isopentylamine, neopentylene,nhexyloxy, etexilate and 3 methylpentane.

Examples of halogen atoms include fluorine, chlorine, bromine and iodine.

Examples of the lower alkoxycarbonyl groups include alkoxycarbonyl group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as methoxycarbonyl, etoxycarbonyl,npropoxycarbonyl, isopropoxycarbonyl,nbutok carbonyl, isobutoxide,tert-butoxycarbonyl,second-butoxycarbonyl,npentyloxybenzoyl, neopentylglycol,nhexyloxybenzoyl, isohexadecane and 3-methylbenzyloxycarbonyl.

Examples of phenyl(lower)alkoxygroup include fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as benzyloxy, 2-phenylethane, 1 venlafaxi, 3 phenylpropoxy, 4-phenylbutane, 5-phenylpentane, 6-phenylhexanoic, 1,1-dimethyl-2-phenylethane and 2-methyl-3-phenylpropoxy.

Examples piperidinyl(lower)alkoxycarbonyl groups include piperidinylcarbonyl group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as

[(1-, 2-, 3 - or 4-)piperidinyl]methoxycarbonyl,

2-[(1-, 2-, 3 - or 4-)piperidinyl]etoxycarbonyl,

1-[(1-, 2-, 3 - or 4-)piperidinyl]etoxycarbonyl,

3-[(1-, 2-, 3 - or 4-)piperidinyl]propoxycarbonyl,

4-[(1-, 2-, 3 - or 4-)piperidinyl]butoxycarbonyl,

5-[(1-, 2-, 3 - or 4-)piperidinyl]pentyloxybenzoyl,

6-[(1-, 2-, 3 - or 4-)piperidinyl]hexyloxybenzoyl,

1,1-dimethyl-2-[(1-, 2-, 3 - or 4-)piperidinyl]etoxycarbonyl and

2-methyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propoxycarbonyl.

Examples cycloalkyl groups include C3-8cycloalkyl groups such as cyclo is ropel, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

Examples of amino(lower)alkoxycarbonyl groups, optionally substituted by one or more cycloalkyl groups include aminosilane alkoxycarbonyl group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted by one or two C3-8cycloalkenyl groups, such as

aminoethoxyethanol, 2-aminoethoxyethanol,

cyclopropanecarbonyl,

2-cyclohexyloxycarbonyl,

1-cyclobutanecarbonyl,

3-cyclopentylpropionyl,

4-cycloheptylmethyl,

5-cyclooctatetraene,

6-cyclohexyloxycarbonyl,

1,1-dimethyl-2-cyclohexyloxycarbonyl,

2-methyl-3-cyclopropanecarbonyl and

2-(Ncyclopropyl-Ncyclohexylamino)etoxycarbonyl.

Examples of the lower alkylthio include unbranched and branched C1-6allylthiourea, such as methylthio, ethylthio,npropylthio, isopropylthio,nbutylthio,tert-butylthio,npentylthio andnhexylthio.

Examples of 2-imidazoledicarboxylic groups, optionally substituted in the 2-imidazoline ring one or more alkylthiophene, in luchot 2-imidazoledicarbonitrile group, optionally substituted in the 2-imidazoline ring one to three lower alkylthiophene, such as

(1-, 2-, 4 - or 5-)2-imidazoledicarbonitrile,

2-methylthio-(1-, 4 - or 5-)2-imidazoledicarbonitrile,

2 ethylthio-(1-, 4 - or 5-)2-imidazoledicarbonitrile,

4 propylthio-(1-, 2 - or 5-)2-imidazoledicarbonitrile,

5-isopropylthio-(1-, 2 - or 4-)2-imidazoledicarbonitrile,

2-nbutylthio-(1-, 4 - or 5-)2-imidazoledicarbonitrile,

2-npentylthio-(1-, 4 - or 5-)2-imidazoledicarbonitrile,

2-nhexylthio-(1-, 4 - or 5-)2-imidazoledicarbonitrile,

2,4-dimethyldi-(1 - or 5-)2-imidazoledicarbonitrile and

2,4,5-trimethyltin-(1-)2-imidazoledicarbonitrile.

Examples of 3-pyrrolidinylcarbonyl groups, optionally substituted 3-pyrrolinone ring by one or more lower alkyl groups include 3-pyrrolidinylcarbonyl group, optionally substituted at the 3-pyrrolinone ring one to three lower alkyl groups, such as

(1-, 2 - or 3-)3-pyrrolidinylcarbonyl,

2-methyl-(1-, 2-, 3-, 4 - or 5-)3-pyrrolidinylcarbonyl,

2-ethyl-(1-, 2-, 3-, 4 - or 5-)3-pyrrolidinylcarbonyl,

3-propyl-(1-, 2-, 4 - or 5-)3-pyrrolidinylcarbonyl,

4-isopropyl-(1-, 2-, 3 - or 5-)3-pyrrolidinylcarbonyl,

5-nbutyl-(1-, 2-, 3-, 4 - or 5-)3-pyrrolidinylcarbonyl,

2-npentyl-(1-, 2-, 3-, 4 - or 5-)3-pyrrolidinylcarbonyl,

2-nhexyl-(1-, 2-, 3-, 4 - or 5-)3-pyrrolidinylcarbonyl,

2,5-dimethyl-(1-, 2-, 3-, 4 - Il is 5-)3-pyrrolidinylcarbonyl,

2,4-dimethyl-(1-, 2-, 3 - or 5-)3-pyrrolidinylcarbonyl,

2,3-dimethyl-(1-, 2-, 4 - or 5-)3-pyrrolidinylcarbonyl and

2,4,5-trimethyltin-(1-, 2-, 3 - or 5-)3-pyrrolidinylcarbonyl.

Examples thiazolidinediones groups, optionally substituted in thiazolidinone ring of the phenyl group include

(2-, 3-, 4 - or 5-)thiazolidinediones,

2-phenyl-(3-, 4 - or 5-)thiazolidinediones,

3-phenyl-(2-, 4 - or 5-)thiazolidinediones,

4-phenyl-(2-, 3 - and 5-)thiazolidinediones and

5-phenyl-(2-, 3 - or 4-)thiazolidinediones.

Examples piperidinyl(lower)alkyl groups include piperidinylidene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(1-, 2-, 3 - or 4-)piperidinyl]methyl,

2-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl,

1-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl,

3-[(1-, 2-, 3 - or 4-) piperidinyl]propyl,

4-[(1-, 2-, 3 - or 4-)piperidinyl]butyl,

5-[(1-, 2-, 3 - or 4-)piperidinyl]pentyl,

6-[(1-, 2-, 3 - or 4-)piperidinyl]hexyl,

1,1-dimethyl-2-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl and

2-methyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propyl.

Examples of aniline(lower)alkyl group, optionally substituted in the amino group by one or more lower alkyl groups include anilinomethylene group, optionally substituted in the amino group by one or more unbranched and/or razwell nimi C 1-6alkyl groups, such as anilinomethyl,Nmethylaminomethyl,Nethylaminomethyl,

N-n-propylaminoethyl,Nisopropylaminomethyl,

N-n-butylaminoethyl,N-Deut-butylaminoethyl,

N-tert-butylaminoethyl,N-n-pentylaniline,

N-n-hexylaniline, 2-anilinomethyl, 2-(Nmethylaniline)ethyl,

2-(Nethylaniline)ethyl, 2-(N-n-propylaniline)ethyl,

2-(Nisopropylaniline)ethyl, 2-(N-n-butylaniline)ethyl,

2-(N-Deut-butylaniline)ethyl, 2-(N-tert-butylaniline)ethyl,

2-(N-n-pentylaniline)ethyl, 2-(N-n-hexylaniline)ethyl,

3-onlinepool, 3-(Nmethylaniline)propyl,

4-(Nethylaniline)butyl, 4-(N-n-propylaniline)butyl,

5-(Nisopropylaniline)pentyl, 5-(N-n-butylaniline)pencil,

6-(N-Deut-butylaniline)hexyl, 6-(N-tert-butylaniline)hexyl,

6-(N-n-pentylaniline)hexyl and 6(N-n-hexylaniline)hexyl.

Examples of phenylthio(lower)alkyl groups include phenylthiourea group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as phenylthiomethyl, 2-phenylthiomethyl, 1-phenylthiomethyl, 3-phenylthiomethyl, 4-phenylthiomethyl, 5-phenylthiomethyl, 6-phenylthiomethyl, 1,1-dimethyl-2-phenylthiomethyl and 2-methyl-3-phenylthiomethyl.

Primaryemail(lower)alkyl groups include intrinisically group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]methyl,

2-[(1-, 2-, 3-, 4 - or 5-)indolinyl]ethyl,

1-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]ethyl,

3-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]propyl,

4-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]butyl,

5-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]pentyl,

6-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]hexyl,

1,1-dimethyl-2-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]ethyl and

2-methyl-3-[(1-, 2-, 3-, 4-, 5-, 6 - or 7)indolinyl]propyl.

Examples piperidinylcarbonyl groups, optionally substituted in piperidinium ring by one or more lower alkyl groups include piperidinylcarbonyl group, optionally substituted in piperidinium ring one to three unbranched and/or branched C1-6alkyl groups, such as (1-, 2-, 3 - or 4-)piperidinylcarbonyl,

1-methyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-ethyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-npropyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-nbutyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-npentyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-nhexyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1,2-dimethyl-(3-, 4-, 5 -, or 6-)piperidinylcarbonyl,

1,2,3-trimethyl-(4-, 5 -, or 6-)piperidinylcarbonyl,

2-npropyl-(1-, 3-, 4-, 5 -, or 6-)piperidinylcarbonyl,

3-ethyl-(1, 2-, 4-, 5 -, or 6-)piperidinylcarbonyl and

2-methyl-4-isopropyl-(1-, 3-, 5 -, or 6-)piperidinylcarbonyl.

Examples of phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of a phenyl group; lower alkyl groups; lower alkoxygroup; halogen atoms; a group -(B)lNR6R7; nitro; carboxypropyl; lower alkoxycarbonyl groups; ceanography; phenyl(lower)alkoxygroup; fenoxaprop; piperidinyl(lower)alkoxycarbonyl groups; amino(lower)alkoxycarbonyl groups, optionally substituted by one or more cycloalkyl groups; 2-imidazoledicarboxylic groups, optionally substituted in the 2-imidazoline ring by one or more lower alkylthiophene; 3-pyrrolidinylcarbonyl groups, optionally substituted in pyrrolinone ring by one or more lower alkyl groups; thiazolidinediones groups, optionally substituted in thiazolidinone ring phenyl group; 3-azabicyclo[3.2.2]noninterpolating groups; piperidinyl(lower)alkyl groups; aniline(lower)alkyl group, optionally substituted in the amino group by one or more lower alkyl groups; phenylthio(lower)alkyl groups; indolinyl(lower)alkyl groups and piperidinylcarbonyl the groups, optionally substituted in piperidinium ring by one or more lower alkyl groups include:

mono - and diphenylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of a phenyl group; the above-described non-branched and branched C1-6the alkyl groups described above unbranched and branched C1-6alkoxygroup; halogen atoms; the following groups -(B)lNR6R7; nitro group; carboxyl group; the above-described non-branched and branched C1-6alkoxycarbonyl groups; ceanography; above fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup; fenoxaprop; above piperidinylcarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup; above aminocarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted by one or two C3-8cycloalkenyl groups; the above-described 2-imidazoledicarboxylic groups, it is certainly substituted in the 2-imidazoline ring one to three unbranched and/or branched C 1-6alkylthiophene; the above 3-pyrrolidinylcarbonyl groups, optionally substituted 3-pyrrolinone ring one to three unbranched and/or branched C1-6alkyl groups; thiazolidinediones groups, optionally substituted in thiazolidinone ring phenyl group; 3-azabicyclo[3.2.2]noninterpolating groups; piperidinylidene groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group; anilinomethylene groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the amino group with one or two unbranched and/or branched C1-6alkyl groups; penaltykillah groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group; intrinisically groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, and the above-described piperidinylcarbonyl groups, optionally substituted in piperidinium ring one to three unbranched and/or branched C1-6alkyl groups;

such as benzyl, 1-phenethyl, 2-phenethyl, 3-phenylpropyl,

2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil,

6-FeNi is hexyl, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl,

1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl,

1,2-diphenylether, 4-[N(3-pyridyl)aminocarbonyl]benzyl,

4-[N(2-methoxyphenyl)aminocarbonyl]benzyl,

4-[2-(2-piperidinyl)etoxycarbonyl]benzyl,

4-[2-(cyclohexylamino)etoxycarbonyl]benzyl,

4-[4-(3-pyridylmethyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(4-pyridylmethyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-pyridylmethyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-pyridyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(3-chlorophenyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-forfinal)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-pyrimidyl)-1-piperazinylcarbonyl]benzyl,

4-(4-cyclopentyl-1-piperazinylcarbonyl)benzyl,

4-[4-(2-methoxyphenyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(4-forfinal)-1-piperazinylcarbonyl]benzyl,

4-[4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]benzyl,

4-(Ncyclohexyl-Nmethylaminomethyl)benzyl,

4-(N,N-di-nbutylaminoethyl)benzyl,

4-[4-(1-piperidinyl)-1-piperidinylcarbonyl]benzyl,

4-(1-homopiperazine)benzyl,

4-[2-methylthio-1-(2-imidazolyl)carbonyl]benzyl,

4-{N[2-(2-pyridyl)ethyl]-Nmethylaminomethyl}benzyl,

4-[N(1-methyl-4-piperidinyl)-Nmethylaminomethyl]benzyl,

4-(N,N-diisobutylamine)benzyl,

4-[N(Tetrahydropyranyl)methyl- Nethylaminomethyl]benzyl,

4-(4-thiomorpholine)benzyl,

4-[2,5-dimethyl-1-(3-pyranyl)carbonyl]benzyl,

4-(3-thiazolidinedione)benzyl,

4-(Ncyclopropylmethyl-N-n-propylaminoethyl)benzyl,

4-[1-(3-azabicyclo[3.2.2]noninterbank)benzyl,

4-(Ncyclopentyl-Narylamination)benzyl,

4-[4-(4-pyridyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(4-triptoreline)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-phenylethyl)-1-piperazinylcarbonyl]benzyl,

4-[4-(2-pyrazinyl)-1-piperazinylcarbonyl]benzyl,

4-(N-n-butylaminoethyl)benzyl,

4-(Ncyclopropanecarbonyl)benzyl,

4-[N(1-methyl-1-phenylethyl)aminocarbonyl]benzyl,

4-(Nbenzylaminocarbonyl)benzyl,

4-[N(2 Chlorobenzyl)aminocarbonyl]benzyl,

4-[N(3 chlorbenzyl)aminocarbonyl]benzyl,

4-[N(4-chlorbenzyl)aminocarbonyl]benzyl,

4-[N(2-pyridyl)methylaminomethyl]benzyl,

4-[N(3-pyridyl)methylaminomethyl]benzyl,

4-[(4-pyridyl)methylaminomethyl]benzyl,

4-[3,5-dimethyl-1-piperidinylcarbonyl]benzyl,

4-[N(2-furyl)methylaminomethyl]benzyl,

4-[4-(2-forbindelse)-1-piperidinylcarbonyl]benzyl,

4-{4-[N(2-phenylacetyl)-Nmethylamino]-1-piperidinylcarbonyl}benzyl,

4-[(4-methoxy-1-piperidinyl)carbonyl]benzyl,

4-{[4-(3,4-dimethyl-1-piperazinil)-1-piperidine is]carbonyl}benzyl,

4-{[4-(4-chlorobenzoyl)-1-piperidinyl]carbonyl}benzyl,

4-{[4-(4-Chlorobenzyl)-1-piperidinyl]carbonyl}benzyl,

4-[(4-ethylcarboxylate-1-piperidinyl)carbonyl]benzyl,

4-[(4-cyclohexyl-1-piperidinyl)carbonyl]benzyl,

4-{[4-(4-methoxyphenyl)-1-piperidinyl]carbonyl}benzyl,

4-{[4-(2-benzoxazolyl)-1-piperazinil]carbonyl}benzyl,

4-[(4-unlinkability-1-piperazinil)carbonyl]benzyl,

4-[(4-methyl-2-benzyl-1-piperazinil)carbonyl]benzyl,

4-[(4-phenyl-3-oxo-1-piperazinil)carbonyl]benzyl,

4-[(4-tert-butyl-3-oxo-1-piperazinil)carbonyl]benzyl,

4-[N(1-benzoyl-4-piperidinyl)-Nmethylaminomethyl]benzyl,

4-[N(1-acetyl-4-piperidinyl)-Nmethylaminomethyl]benzyl,

4-{[4-(4-cyanophenyl)-1-piperazinil]carbonyl}benzyl,

4-[Nmethylcarbamoylmethyl-Nbenzylaminocarbonyl]benzyl,

4-[Nbenzyl-Ncyclohexanecarbonyl]benzyl,

4-[2-(Nmethyl-Nphenylcarbamoyl)ethyl-Nmethylaminomethyl]benzyl,

4-{[4-(3-phenyl-1-pyrrolidinyl)-1-piperidinyl]carbonyl}benzyl,

4-[(1,2,3,4-tetrahydroisoquinoline-2-yl)carbonyl]benzyl,

4-[(4-benzyl-1-piperidinyl)carbonyl]benzyl,

4-{[4-(3,4-methylenedioxybenzyl)-1-piperazinil]carbonyl}benzyl,

4-[Nmethyl-N(4-methylbenzyl)aminocarbonyl]benzyl,

4-[Nmethyl-N(3,4-methylenedioxybenzyl)aminocarbonyl]benzyl,

4-[Nmethyl N(2-methoxybenzyl)aminocarbonyl]benzyl,

4-[(4-phenyl-1-piperazinil)carbonyl]benzyl,

4-[(4-phenyl-4-hydroxy-1-piperidinyl)carbonyl]benzyl,

4-(Nisopropyl-Nbenzylaminocarbonyl)benzyl,

4-(Nethyl-Ncyclohexanecarbonyl)benzyl,

4-[Nethyl-N(4-pyridyl)methylaminomethyl]benzyl,

4-(N-n-propylaminoethyl)benzyl,

4-[Nethyl-N(4-ethoxybenzyl)aminocarbonyl]benzyl,

4-(Nethyl-Ncyclohexanecarbonyl)benzyl,

4-[N(2-ethoxyethyl)aminocarbonyl]benzyl,

4-[N(1,1-dimethyl-2-phenylethyl)aminocarbonyl]benzyl,

4-[{4-[Nmethyl-N(4-chlorophenyl)amino]-1-piperidinyl}carbonyl]benzyl,

4-[N(1-methyl-1-cyclopentyl)aminocarbonyl]benzyl,

4-[N(1-methyl-1-cyclohexyl)aminocarbonyl]benzyl,

4-{N[2-(3-methoxyphenyl)ethyl]aminocarbonyl}benzyl,

4-[N(4-cryptomaterial)aminocarbonyl]benzyl,

4-{N[2-(4-chlorophenyl)ethyl]aminocarbonyl}benzyl,

4-[N(3,4-methylenedioxybenzyl)aminocarbonyl]benzyl,

4-(Ncyclohexanecarbonyl)benzyl,

4-[N(4-terbisil)aminocarbonyl]benzyl,

4-[N(1-phenylethyl)aminocarbonyl]benzyl,

4-[N(3-phenylpropyl)aminocarbonyl]benzyl,

4-{N[3-(1-imidazolyl)propyl]aminocarbonyl}benzyl,

4-[N(2-phenylethyl)aminocarbonyl]benzyl,

4-[2-(N,N-

4-{N[1-methoxycarbonyl-2-(4-hydroxyphenyl)ethyl]aminocarbonyl}benzyl,

4-[N(carbamoylmethyl)aminocarbonyl]benzyl,

4-{N[1-carbarnoyl-2-(5-imidazolyl)ethyl]aminocarbonyl}benzyl,

4-{N[1-methoxycarbonyl-2-(5-imidazolyl)ethyl]aminocarbonyl}benzyl,

4-[N(2-oxo-2,3,4,5-tetrahydrofuran-3-yl)aminocarbonyl]benzyl,

4-[(2-etoxycarbonyl-1-piperidinyl)carbonyl]benzyl,

4-(Nmethoxycarbonylmethyl-Nmethylaminomethyl)benzyl,

4-[(2-carbarnoyl-1-pyrrolidinyl)carbonyl]benzyl,

4-{[N(2,6-dimethylbenzyl)-Nethyl]aminocarbonyl}benzyl,

4-{N[(4-were)carbamoylmethyl]-Nmethylaminomethyl}benzyl,

4-[N(4-chlorbenzyl)-Nethylaminomethyl]benzyl,

4-[N(4-trifloromethyl)-Nethylaminomethyl]benzyl,

4-[N(3-bromobenzyl)-Nethylaminomethyl]benzyl,

4-{[4-(2-Chlorobenzyl)-1-piperidinyl]carbonyl}benzyl,

4-{[4-(3-Chlorobenzyl)-1-piperidinyl]carbonyl}benzyl,

4-{[4-(2-chlorobenzylidene)-1-piperidinyl]carbonyl}benzyl,

4-[N(2-methoxybenzyl)aminocarbonyl]benzyl,

4-{N[2-(2-forfinal)ethyl]aminocarbonyl}benzyl,

4-{N[2-(3-forfinal)ethyl]aminocarbonyl}benzyl,

4-[(4-benzyloxycarbonyl-1-piperazinil)carbonyl]benzyl,

4-{[4-(3-cyano-2-pyridyl)-1-piperazinil]carbonyl}benzyl,

4-[(4-phenyl-1-piperidinyl)carbonyl]benzyl,

4-[{4-[(3-furyl)methyl]-1-piperazinil}carbonyl]benzyl,

4-{[4-(3-pyridyl)-1-piperazinil]carbonyl}benzyl,

4-{[4-(4-tetrahydropyranyl)-1-piperazinil]carbonyl}benzyl,

4-{[4-(2-terbisil)-1-piperidinyl]carbonyl}benzyl,

4-{[4-(4-morpholino)-1-piperidinyl]carbonyl}benzyl,

4-{4-[2-(1,3-dioxolane-2-yl)ethyl]-1-piperazinil}carbonyl]benzyl,

4-phenylbenzyl, 2-vinylbenzyl, 3-vinylbenzyl, 4-tert-butylbenzyl, 4-aminobenzyl, 4-nitrobenzyl, 4-methoxycarbonylbenzyl,

4-carboxybenzoyl, 3-methoxy-4-Chlorobenzyl, 4-methoxybenzyl,

2,4,6-trimethoxybenzyl, 3,4-dichlorobenzyl, 4-Chlorobenzyl,

4-bromobenzyl, 2,4,6-triptorelin, 4-tormentil, 4-cyanobenzyl,

4-piperidinecarbonitrile, 4-unlinkability,

4-(Ncyclohexanecarbonyl)benzyl, 4-(Nbenzoylamine)benzyl,

4-(Ncyclohexylamino)benzyl, 4-phenylcarbonylamino,

4-methylbenzyl, 3,4-dimethylbenzyl, 3,4,5-trimethylbenzyl,

4-benzyloxybenzyl, 4-ethylcarbodiimide,

4-ethylaminoethanol, 4-isopropylaminocarbonyl,

4-[N(2-hydroxyethyl)aminocarbonyl]benzyl,

4-[N(3-pyridyl)aminocarbonyl]benzyl,

4-[N(4-chlorophenyl)aminocarbonyl]benzyl,

4-[N(4-isopropylphenyl)aminocarbonyl]benzyl,

4-[N(4-phenoxyphenyl)aminocarbonyl]benzyl,

4-[N(3-phenoxyphenyl)aminocarbonyl]benzyl,

4-[N(3 fenoc benzoyl)amino]benzyl,

4-[N(4-phenoxybenzoyl)amino]benzyl,

4-[N(4-chlorobenzoyl)amino]benzyl,

4-[N(2-chlorobenzoyl)amino]benzyl,

4-[N(2,6-dichlorobenzoyl)amino]benzyl,

4-[N(4-methoxyphenyl)aminocarbonyl]benzyl,

4-[N(2-fullcarbon)amino]benzyl,

4-[N(4-methoxybenzoyl)amino]benzyl,

4-[N(3-methoxybenzoyl)amino]benzyl,

4-[N(2-methoxybenzoyl)amino]benzyl, 4-phenoxybenzyl,

4-nventilatsioonikambri,

4-[N(4-methoxyphenethyl)amino]benzyl,

4-[N(4-methylphenoxyacetic)amino]benzyl,

4-benzyloxycarbonylamino, 4-ethanolamines,

4-(Nacetylamino)benzyl, 4-methylsulfonylbenzoyl,

methoxycarbonylaminophenyl,

4-[N(4-isopropylphenyl)aminocarbonyl]benzyl,

4-[4-{2-[(1-, 2 - or 3-)imidazolyl]ethyl}-1-piperazinylcarbonyl]benzyl,

4-{4-[3-methyl-(2-, 3 - or 4-)pyridyl]-1-piperazinylcarbonyl}benzyl,

4-{4-[4-methyl-(2-, 3 - or 4-)pyridyl]-1-piperazinylcarbonyl}benzyl,

4-[4-{2-[(2-, 3 - or 4-)pyridyl]ethyl}-1-piperazinylcarbonyl]benzyl,

4-{4-4-[(1 - or 2-)naphthyl]-(1-, 2 - or 3-)piperazinylcarbonyl}benzyl,

4-[(1-, 2-, 3 - or 4-piperazinylcarbonyl)]benzyl,

4-[2-methyl-(1-, 3-, 4-, 5 -, or 6-)piperidinylcarbonyl]benzyl,

4-[3-etoxycarbonyl-(1-, 2-, 4-, 5 -, or 6-)piperidinyl]benzyl,

4-[4-(3-hydroxyphenyl)-(1-, 2-, 4-, 5 -, or 6-)piperidinyl]benzyl,

4-[4-hydroxy-4-ensil-(1-, 2 - or 3-)piperidinylcarbonyl]benzyl,

4-[3-acetylamino-(1-, 2-, 4 - or 5-)pyrrolidinylcarbonyl]benzyl,

4-[N{2-[1-ethyl-(2 - or 3-)pyrrolidinyl]ethyl}aminocarbonyl]benzyl,

4-[N{2-[(2 - or 3-)pyrrolidinyl]ethyl}aminocarbonyl]benzyl,

4-[N{2-([2-, 3 - or 4-morpholino)ethyl}aminocarbonyl]benzyl,

4-[N{3-([2-, 3 - or 4-]morpholino)propyl}aminocarbonyl]benzyl,

4-[2,6-dimethyl-(3-, 4 - or 5-)morpholinoethyl]benzyl,

4-[4-(4-triptoreline)-(1-, 2 - or 3-)piperazinylcarbonyl]benzyl,

4-{2-[(1-, 2-, 3 - or 4-)piperidinylmethyl]-(3-, 4-, 5 -, or 6-)morpholinoethyl}benzyl,

4-(Nmethyl-N-n-intramyocardial)benzyl,

4-{4-[(1-, 2-, 4 - or 5-)2,3-dihydro-1H-indenyl]-(1-, 2 - or 3-)piperidinylcarbonyl}benzyl,

4-[N(2-methylcyclohexyl)aminocarbonyl]benzyl,

4-isoindolines,

4-[2-phenyl-(1-, 3-, 4 - or 5-)pyrrolidinylcarbonyl]benzyl,

4-{2-[(1-, 2-, 3 - or 4-morpholinomethyl)-(1-, 3-, 4 - or 5-)pyrrolidinylcarbonyl]benzyl,

4-[2-dimethylaminomethyl-(1-, 3-, 4 - or 5-)pyrrolidinylcarbonyl]benzyl,

4-{N[1-(4-perbenzoic)-(2-, 3 - or 4-)piperidinyl]-Nmethylaminomethyl}benzyl,

4-[2-phenyl-(3-, 4 - or 5-)thiazolidinediones]benzyl,

4-[Nmethyl-(2-methoxyaniline)carbonyl]benzyl,

4-(3-methylthiosemicarbazone)benzyl,

4-(2-methylthioadenosine)benzyl,

4-(3,4-dichloraniline)benzyl,

4-(4-triptoreline-anilinoacrolein)benzyl,

4-unlinkability, 4-(4-chloraniline)benzyl,

4-(4-methoxyaniline)benzyl,

4-(3-methoxyaniline)benzyl,

4-(2-chloraniline)benzyl,

4-(4-methylaminomethyl)benzyl,

4-(2,4-dimethoxyaniline)benzyl,

4-(4-methoxy-5-chloraniline)benzyl,

4-(2-methoxy-5-acetylaminofluorene)benzyl,

4-(3,4-dimethoxycinnamoyl)benzyl,

4-[2-(1-methylallyl)anilinoacrolein]benzyl,

4-(3-cryptomaterial)benzyl,

4-(2-methylaminomethyl)benzyl,

4-(2-fernlenkboot)benzyl,

4-(3-fernlenkboot)benzyl,

4-(4-fernlenkboot)benzyl,

4-(3-dimethylaminoisopropyl)benzyl,

4-(4-ethoxyaniline)benzyl,

4-(3-cryptomaterial)benzyl,

4-(4-cryptomaterial)benzyl,

4-(3-acetylaminofluorene)benzyl,

4-(4-acetylaminofluorene)benzyl,

4-[(2-, 3 - or 4-pyridylmethyl)benzyl,

4-[Nmethyl-(3-methylaniline)carbonyl]benzyl,

4-[3-methoxy-(2-, 4-, 5 -, or 6-)pyridylmethyl]benzyl,

4-(2-phenoxyalkanoic)benzyl,

4-(3-phenoxyalkanoic)benzyl,

4-(4-phenoxyalkanoic)benzyl,

4-(3,5-dichloraniline)benzyl,

4-(2,3-dimethylaminobenzoyl)benzyl,

4-(2,4-dimethylaminobenzoyl)benzyl,

4-(3,5-dimethylaniline the Nile)benzyl,

4-(3,5-differencesnational)benzyl,

4-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolylmethane]benzyl,

4-(3-fluoro-4-methoxyaniline)benzyl,

4-(4-aminosulphonylphenyl)benzyl,

4-(4-methyl-3-methoxyaniline)benzyl,

4-(3-chloro-4-methoxyaniline)benzyl,

4-(3-chloro-4-methylaminomethyl)benzyl,

4-(3-methoxy-5-cryptomaterial)benzyl,

4-(3-chloro-4-fernlenkboot)benzyl,

4-[3-methyl-(2-, 4-, 5 -, or 6-)pyridylmethyl]benzyl,

4-[(2-, 4 - or 5-thiazolidinedione)benzyl,

4-(3-chloro-4-hydroxyanthraquinones)benzyl,

4-(2-chloro-5-acetylaminofluorene)benzyl,

4-(4-methylthiosemicarbazone)benzyl,

4-(4-isopropylaminocarbonyl)benzyl,

4-(4-tert-butylaminoethyl)benzyl,

4-[(2 - or 4-)1,2,4 - triazolylmethyl]benzyl,

4-{4-[2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinyl]anilinoacrolein}benzyl,

4-(4-methylsulfonylamino)benzyl,

4-(4-methylcarbamoylmethyl)benzyl,

unlinkability, 4-(2-benzyloxycarbonyl)benzyl,

4-(4-vinylnorbornene)benzyl,

4-(4-acetylaminofluorene)benzyl,

4-(3-acetylaminofluorene)benzyl,

4-(4-cryptomaterial)benzyl,

4-{3-[(2-, 3 - or 4-)pyridyl]propionamide}benzyl,

4-(3-phenoxypropylamine)benzyl,

4-[(2-, 3 - or 4-)pyridylcarbonyl]benzyl,

<> 4-{2-[(2-, 3 - or 4-)pyridyl]acetylamino}benzyl,

4-[(2 - or 3-)fuelleborni]benzyl,

4-[(2 - or 3-)taylorsville]benzyl,

4-{2-[(2 - or 3-)thienyl]acetylamino}benzyl,

4-{2-[(1-, 2 - or 3-)pyrrolyl]-(3-, 4-, 5 -, or 6-)pyridylcarbonyl}benzyl,

4-cyclopentadienylmanganese,

4-cyclohexylcarbodiimide,

4-(2-cyclopentylacetyl)benzyl,

4-(2-cyclohexylcarbodiimide)benzyl,

4-[1-benzoyl-(2-, 3 - or 4-)piperidinylcarbonyl]benzyl,

4-[1-acetyl-(2-, 3 - or 4-)piperidinylcarbonyl]benzyl,

4-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)chromanol]benzyl,

4-(2-nitrobenzylamine)benzyl, 4-(3-nitrobenzylamine)benzyl,

4-(4-nitrobenzylamine)benzyl, 4-(2-phenylendiamine)benzyl,

4-(2-dimethylaminobenzylidene)benzyl,

4-(2-anilinomethylene)benzyl,

4-(2,6-dichloraniline)benzyl, 4-(2-cyanobenzylidene)benzyl,

4-(3-phenoxybenzamine)benzyl,

4-(2-phenoxyethylamine)benzyl,

4-(4-phenoxybenzamine)benzyl,

4-[(1 - or 2-)nattermannallee]benzyl,

4-(2-methyl-3-perbenzoate)benzyl,

4-(3,4-methylenedioxyphenethylamine)benzyl,

4-{2-[1,3-dioxo-(2-, 4 - or 5-)isoindoline]acetylamino}benzyl,

4-{2-[2-thioxo-4-oxothiazolidine]acetylamino}benzyl,

4-{3-[(1-, 2-, 3 - or 4-)piperidinyl]propionamide}benzyl,

4-(4-acetylpenicillamine)benzyl,

4-(2-triphtalocyaninine)benzyl,

p> 4-(3-triphtalocyaninine)benzyl,

4-(4-triphtalocyaninine)benzyl,

4-[2-(2-chlorophenyl)acetylamino]benzyl,

4-(2-chloro-4-perbenzoate)benzyl,

4-(2-chlorocinnamoyl)benzyl,

4-(3,4-methylenedioxyphenethylamine)benzyl,

4-[3-(2-, 3 - or 4-)pyridylcarbonyl]benzyl,

4-[2-chloro-(3-, 4-, 5 -, or 6-)pyridylcarbonyl]benzyl,

4-{2-[(2-, 3 - or 4-)pyridylthio]acetylamino}benzyl,

4-[(2-, 3-, 4-, 5-, 6 - or 7-)indolealkylamine]benzyl,

4-[(1-, 2 - or 3-)pyrrolidinedione]benzyl,

4-[2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinylcarbonyl]benzyl,

4-[(2-, 3-, 4-, 5-, 6 - or 7-)benzotrichloride]benzyl,

4-[2,6-dichloro-(3-, 4 - or 5-)pyridylcarbonyl]benzyl,

4-{2-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]acetylamino}benzyl,

4-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothiazolylsulfenamide]benzyl,

4-{4-[2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinyl]benzoylamine}benzyl,

4-{4-[(1-, 2 - or 3-)pyrrolyl]benzoylamine}benzyl,

4-{4-[(1-, 3-, 4 - or 5-)pyrazolyl]benzoylamine}benzyl,

4-{4-[(1-, 3 - or 5-)1,2,4-triazolyl]benzoylamine}benzyl,

4-{4-[(1-, 2-, 4 - or 5-)imidazolyl]benzoylamine}benzyl,

4-[4-(3,5-dimethyl-4-isoxazolyl)benzoylamine]benzyl,

4-[(2 - or 3-)pyrazinecarboxamide]benzyl,

4-(2-methoxybenzylamine)benzyl,

4-(2-methoxy-5-chlorobenzylamino)benzyl,

4-(4-chlorobenzylamino)benzyl, 4-(2-phenoxyethylamine)benzyl,

4-(3-phenylpropionyl)benzyl,

4-[(2-, 3 - or 4-)pyridylcarbonyl]benzyl,

4-benzylaminopurine, 4-innamoramento,

4-(4-methoxyphenylacetylene)benzyl,

4-(3-methoxyphenylethylamine)benzyl,

4-(2-methoxyphenylacetylene)benzyl,

4-(4-chlorophenylsulfonyl)benzyl,

4-(3-chlorophenylsulfonyl)benzyl,

4-(2-chlorophenylsulfonyl)benzyl,

4-(2-methylphenylsulfonyl)benzyl,

4-(3-methylphenylsulfonyl)benzyl,

4-(4-methylphenylsulfonyl)benzyl,

4-(4-fortunaltely)benzyl,

4-(3-fortunaltely)benzyl,

4-(2-fortunaltely)benzyl,

4-(2-methoxy-5-chlorophenylsulfonyl)benzyl,

4-(2-triftormetilfullerenov)benzyl,

4-(3-triftormetilfullerenov)benzyl,

4-(4-triftormetilfullerenov)benzyl,

4-[(2 - or 3-)teilzunehmen]benzyl,

4-(2-chlorophenylsulfonyl)benzyl,

4-(2-triftormetilfullerenov)benzyl,

4-(3-triftormetilfullerenov)benzyl,

4-(4-triftormetilfullerenov)benzyl,

4-(2-methoxycarbonylmethylene)benzyl,

4-(2-sanofisynthelabo)benzyl,

4-(3-sanofisynthelabo)benzyl,

4-(4-sanofisynthelabo)benzyl,

4-(3,4-dimethoxyphenylethylamine)benzyl,

4-(2,5-dimethoxyphenylethylamine)benzyl,

4-(2-nitro is animalporno)benzyl,

4-(3-nitrophenylacetylene)benzyl,

4-(4-nitrophenylacetylene)benzyl,

4-(4-bromophenylacetonitrile)benzyl,

4-(3-bromophenylacetonitrile)benzyl,

4-(2-bromophenylacetonitrile)benzyl,

4-(4-nbutyltrichlorosilane)benzyl,

4-(2-methoxy-5-chlorophenylsulfonyl)benzyl,

4-(2,6-dichlorophenylamino)benzyl,

4-[(1-, 2-, 3-, 4-, 5-, 6-, 7 - or 8-)chinaincorporated]benzyl,

4-[1-methyl-(2-, 4 - or 5-)imidazolidinylideneamino]benzyl,

4-(2,3-dichlorophenylamino)benzyl,

4-(2,5-dichlorophenylamino)benzyl,

4-(2,4-dichlorophenylamino)benzyl,

4-(3-nitro-4-methylphenylsulfonyl)benzyl,

4-(2-chloro-4-fortunaltely)benzyl,

4-(2,4-dichloro-5-methylphenylsulfonyl)benzyl,

4-(2-methyl-5-nitrophenylacetylene)benzyl,

4-(2-chloro-5-nitrophenylacetylene)benzyl,

4-(2-chloro-4-sanofisynthelabo)benzyl,

4-(2,4,6-trimethylphenylsulfonyl)benzyl,

4-(4-acetylbenzenesulfonyl)benzyl,

4-(3,5-dichloro-2-hydroxybenzylideneamino)benzyl,

4-(4-methoxy-2-nitrophenylacetylene)benzyl,

4-(3,4-dichlorophenylamino)benzyl,

4-(4-tert-butyltrichlorosilane)benzyl,

4-(4-carboxymethylamino)benzyl,

4-(2-bromo-5-chlorophenylsulfonyl)benzyl,

4-(4-ethylphenethylamine)benzyl,

-(2,5-dimethylsulfonium)benzyl,

4-(4-nbutoxybenzaldehyde)benzyl,

4-(2,5-differentialformen)benzyl,

4-(2-chloro-4-acetylbenzenesulfonyl)benzyl,

4-(2,4-differentialformen)benzyl,

4-(2-methoxy-4-methylphenylsulfonyl)benzyl,

4-(2-methyl-3-chlorophenylsulfonyl)benzyl,

4-(2,6-differentialformen)benzyl,

4-(3,4-differentialformen)benzyl,

4-(2-methyl-5-fortunaltely)benzyl,

4-(3-methyl-4-chlorophenylsulfonyl)benzyl,

4-(2-methyl-6-chlorophenylsulfonyl)benzyl,

4-(4-isopropylbenzenesulfonyl)benzyl,

4-(3,4-dichlorophenylamino)benzyl,

4-(2-fluoro-4-bromophenylacetonitrile)benzyl,

4-(4-methyl-3-chlorophenylsulfonyl)benzyl,

4-vinylsulfonylacetamido,

4-(3-chloropropanesulfonyl)benzyl,

4-cyclohexyldimethylamine,

4-[2-chloro-(3-, 4 - or 5-)teilzunehmen]benzyl,

4-(3,5-dichlorophenylamino)benzyl,

4-{4-[2-(4-methoxycarbonyl)ethyl]phenylcarbonylamino}benzyl,

4-[4-methyl-(2-, 3-, 4-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-dihydro-2H-1,4-benzoxazolinone]benzyl,

4-(2,2,2-cryptgethashparam)benzyl,

4-(2,3,5-trimethyl-4-methoxyphenylacetylene)benzyl,

4-[(1,3-dimethyl-5-chloro-4-pyrazolyl)sulfonylamino]benzyl,

4-[(3,5-dimethyl-4-isoxazolyl)sulfonylamino]benzyl,

4-(3-carboxy-hydroxyphenylethylamine)benzyl,

4-{[2,3-dichloro-(4 - or 5-)thienyl]sulfonylamino}benzyl,

4-{[2,5-dichloro-(3 - or 4-)thienyl]sulfonylamino}benzyl,

4-{[2-bromo-(3-, 4 - or 5-)thienyl]sulfonylamino}benzyl,

4-(4-carboxymethylamino)benzyl,

4-(2-acetylamino-4-methyl-5-thiazolecarboxamide)benzyl,

4-{[2-methoxycarbonyl-(3-, 4 - or 5-)thienyl]sulfonylamino}benzyl,

4-benzylmethylamine, 4-styrelseledamot,

4-(2,4,5-cryptorhynchinae)benzyl,

4-phenylcarbonylamino, 4-phenoxycarbonylamino,

4-[(4-chlorphenoxy)carbylamine]benzyl,

4-[(4-bromophenoxy)carbylamine]benzyl,

4-benzyloxycarbonylamino, 4-methoxycarbonylaminophenyl,

4-nbutoxycarbonylamino,

4-[(4-methoxyphenoxy)carbylamine]benzyl,

4-[(3-methoxyphenoxy)carbylamine]benzyl,

4-[(2-methoxyphenoxy)carbylamine]benzyl,

4-[(1 - or 2-)naphthalenemethylamine]benzyl,

4-[(4-pertenece)carbylamine]benzyl,

4-[(4-methylphenoxy)carbylamine]benzyl,

4-[(2-chlorobenzoyloxy)carbylamine]benzyl,

4-[2-propionylcarnitine]benzyl,

4-[(4-nitrophenoxy)carbylamine]benzyl,

4-(2-forecastable)benzyl,

4-(3-butyloxycarbonyl)benzyl,

4-(4-chlorocarbonate)benzyl,

4-(2-chlorocarbonate)benzyl,

4-[2-(benzyloxy)ethoxycarbonyl]be the ZIL,

4-propoxycarbonyl, 4-nbutoxycarbonylamino,

4-(2-isopropyl-5-methylcyclohexanecarboxylic)benzyl,

4-[(4-nitrobenzyloxy)carbylamine]benzyl,

4-(2-ethylhexylcarbonate)benzyl,

4-[Nmethyl-(4-chloroanilino)carbonyl]benzyl,

4-[(2-chloroanilino)carbonyl]benzyl,

4-[(3-cyanoaniline)carbonyl]benzyl,

4-[(4-cyanoaniline)carbonyl]benzyl,

4-[(2-cyanoaniline)carbonyl]benzyl,

4-[(2-chloro-4-foronline)carbonyl]benzyl,

4-[(1 - or 5-)tetrachlorobenzoquinone]benzyl,

4-[5-methyl-(3 - or 4-)isoxazolidinone]benzyl,

4-{4-[4-methyl-(1-, 2-, 3 - or

4-)piperazinil]anilinoacrolein}benzyl,

(2-, 3 - or 4-)(1-piperidinylmethyl)benzyl,

(2-, 3 - or 4-)(Nmethylaminomethyl)benzyl,

(2-, 3 - or 4-)(phenylthiomethyl)benzyl and

(2-, 3 - or 4-)(1-indolylmethane)benzyl.

Examples cycloalkyl(lower)alkyl groups include C3-8cycloalkylation group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as cyclopropylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 1-cyclobutylmethyl, cyclopentylmethyl, 3-cyclopentylpropionyl, 4-cyclohexylmethyl, 5-cycloheptylmethyl, 6-cyclooctylmethyl, 1,1-dimethyl-2-cyclohexylethyl and 2-methyl-3-cyclopropylmethyl.

Examples of phenoxy(lower)alkyl groups include finacial the global group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropan, 4-phenoxybutyl, 1,1-dimethyl-2-phenoxyethyl, 5-phenoxybutyl, 6-phenoxyethyl, 1-phenoxyisopropyl and 2-methyl-3-phenoxypropan.

Examples of the naphthyl(lower)alkyl groups include naphthylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as (1 - or 2-)naphthylmethyl, 2-[(1 - or 2-)naphthyl]ethyl, 1-[(1 - or 2-)naphthyl]ethyl, 3-[(1 - or 2-)naphthyl]propyl, 4-[(1 - or 2-)naphthyl]butyl, 5-[(1 - or 2-)naphthyl]pentyl, 6-[(1 - or 2-)naphthyl]hexyl, 1,1-dimethyl-2-[(1 - or 2-)naphthyl]ethyl and 2-methyl-3-[(1 - or 2-)naphthyl]propyl.

Examples of the lower alkoxy(lower)alkyl groups include alkoxyalkyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group and the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as methoxymethyl, 2-methoxyethyl, 1-ethoxyethyl, 2-ethoxyethyl, 3-nbutoxypropyl, 4-npropoxymethyl, 1-methyl-3-isobutoxide, 1,1-dimethyl-2-npentyloxide, 5-nhexyloxyphenyl, 6-methoxyphenyl, 1-ethoxyethyl and 2-methyl-3-methoxypropyl.

Examples of carboxy(lower)alkyl groups include carboxyaniline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group such as carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyethyl, 1,1-dimethyl-2-carboxyethyl and 2-methyl-3-carboxypropyl.

Examples of the lower alkoxycarbonyl(lower)alkyl groups include alkoxycarbonylmethyl group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup and alkyl fragment is an unbranched or branched C1-6alkyl group, such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 2-ethoxycarbonylethyl, 1-ethoxycarbonylethyl, 3-methoxycarbonylpropionyl, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonyl, 6-npropoxycarbonyl, 1,1-dimethyl-2-nbutoxycarbonylmethyl, 2-methyl-3-tert-butoxycarbonylmethyl, 2-nventilatsioonile andnhexyloxyphenyl.

Examples piperazinilnom groups, optionally substituted in piperazinovom ring by one or more members selected from the group consisting of phenyl groups and lower alkyl groups include:

piperazinilnom group, optionally substituted in piperazinovom ring one to three members selected and the group, consisting of phenyl groups and unbranched and branched C1-6alkyl groups; such as

(1 or 2)piperazinil,

4-methyl-(1-, 2 - or 3-)piperazinil,

4-ethyl-(1-, 2 - or 3-)piperazinil,

4-npropyl-1-, 2 - or 3-)piperazinil,

4-tert-butyl-(1-, 2 - or 3-)piperazinil,

4-second-butyl-(1-, 2 - or 3-)piperazinil,

4-nbutyl-(1-, 2 - or 3-)piperazinil,

4-npentyl-(1-, 2 - or 3-)piperazinil,

4-nhexyl-(1-, 2 - or 3-)piperazinil,

3,4-dimethyl-(1-, 2-, 5 -, or 6-)piperazinil,

3,4,5-trimethyl-(1 - or 2-)piperazinil,

4-phenyl-(1-, 2 - or 3-)piperazinil,

2,4-diphenyl-(1-, 3-, 5 -, or 6-)piperazinil,

2,3,4-triphenyl-(1-, 5 -, or 6-)piperazinil and

4-phenyl-2-methyl-(1-, 3-, 5 -, or 6-)piperazinil.

Examples of pyridylamino include (2-, 3 - or 4-)pyridylamino.

Examples of pyridylcarbonyl include (2-, 3 - or 4-)pyridylcarbonyl.

Examples of inlinegroup, optionally substituted in the amino group by one or more lower alkyl groups include inlinegroup, optionally substituted in the amino group by one or more unbranched and/or branched C1-6alkyl groups, such as aniline,Nmethylaniline,Nethylaniline,N-n-propylaniline,Nisopropylaniline,N-n-butylaniline,N-Deut-butylaniline,N-tert-butylaniline,N-n-pentylaniline andN-n hexylaniline.

Examples of pyridyl(lower)alkyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms; piperidinyl groups; morpholinopropan; piperazinilnom groups, optionally substituted in piperazinovom ring by one or more members selected from the group consisting of a phenyl group and lower alkyl group; thienyl group; phenyl group; peredelnyh groups; piperidinyl(lower)alkyl groups; phenylthio(lower)alkyl groups; biphenylene groups; lower alkyl groups optionally substituted by one or more halogen atoms; pyridylamino; pyridylcarbonyl; lower alkoxygroup; aniline(lower)alkyl group, optionally substituted in the amino group by one or more lower alkyl groups, and inlinegroup, optionally substituted in the amino group by one or more lower alkyl groups include:

pyridylamine group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the pyridine ring with one to three members selected from the group consisting of the above halogen atoms; piperidinyl groups; morpholinopropan; above piperazinilnom groups optionally substituted in piperazinovom ring one to three members, selected from the group consisting of phenyl groups and unbranched and branched C1-6alkyl group; thienyl group; phenyl group; peredelnyh groups; piperidinylidene groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group; penaltykillah groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group; biphenylene groups; lower alkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted with one to three halogen atoms; pyridylamino; pyridylcarbonyl; unbranched and branched C1-6alkoxygroup; anilinomethylene groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the amino group with one or two unbranched and/or branched C1-6alkyl groups, and the above inlinegroup, optionally substituted in the amino group by one or more unbranched and/or branched C1-6alkyl groups;

such as (2-, 3 - or 4-)pyridylmethyl,

2-[(2-, 3 - or 4-)pyridyl]ethyl, 1-[(2-, 3 - or 4-)pyridyl]ethyl,

3-[(2-, 3 - or 4-)pyridyl]propyl,

4-[(2-, 3 - or 4-)Piri is Il]butyl,

1,1-dimethyl-2-[(2-, 3 - or 4-)pyridyl]ethyl,

5-[(2-, 3 - or 4-)pyridyl]pentyl,

6-[(2-, 3 - or 4-)pyridyl]hexyl,

1-[(2-, 3 - or 4-)pyridyl]isopropyl,

2-methyl-3-[(2-, 3 - or 4-)pyridyl]propyl,

(2-chloro-3-pyridyl)methyl,

[2-chloro-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2,3-dichloro-(4-, 5 -, or 6-)pyridyl]methyl,

[2-bromo-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2,4,6-Cryptor-(3-, 5 -, or 6-)pyridyl]methyl,

[2-(1-piperidinyl)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-(4-morpholino)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-(4-methyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

2-[2-(4-ethyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]ethyl,

3-[2-(4-isopropyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]propyl,

4-[2-(4-second-butyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]butyl,

5-[2-(4-npentyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]pentyl,

6-[2-(4-nhexyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]hexyl,

[2-(4-phenyl-2-methyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-(4-phenyl-1-piperazinil)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-(3-thienyl)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-phenyl-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

2-[2,4-diphenyl-(3-, 5 -, or 6-)pyridyl]ethyl,

3-[2-(2-pyridyl)-6-(3-thienyl)-(3-, 4 - or 5-)pyridyl]propyl,

4-(3-aniline-(2-, 4-, 5 -, or 6-)pyridylmethyl,

5-[2-(4-morpholino)-(3-, 4-, 5 -, or 6-)pyridyl]pentyl,

6-[2-(1-piperidinyl)-(3-, 4-, 5 -, or 6-)pyridyl]hexyl,

[2-(2-pyridyl)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

(3-, 4-, 5 -, or 6-)(1-Piperi vinylmethyl)-2-pyridylmethyl,

(3-, 4-, 5 -, or 6-)phenylthiomethyl-2-pyridylmethyl,

(4-, 5 -, or 6-)biphenyl-3-pyridylmethyl,

(4-, 5 - or 6-trifluoromethyl-3-pyridylmethyl,

(4-, 5 -, or 6-)(2-pyridylamino)- 3-pyridylmethyl,

(4-, 5 -, or 6-)[(2 - or 3-)pyridylcarbonyl]-3-pyridylmethyl,

3,5-dimethyl-4-methoxy-2-pyridylmethyl,

(3-, 4-, 5 -, or 6-)(Nmethylaminomethyl)-2-pyridylmethyl,

[2-(Nmethylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

2-[2-(Nethylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]ethyl,

3-[2-(N-n-propylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]propyl,

4-[2-(N-n-butylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]ethyl,

5-[2-(N-n-pentylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]pentyl and

6-[2-(N-n-hexylaniline)-(3-, 4-, 5 -, or 6-)pyridyl]hexyl.

Examples of cyano(lower)alkyl groups include cyanoaniline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanomethyl, 1,1-dimethyl-2-cyanoethyl, 5-cyanophenyl, 6-cyanogenesis, 1-linosopril and 2-methyl-3-cyanopropyl.

Examples chinolin(lower)alkyl groups include hanalilolilo group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]methyl,

2-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]ethyl,

1-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)chinellato,

3-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]propyl,

4-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]butyl,

1,1-dimethyl-2-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]ethyl,

5-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]pentyl,

6-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]hexyl,

1-[(2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely]isopropyl and

2-methyl-3-[(2-, 3-, 4-, 5-, 6-, 7 - or -8)hinely]propyl.

Examples of the lower alkoxy(lower)alkoxy-substituted lower alkyl groups include alkoxyalkane alkyl groups, where each of the two alkoxy fragments represents an unbranched or branched C1-6alkoxygroup and alkyl fragment is an unbranched or branched C1-6alkyl group, such as methoxyethoxymethyl,

2-(methoxyethoxy)ethyl, 1-(ethoxyethoxy)ethyl,

3-(2-nbutoxyethoxy)propyl, 4-(3-npropoxyphene)butyl,

1,1-dimethyl-2-(4-npentyloxide)ethyl,

5-(5-nhexyloxyethoxy)pencil,

6-(6-methoxyphenoxy)hexyl, 1-ethoxyresorufin,

2-methyl-3-(2-methoxyethoxy)propyl and

3,3-dimethyl-3-(methoxyethoxy)propyl.

Examples of replacement of lower alkyl groups include unbranched and branched C1-6alkyl group substituted by one to three hydroxy groups, such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl 3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 3,3-dimethyl-3-hydroxypropyl, 2-methyl-3-hydroxypropyl and 2,3,4-trihydroxybutane.

Examples thiazolyl(lower)alkyl group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of halogen atoms, phenyl group, thienyl groups and peredelnyh groups include:

tutorialnya group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the thiazole ring with one to three members selected from the group consisting of halogen atoms, phenyl group, thienyl groups and peredelnyh groups;

such as [(2-, 4 - or 5-)thiazolyl]methyl,

2-[(2-, 4 - or 5-)thiazolyl]ethyl,

1-[(2-, 4 - or 5-)thiazolyl]ethyl,

3-[(2-, 4 - or 5-)thiazolyl]propyl,

4-[(2-, 4 - or 5-)thiazolyl]butyl,

5-[(2-, 4 - or 5-)thiazolyl]pentyl,

6-[(2-, 4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[(2-, 4 - or 5-)thiazolyl]ethyl,

[2-methyl-3-[(2-, 4 - or 5-)thiazolyl]propyl,

[2-chloro-(4 - or 5-)thiazolyl]methyl,

2-[2-chloro-(4 - or 5-)thiazolyl]ethyl,

1-[2-fluoro-(4 - or 5-)thiazolyl]ethyl,

3-[2-bromo-(4 - or 5-)thiazolyl]propyl,

4-[2-iodine-(4 - or 5-)thiazolyl]butyl,

[2-phenyl-(4 - or 5-)thiazolyl]methyl,

2-[2-phenyl-(4 - or 5-)thiazolyl]ethyl,

1-[2-phenyl-(4 - or 5-)thiazolyl]ethyl,

3-[2-phenyl-(4 - or 5-)thiazole is l]propyl,

4-[2-phenyl-(4 - or 5-)thiazolyl]butyl,

5-[2-phenyl-(4 - or 5-)thiazolyl]pentyl,

6-[2-phenyl-(4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[2-phenyl-(4 - or 5-)thiazolyl]ethyl,

[2-methyl-3-[2-phenyl-(4 - or 5-)thiazolyl]propyl,

[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]methyl,

2-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]ethyl,

1-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]ethyl,

3-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]propyl,

4-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]butyl,

5-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]pentyl,

6-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]ethyl,

[2-methyl-3-[2-(2 - or 3-)thienyl-(4 - or 5-)thiazolyl]propyl,

[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]methyl,

2-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]ethyl,

1-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]ethyl,

3-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]propyl,

4-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]butyl,

5-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]pentyl,

6-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]ethyl

and [2-methyl-3-[2-(2-, 3 - or 4-)pyridyl-(4 - or 5-)thiazolyl]propyl.

Examples of lower alkylsilane(lower)alkyl groups include alkylalkoxysilane group, where each of the two alkyl fragments represents an unbranched or branched C1-6alkyl group, that is their as trimethylsilylmethyl, (1 - or 2-)(triethylsilyl)ethyl, 3-(trimethylsilyloxy)propyl, dimethyl-tert-butylcyclohexylamine, 2-(dimethyl-tert-butylsilane)ethyl, 3-(dimethyl-tert-butylsilane)propyl, 4-(dimethyl-tert-butylsilane)butyl, 5-(dimethyl-tert-butylsilane)pentyl and 6-(dimethyl-tert-butylsilane)hexyl.

Examples of phenoxy(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; halogen atoms; lower alkenyl groups; cycloalkyl groups, nitro and phenyl groups include:

finacially group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of unbranched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; an unbranched and branched C1-6alkoxygroup; halogen atoms; an unbranched and branched C2-6alkenyl groups; C3-8cycloalkyl groups; nitro and phenyl groups;

such as 3-[(2-, 3 - or 4-)methylphenoxy]propyl,

3-[(2-, 3 - or 4-)propyl is enocsi]propyl,

3-[(2-, 3 - or 4-)methoxyphenoxy]propyl,

3-[(2,3 - or 3,4-)dichlorophenoxy]propyl,

3-[(2,3 - or 3,4-)divergence]propyl,

3-[3-fluoro-4-chlorophenoxy]propyl,

3-[(2-, 3 - or 4-)triptoreline]propyl,

3-[2-methoxy-4-propenylbenzene]propyl,

3-[2-chloro-4-methoxyphenoxy]propyl,

(2-, 3 - or 4-)cyclopentylpropionyl,

3-[(2-, 3 - or 4-)nitrophenoxy]propyl,

3-[(2,3 - or 3,4-)dimethylphenoxy]propyl and

3-[(2-, 3 - or 4-)phenyleneoxy]propyl.

Examples of phenylthio(lower)alkyl group, optionally substituted in the phenyl ring by one or more halogen atoms include:

phenylthiourea group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as phenylthiomethyl, 2-phenylthiomethyl, 1-phenylthiomethyl,

3-phenylthiomethyl, 4-phenylthiomethyl, 5-phenylthiomethyl,

6-phenylthiomethyl, 1,1-dimethyl-2-phenylthiomethyl,

2-methyl-3-phenylthiomethyl, (2-, 3 - or 4-)chlorophenylacetyl,

2-[(2-, 3 - or 4-)chlorophenylthio]ethyl,

3-[(2-, 3 - or 4-)chlorophenylthio]propyl,

4-[(2-, 3 - or 4-)forfinally]butyl,

5-[(2-, 3 - or 4-)pampanito]pentyl and

6-[(2-, 3 - or 4-)idenity]hexyl.

Examples piperidinyl(lower)alkyl group, optionally substituted in piperidinium the ring one or more members of the and, selected from the group consisting of phenyl groups and phenyl(lower)alkyl groups include:

piperidinylidene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in piperidinium ring one to three members selected from the group consisting of phenyl groups and phenylalkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group;

such as [(1-, 2-, 3 - or 4-)piperidinyl]methyl,

2-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl,

1-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl,

3-[(1-, 2-, 3 - or 4-)piperidinyl]propyl,

4-[(1-, 2-, 3 - or 4-)piperidinyl]butyl,

5-[(1-, 2-, 3 - or 4-)piperidinyl]pentyl,

6-[(1-, 2-, 3 - or 4-)piperidinyl]hexyl,

1,1-dimethyl-2-[(1-, 2-, 3 - or 4-)piperidinyl]ethyl,

2-methyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propyl,

[4-phenyl-1-piperidinyl]methyl, 3-[4-phenyl-1-piperidinyl]propyl,

[4-phenylmethyl-1-piperidinyl]methyl,

3-[4-phenylmethyl-1-piperidinyl]propyl,

2-[4-phenyl-(1-, 2 - or 3-)piperidinyl]ethyl,

3-[4-phenylmethyl-(1-, 2 - or 3-)piperidinyl]propyl,

4-[4-phenylethyl-(1-, 2 - or 3-)piperidinyl]butyl,

5-[4-phenyl-(1-, 2 - or 3-)piperidinyl]pentyl and

6-[4-phenyl-(1-, 2 - or 3-)piperidinyl]hexyl.

Examples piperazinil(lower)alkyl group, optionally substituted in piperazinovom ring is one or more phenyl groups, include:

piperazinylmethyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in piperazinovom ring with one to three phenyl groups;

such as (1 - or 2-)piperazinylmethyl,

2-[(1 - or 2-)piperazinil]ethyl,

[4-phenyl-(1-, 2 - or 3-)piperazinil]methyl,

2-[4-phenyl-(1-, 2 - or 3-)piperazinil]ethyl,

3-[4-phenyl-(1-, 2 - or 3-)piperazinil]propyl,

4-[4-phenyl-(1-, 2 - or 3-)piperazinil]butyl,

5-[4-phenyl-(1-, 2 - or 3-)piperazinil]pentyl and

6-[4-phenyl-(1-, 2 - or 3-)piperazinil]hexyl.

Examples of the 1,2,3,4-tetrahydroisoquinoline(lower)alkyl groups include 1,2,3,4-tetrahydroisoquinoline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as

(1,2,3,4-tetrahydroisoquinoline-2-yl)methyl,

2-(1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl,

3-(1,2,3,4-tetrahydroisoquinoline-2-yl)propyl,

4-(1,2,3,4-tetrahydroisoquinoline-2-yl)butyl,

5-(1,2,3,4-tetrahydroisoquinoline-2-yl)pentyl and

6-(1,2,3,4-tetrahydroisoquinoline-2-yl)hexyl.

Examples of naphthyloxy(lower)alkyl groups include naphthalocyanine group, where the alkyl fragment is an unbranched or branched C1-6alkyl group such as 1-naphthylacetyl, 2-(2-naphthyloxy)ethyl,

3-(1-naphthylacetyl, 3-(2-naphthyloxy)propyl,

4-(1-naphthyloxy)butyl, 5-(2-naphthyloxy)pencil and

6-(1-naphthyloxy)hexyl.

Examples of benzothiazolinone(lower)alkyl group, optionally substituted in benzothiazoline ring by one or more alkyl groups, include:

benzothiazolylsulfenamide group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in benzothiazolium ring one to three unbranched and/or branched C1-6alkyl groups;

such as 1-[benzothiazol-(2-,4-,5-,6 - or 7-)yloxy]methyl,

2-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]ethyl,

3-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]propyl,

3-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]propyl,

4-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]butyl,

5-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]pentyl,

6-[benzothiazol-(2-,4-,5-,6-or 7-)yloxy]hexyl,

2-methylbenzothiazol-5-intoximeter,

2-(2-methylbenzothiazol-5-yloxy)ethyl,

3-(2-methylbenzothiazol-5-yloxy)propyl,

4-(2-ethylbenzothiazoline-5-yloxy)butyl,

5-(2-ethylbenzothiazoline-5-yloxy)pentyl and

6-(2-ethylbenzothiazoline-5-yloxy)hexyl.

Examples of the lower alkyl groups substituted by one or more members selected from the group consisting of chinalanoxin and ethanolammonium include:

alkyl groups, where the alkyl fragm the t represents an unbranched or branched C 1-6alkyl group, substituted by one to three members selected from the group consisting of chinalanoxin and ethanolammonium;

such as (5-hinomisaki)methyl, 2-(5-hinomisaki)ethyl,

3-(5-hinomisaki)propyl, 4-(5-hinomisaki)butyl,

5-(5-hinomisaki)pentyl, 6-(5-hinomisaki)hexyl,

(5 athinaiki)methyl, 2-(5-athinaiki)ethyl,

3-(5-athinaiki)propyl, 4-(5-athinaiki)butyl,

5-(5-athinaiki)pentyl and 6-(5-athinaiki)hexyl.

Examples of pyridyloxy(lower)alkyl group, optionally substituted in the pyridine ring with one or more lower alkyl groups include:

pyridyloxyacetic group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the pyridine ring with one to three unbranched and/or branched C1-6alkyl groups;

such as (2-, 3 - or 4-)pyridyloxy,

2-[(2-, 3 - or 4-)pyridyloxy]ethyl,

1-[(2-, 3 - or 4-)pyridyloxy]ethyl,

3-[(2-, 3 - or 4-)pyridyloxy]propyl,

4-[(2-, 3 - or 4-)pyridyloxy]butyl,

1,1-dimethyl-2-[(2-, 3 - or 4-)pyridyloxy]ethyl,

5-[(2-, 3 - or 4-)pyridyloxy]pentyl,

6-[(2-, 3 - or 4-)pyridyloxy]hexyl,

[6-methyl-(2-, 3-, 4 - or 5-)pyridyloxy]methyl,

2-[6-ethyl-(2-, 3-, 4 - or 5-)pyridyloxy]ethyl,

3-[6-methyl-(2-, 3-, 4 - or 5-)pyridyloxy]propyl,

4-[6-methyl-(2-, 3-, 4 - or 5-)pyridyloxy]butyl,

5-[6-methyl-(2-, 3-, 4 - or 5-)pyridyloxy]pentyl and

6-[6-methyl-(2-, 3-, 4 - or 5-)pyridyloxy]hexyl.

Examples of carboxy(lower)alkoxygroup include carboxitherapy, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as carboxymethoxy, 2-carboxymethoxy, 1 carboxymethoxy, 3 carboxypropyl, 4-carboxymethoxy, 5-carboxypentyl, 6-carboxycellulose, 1,1-dimethyl-2-carboxymethoxy and 2-methyl-3-carboxypropanoyl.

Examples of the lower alkoxycarbonyl(lower)alkoxygroup include alkoxycarbonylmethyl, where each of the two alkoxy fragments represents an unbranched or branched C1-6alkoxygroup, such as ethoxycarbonylmethoxy,

ethoxycarbonylmethoxy, 2-ethoxycarbonylmethoxy,

2 ethoxycarbonylmethoxy, 1 ethoxycarbonylmethoxy,

3 methoxycarbonylpropionyl, 3 ethoxycarbonylmethoxy,

4 ethoxycarbonylmethoxy, 5-isopropoxyaniline,

6-npropoxycarbonyl,

1,1-dimethyl-2-nbutoxycarbonylamino,

2-methyl-3-tert-butoxycarbonylamino,

2-nventilatsiooniauk andnhexyloxyethoxy.

Examples of lower alkyl groups optionally substituted by one or more halogen atoms, vklyuchayutsya and branched C 1-6alkyl group, optionally substituted with one to three halogen atoms, such as, in addition to the above-described lower alkyl groups, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 4,4,4-tripcomputer, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl and 5,6-dibromohexane.

Examples of the lower alkylthio, optionally substituted by one or more halogen atoms include unbranched and branched C1-6allylthiourea, optionally substituted with one to three halogen atoms, such as, in addition to the above-described lower alkylthiol, triptoreline, trichloromethylthio, chlorotri, brometalia, formailty, idetity, deformality, Diplomatico, 2-chloroethylthio, 2,2,2-triptoreline, 2,2,2-trichloromethylthio, 3 chlorpropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutylene, 4-formality, 4,4,4-cryptosporidia, 5-chlorinity, 3-chloro-2-methylpropyl, 5-Bromhexine and 5,6-dibromohexane.

Examples of the lower alkylsulfonyl groups include unbranched and branched C1-6alkylsulfonyl group, optionally substituted with one to three halogen atoms, such as methylsulphonyl, ethylsulfonyl,npropylsulfonyl is, isopropylphenyl,nbutylsulfonyl, isobutylphenyl,tert-butylsulfonyl,second-butylsulfonyl,npeterculter, isopentylamine, neopentylene,nhexylsilane, isohexanol and 3-methylphenylsulfonyl.

Examples of phenyl(lower)alkenyl groups include phenylalkylamine group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, such as styryl, 3-phenyl-2-propenyl (trivial name: cinnamyl), 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3-hexenyl, 4-phenyl-1,3-butadienyl and 6-phenyl-1,3,5-hexatriene.

Examples of the lower alkanoyloxy include unbranched and branched C2-6alkanoyloxy, such as atomic charges, propionyloxy, butyryloxy, isobutyryloxy, pentanoate,tert-BUTYLCARBAMATE, hexanoate.

Examples of phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkylthio, optionally substituted by one or more halogen atoms; lower alcohol is a system of groups; nitro; lower alkylsulfonyl groups; lower alkoxycarbonyl groups; phenyl(lower)alkenyl groups; lower alkanoyloxy and 1,2,3-thiadiazolyl groups include:

fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above halogen atoms; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkylthio, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkoxygroup; nitro; above unbranched and branched C1-6alkylsulfonyl groups; the above-described non-branched and branched C1-6alkoxycarbonyl groups; the above-described fenilalanina groups containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group; the above-described non-branched and branched C1-6alkanoyloxy and 1,2,3-thiadiazolyl groups;

such as benzyloxy, 2-phenylethane, 1 venlafaxi,

3-phenyl what robaxi, 4 phenylmethoxy, 5-phenylpentane,

6 phenylhexanoic, 1,1-dimethyl-2-phenylethane,

2-methyl-3-phenylpropoxy, 4-chlorobenzoyloxy, 2-chlorobenzoyloxy,

3 Chlorobenzilate, 3 fermentelos, 4-forbindelse,

2,4-dibromobenzoate, 2,4,6-triptoreline,

3 triftormetilfosfinov, 4-triftormetilfosfinov,

4 methylbenzylamine, 3 methylbenzylamine, 2,4-dimethylbenzylamine,

2,4,6-trimethylbenzene, 4-methoxycarbonylbenzyl,

3 methoxybenzyloxy, 2-methoxybenzyloxy,

3 methoxycarbonylbenzyl, 2,3-dimethoxybenzoate,

2,4,5-trimethoxybenzoic, 3 nitrobenzyloxy,

2-(2,3-dinitrophenyl)ethoxy, 3-(2,4,6-trinitrophenyl)ethoxy,

2-nitro-4-methylbenzylamine, 4-methylsulfonylbenzoyl,

4-(4-ethylsulfonyl)butoxy,

5-(4-propylsulfonyl)pentyloxy, 4-acetyloxybenzoic,

6-(4-propionyloxy)hexyloxy, 4-streventname,

4-(1,2,3-thiadiazole-4-yl)benzyloxy, 4-triftormetilfosfinov,

3 methylthioribose, 2,4-dimethylthiazole and

2,4,6-trimethylsiloxy.

Examples piperidinyl(lower)alkoxygroup, optionally substituted in piperidinium ring by one or more lower alkyl groups include:

piperidinecarboxylate, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, not necessarily nesennye in piperidinium ring one to three unbranched and/or branched C 1-6alkyl groups;

such as [(1-, 2-, 3 - or 4-)piperidinyl]methoxy,

2-[(1-, 2-, 3 - or 4-)piperidinyl]ethoxy,

1-[(1-, 2-, 3 - or 4-)piperidinyl]ethoxy,

3-[(1-, 2-, 3 - or 4-)piperidinyl]propoxy,

4-[(1-, 2-, 3 - or 4-)piperidinyl]butoxy,

5-[(1-, 2-, 3 - or 4-)piperidinyl]pentyloxy,

6-[(1-, 2-, 3 - or 4-)piperidinyl]hexyloxy,

1,1-dimethyl-2-[(1-, 2-, 3 - or 4-)piperidinyl]ethoxy,

2-methyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propoxy,

[1-methyl-(2-, 3 - or 4-)piperidinyl]methoxy,

2-[1-ethyl-(2-, 3 - or 4-)piperidinyl]ethoxy,

3-[1-npropyl-(2-, 3 - or 4-)piperidinyl]propoxy,

4-[1-nbutyl-(2-, 3 - or 4-piperidinyl)butoxy,

5-[1-npentyl-(2-, 3 - or 4-)piperidinyl]pentyloxy,

6-[1-nhexyl-(2-, 3 - or 4-)piperidinyl]hexyloxy,

[1,2-dimethyl-(3-, 4-, 5 -, or 6-)piperidinyl]methoxy,

[1,2,3-trimethyl-(4-, 5 -, or 6-)piperidinyl]methoxy,

2-[2-npropyl-(3-, 4-, 5 -, or 6-)piperidinyl]ethoxy,

2-[3-ethyl-(2-, 4-, 5 -, or 6-)piperidinyl]ethoxy and

[2-methyl-4-isopropyl-(3-, 5 - or 6-piperidinyl)methoxy.

Examples aminosilane lower alkoxygroup, optionally substituted in each amino group of one or more lower alkyl groups include aminosilane unbranched and branched C1-6alkoxygroup, optionally substituted in the amino group with one or two unbranched and/or branched C1-6alkyldimethyl, such as aminoethoxy,

2 aminoethoxy, 1 aminoethoxy, 3 aminopropoxy, 4-aminobutoxy,

5-aminopentanoic, 6-aminohexyl, 1,1-dimethyl-2-aminoethoxy,

2-methyl-3-aminopropoxy, methylaminomethyl, 1 ethyleneoxy,

2-npropylaminoethyl, 3 isopropylidenedioxy,

4-nbutylaminoethyl, 5-nintellinetics,

6-nexelonexelon, dimethylaminoethoxy,

3 dimethylaminopropoxy, 2-diisopropylaminoethanol,

(Nethyl-N-n-propylamino)methoxy and

2-(Nmethyl-N-n-hexylamino)ethoxy.

Examples of the lower alkenylacyl include unbranched and branched C2-6alkenylacyl containing one to three double bonds, such as vinyloxy, 1 propenyloxy,

1-methyl-1-propenyloxy, 2-methyl-1-propenyloxy, 2-propenyloxy,

2 butenyloxy, 1 butenyloxy, 3 butenyloxy, 2-pentyloxy,

1 pentyloxy, 3 pentyloxy, 4-pentyloxy,

1,3-butadienyl, 1,3-pentadienyl, 2-penten-4-yloxy,

2 hexenoate, 1 hexenoate, 5-hexenoate, 3 hexenoate,

4 hexenoate, 3,3-dimethyl-1-propenyloxy,

2-ethyl-1-propenyloxy, 1,3,5-hexatriene,

1,3-hexadiene and 1,4-hexadiene.

Examples of pyridyl(lower)alkoxygroup, optionally substituted in the pyridine ring with one or more lower alkyl groups, etc is what each lower alkyl substituent optionally substituted by one or more halogen atoms, include:

pyridyloxy, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the pyridine ring with one to three above unbranched and/or branched C1-6alkyl groups, each alkyl substituent optionally substituted with one to three halogen atoms;

such as [(2-, 3 - or 4-)pyridyl]methoxy,

2-[(2-, 3 - or 4-)pyridyl]ethoxy,

1-[(2-, 3 - or 4-)pyridyl]ethoxy,

3-[(2-, 3 - or 4-)pyridyl]propoxy,

4-[(2-, 3 - or 4-)pyridyl]butoxy,

5-[(2-, 3 - or 4-)pyridyl]pentyloxy,

6-[(2-, 3 - or 4-)pyridyl]hexyloxy,

1,1-dimethyl-2-[(2-, 3 - or 4-)pyridyl]ethoxy,

2-methyl-3-[(2-, 3 - or 4-)pyridyl]propoxy,

[2-trifluoromethyl-(3-, 4-, 5 -, or 6-)pyridyl]methoxy,

[2-methyl-(3-, 4-, 5 -, or 6-)pyridyl]methoxy,

[2,4-dimethyl-(3-, 5 -, or 6-)pyridyl]methoxy,

[2,4,6-trimethyl-(3 - or 5-)pyridyl]methoxy),

[2-trifluoromethyl-4-methyl-(3-, 5 -, or 6-)pyridyl]methoxy,

2-[3-ethyl-(2-, 4-, 5 -, or 6-)pyridyl]ethoxy,

3-[4-npropyl-(2 - or 3-)pyridyl]propoxy,

4-[3-nbutyl-(2-, 4-, 5 -, or 6-)pyridyl]butyl,

5-[3-trifluoromethyl-(2-, 4-, 5 -, or 6-)pyridyl]pentyloxy,

6-[2-npentyl-(3-, 4-, 5 -, or 6-)pyridyl]hexyloxy and

[2-nhexyl-(3-, 4-, 5 -, or 6-)pyridyl]methoxy.

Examples of the lower alkyloxy include unbranched and branched C2-6Alki is lexigraphy, such as adenylate, 2-propenyloxy, 2-butenyloxy, 3 butenyloxy, 1-methyl-2-propenyloxy, 2-pentyloxy and 2 hexyloxy.

Examples of phenyl(lower)alkyloxy include phenylaminopropyl, where alkyloxy-fragment represents an unbranched or branched C2-6alkyloxy, such as 2-phenylacrylate, 3-phenyl-2-propenyloxy, 4-phenyl-2-butenyloxy, 4-phenyl-3-butenyloxy, 3-phenyl-1-methyl-2-propenyloxy, 5-phenyl-2-pentyloxy and 6-phenyl-2-hexyloxy.

Examples of phenyl(lower)alkenylacyl include phenylalkylamine containing one to three double bonds, where alkenylacyl-fragment represents an unbranched or branched C2-6alkenylacyl, such as sterilox,

3-phenyl-1-propenyloxy, 3-phenyl-1-methyl-1-propenyloxy,

3-phenyl-2-methyl-1-propenyloxy, 3-phenyl-2-propenyloxy,

4-phenyl-2-butenyloxy, 4-phenyl-1-butenyloxy,

4-phenyl-3-butenyloxy, 4-phenyl-2-pentyloxy,

5-phenyl-1-pentyloxy, 5-phenyl-3-pentyloxy,

5-phenyl-4-pentenoate, 4-phenyl-1,3-butadienyl,

5-phenyl-1,3-pentadienyl, 5-phenyl-2-penten-4-yloxy,

6-phenyl-2-hexenoate, 6-phenyl-1-hexenoate,

6-phenyl-5-hexenoate, 6-phenyl-3-hexenoate,

6-phenyl-4-hexenoate, 3-phenyl-3,3-dimethyl-1-propenyloxy,

3-phenyl-2-ethyl-1-propenyloxy, 6-phenyl-1,3,5-hexatriene,

6-enyl-1,3-hexadiene and 6-phenyl-1,4-hexadiene.

Examples furyl(lower)alkoxygroup, optionally substituted in the furan ring by one or more lower alkoxycarbonyl groups include:

fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the furan ring with one to three above alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup;

such as [(2 - or 3-)furyl]methoxy, 2-[(2 - or 3-)furyl]ethoxy,

1-[(2 - or 3-)furyl]ethoxy, 3-[(2 - or 3-)furyl]propoxy,

4-[(2 - or 3-)furyl]butoxy, 5-[(2 - or 3-)furyl]pentyloxy,

6-[(2 - or 3-)furyl]hexyloxy,

1,1-dimethyl-2-[(2 - or 3-)furyl]ethoxy,

2-methyl-3-[(2 - or 3-)furyl]propoxy,

[2-etoxycarbonyl-(3-, 4 - or 5-)furyl]methoxy,

[2-methoxycarbonyl-(3-, 4 - or 5-) furyl]methoxy,

[3-npropoxycarbonyl-(2-, 4 - or 5-)furyl]methoxy,

[2-nbutoxycarbonyl-(3-, 4 - or 5-)furyl]methoxy,

[3-npentyloxybenzoyl-(2-, 4 - or 5-)furyl]methoxy,

[2-nhexyloxybenzoyl-(3-, 4 - or 5-)furyl]methoxy,

[2,3-dietoksikarbonil-(4 - or 5-)furyl]methoxy,

2,3,4-trimethoxybenzoyl-5-furyl)methoxy,

2-[3-npropoxycarbonyl-(2-, 4 - or 5-)furyl]ethoxy,

3-[2-nbutoxycarbonyl-(3-, 4 - or 5-)furyl]propoxy,

4-[3-npentile dicarbonyl-(2-, 4 - or 5-)furyl]butoxy,

5-[2-nhexyloxybenzoyl-(3-, 4 - or 5-)furyl]pentyloxy and

6-[2-nhexyloxybenzoyl-(3-, 4 - or 5-)furyl]hexyloxy.

Examples tetrazolyl(lower)alkoxygroup, optionally substituted in tetrazolium ring one member selected from the group consisting of phenyl groups, a phenyl(lower)alkyl groups and cycloalkyl(lower)alkyl groups include:

TetraSociology, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in tetrazolium ring one member selected from the group consisting of phenyl groups described above phenylalkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, and the above C3-8cycloalkenyl groups, where the alkyl fragment is an unbranched or branched

C1-6alkyl group;

such as [(1 - or 5-)tetrazolyl]methoxy,

2-[(1 - or 5-) tetrazolyl]ethoxy,

1-[(1 - or 5-)tetrazolyl]ethoxy,

3-[(1 - or 5-)tetrazolyl]propoxy,

4-[(1 - or 5-)tetrazolyl]butoxy,

5-[(1 - or 5-)tetrazolyl]pentyloxy,

6-[(1 - or 5-)tetrazolyl]hexyloxy,

1,1-dimethyl-2-[(1 - or 5-)tetrazolyl]ethoxy,

2-methyl-3-[(1 - or 5-)tetrazolyl]propoxy,

(1-benzyl-5-tetrazolyl)methoxy, (1-f the Nile is a 5-tetrazolyl)methoxy,

(1-cyclohexylmethyl-5-tetrazolyl)methoxy,

[5-(2-phenylethyl)-1-tetrazolyl]methoxy,

[1-(1-phenylethyl)-5-tetrazolyl]methoxy,

[1-(3-phenylpropyl)-5-tetrazolyl]methoxy,

[5-(4-phenylbutyl)-1-tetrazolyl]methoxy,

[1-(5-fenilpentil)-5-tetrazolyl]methoxy,

[1-(6-phenylhexa)-5-tetrazolyl]methoxy,

[5-(2-cyclohexylethyl)-1-tetrazolyl]methoxy,

[1-(1-cyclopropylethyl)-5-tetrazolyl]methoxy,

[1-(3-cyclobutylmethyl)-5-tetrazolyl]methoxy,

[5-(4-cyclopentylmethyl)-1-tetrazolyl]methoxy,

[1-(5-cycloheptylmethyl)-5-tetrazolyl]methoxy,

[1-(6-cyclooctylmethyl)-5-tetrazolyl]methoxy,

2-(1-phenyl-5-tetrazolyl)ethoxy,

3-(1-cyclohexylmethyl-5-tetrazolyl)propoxy,

4-[5-(2-phenylethyl)-1-tetrazolyl]butoxy,

5-(1-benzyl-5-tetrazolyl)pentyloxy,

6-(1-phenyl-5-tetrazolyl)hexyloxy and

1-(1-cyclohexylmethyl-5-tetrazolyl)ethoxy.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more lower alkyl groups include phenyl group, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkyl groups, such as phenyl, 2-were, 3-were, 4-were 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-nbutylphenyl, 4-npentylphenol, 4-nhexylphenyl, 3,4-dimetilfenil, 3,4-diethylphenyl, 2,4-DIMET lpanel, 2,5-dimetilfenil, 2,6-dimetilfenil and 3,4,5-trimetilfenil.

Examples of 1,2,4-oxadiazolyl(lower)alkoxygroup, optionally substituted in 1,2,4-oxadiazole ring of the phenyl group, and a phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups include:

1,2,4-oxadiazolidine, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in 1,2,4-oxadiazole ring one of the above described phenyl groups, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkyl groups;

such as [(3 - or 5-)1,2,4-oxadiazolyl]methoxy,

2-[(3 - or 5-)1,2,4-oxadiazolyl]ethoxy,

1-[(3 - or 5-) 1,2,4-oxadiazolyl]ethoxy,

3-[(3 - or 5-)1,2,4-oxadiazolyl]propoxy,

4-[(3 - or 5-)1,2,4-oxadiazolyl]butoxy,

5-[(3 - or 5-) 1,2,4-oxadiazolyl]pentyloxy,

6-[(3 - or 5-)1,2,4-oxadiazolyl]hexyloxy,

1,1-dimethyl-2-[(3 - or 5-)1,2,4-oxadiazolyl]ethoxy,

2-methyl-3-[(3 - or 5-)1,2,4-oxadiazolyl]propoxy,

[3-(4-tert-butylphenyl)-5-1,2,4-oxadiazolyl]methoxy,

[3-(3-were)-5-1,2,4-oxadiazolyl]methoxy,

[5-(2-ethylphenyl)-3-1,2,4-oxadiazolyl]methoxy,

[3-(4-npropylphenyl)-5-1,2,4-oxadiazolyl]methoxy,

[5-(3-npentylphenol)-3-1,2,4-oxadiazolyl]metox is,

[3-(2-nhexylphenyl)-5-1,2,4-oxadiazolyl]methoxy,

[3-(2,4-dimetilfenil)-5-1,2,4-oxadiazolyl]methoxy,

[3-(2,3,5-trimetilfenil)-5-1,2,4-oxadiazolyl]methoxy,

2-[3-(4-tert-butylphenyl)-5-1,2,4-oxadiazolyl]ethoxy,

1-[3-(3-were)-5-1,2,4-oxadiazolyl]ethoxy,

3-[5-(2-ethylphenyl)-3-1,2,4-oxadiazolyl]propoxy,

4-[3-(4-npropylphenyl)-5-1,2,4-oxadiazolyl]butoxy,

5-[5-(3-npentylphenol)-3-1,2,4-oxadiazolyl]pentyloxy,

6-[3-(2-nhexylphenyl)-5-1,2,4-oxadiazolyl]hexyloxy,

2-[3-(2,4-dimetilfenil)-5-1,2,4-oxadiazolyl]ethoxy and

1-[3-(2,3,5-trimetilfenil)-5-1,2,4-oxadiazolyl]ethoxy.

Examples isoxazolyl(lower)alkoxygroup, optionally substituted in isoxazoline ring by one or more lower alkyl groups include:

isoxazolecarboxylic, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in isoxazoline ring one or two described above unbranched and/or branched C1-6alkyl groups;

such as [(3-, 4 - or 5-)isoxazolyl]methoxy,

2-[(3-, 4 - or 5-)isoxazolyl]ethoxy,

1-[(3-, 4 - or 5-)isoxazolyl]ethoxy,

3-[(3-, 4 - or 5-)isoxazolyl]propoxy,

4-[(3-, 4 - or 5-)isoxazolyl]butoxy,

5-[(3-, 4 - or 5-)isoxazolyl]pentyloxy,

6-[(3-, 4 - or 5-)isoxazolyl]hexyloxy,

1,1-dimethyl-2[(3-, 4 - or 5-)isoxazolyl]ethoxy,

2-methyl-3-[(3-, 4 - or 5-)isoxazolyl]propoxy,

(3,5-dimethyl-4-isoxazolyl)methoxy,

[3-methyl-(4 - or 5-)isoxazolyl]methoxy,

[3-ethyl-(4 - or 5-)isoxazolyl]methoxy,

[4-npropyl-(3 - or 5-)isoxazolyl]methoxy,

[5-nbutyl-(3 - or 4-)isoxazolyl]methoxy,

[3-npentyl-(4 - or 5-)isoxazolyl]methoxy,

[4-nhexyl-(3 - or 5-)isoxazolyl]methoxy,

2-[3-methyl-(4 - or 5-)isoxazolyl]ethoxy,

1-[3-ethyl-(4 - or 5-)isoxazolyl]ethoxy,

3-[4-npropyl-(3 - or 5-)isoxazolyl]propoxy,

4-[5-nbutyl-(3 - or 4-)isoxazolyl]butoxy,

5-[3-npentyl-(4 - or 5-)isoxazolyl]pentyloxy and

6-[4-nhexyl-(3 - or 5-)isoxazolyl]hexyloxy.

Examples 1,3,4-oxadiazolyl(lower)alkoxygroup, optionally substituted in 1,3,4-oxadiazole ring of the phenyl group, and a phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups include:

1,3,4-oxadiazolyl, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in 1,3,4-oxadiazole ring one of the above described phenyl groups, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkyl groups;

such as [(2 - or 5-1,3,4-oxadiazolyl]methoxy,

2-[(2 - or 5-)1,3,4-oxadiazolyl]ethoxy,

1-[(2 - or 5-)1,3,4-oxadiazolyl]ethoxy,

3-[(2 - or 5-)1,3,4-oxadiazolyl]propoxy,

4-[(2 - or 5-)1,3,4-oxadiazolyl]butoxy,

5-[(2 - or 5-)1,3,4-oxadiazolyl]pentyloxy,

6-[(2 - or 5-)1,3,4-oxadiazolyl]hexyloxy,

1,1-dimethyl-2-[(2 - or 5-)1,3,4-oxadiazolyl]ethoxy,

2-methyl-3-[(2 - or 5-)1,3,4-oxadiazolyl]propoxy,

[2-(4-tert-butylphenyl)-5-1,3,4-oxadiazolyl]methoxy,

[2-(4-were)-5-1,3,4-oxadiazolyl]methoxy,

[5-(2-ethylphenyl)-2-1,3,4-oxadiazolyl]methoxy,

[2-(4-npropylphenyl)-5-1,3,4-oxadiazolyl]methoxy,

[5-(3-npentylphenol)-2-1,3,4-oxadiazolyl]methoxy,

[2-(2-nhexylphenyl)-5-1,3,4-oxadiazolyl]methoxy,

[2-(2,4-dimetilfenil)-5-1,3,4-oxadiazolyl]methoxy,

[2-(2,3,5-trimetilfenil)-5-1,3,4-oxadiazolyl]methoxy,

2-[2-(4-tert-butylphenyl)-5-1,3,4-oxadiazolyl]ethoxy,

1-[2-(3-were)-5-1,3,4-oxadiazolyl]ethoxy,

3-[5-(2-ethylphenyl)-2-1,3,4-oxadiazolyl]propoxy,

4-[2-(4-npropylphenyl)-5-1,3,4-oxadiazolyl]butoxy,

5-[5-(3-npentylphenol)-2-1,3,4-oxadiazolyl]pentyloxy,

6-[2-(2-nhexylphenyl)-5-1,3,4-oxadiazolyl]hexyloxy,

2-[2-(2,4-dimetilfenil)-5-1,3,4-oxadiazolyl]ethoxy and

1-[2-(2,3,5-trimetilfenil)-5-1,3,4-oxadiazolyl]ethoxy.

Examples of the lower alkanoyl(lower)alkoxygroup include alkanoyloxy where alcoholly fragment is nerazvit is certain or branched C 2-6alkanoyloxy group and the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as acetyloxy,

propionyloxy, 2-acetylators, 2-propionyloxy,

1 acetylators, 3 acetyldigoxin, 3 propionyloxy,

4 acetylators, 5-BUTYLPEROXY, 6-pentanedione,

1,1-dimethyl-2-hexanoate, 2-methyl-3-acetyldigoxin,

2 pentanoate, hexanoate.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more halogen atoms include phenyl group, optionally substituted in the phenyl ring by one to three halogen atoms, such as phenyl, 4-forfinal, 2.5-differenl, 2,4-differenl, 3,4-differenl, 3,5-differenl, 2,6-differenl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3-forfinal, 2-forfinal, 3-bromophenyl, 4-itfeel, 2-bromophenyl, 4-bromophenyl, 3,5-dichlorophenyl, 2,4,6-tryptophanyl, 3,4-differenl,

2-itfeel, 3-itfeel, 4-itfeel, 2,3-dibromophenyl,

2,4-diiodophenyl and 2,4,6-trichlorophenyl.

Examples thiazolyl(lower)alkoxygroup, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent n is necessarily substituted in the phenyl ring by one or more halogen atoms, include:

thiazolecarboxamide, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the thiazole ring with one or two members selected from the group consisting of the above-described non-branched and branched C1-6alkyl groups and phenyl groups, optionally substituted in the phenyl ring by one to three halogen atoms;

such as [(2-, 4 - or 5-)thiazolyl]methoxy,

2-[(2-, 4 - or 5-)thiazolyl]ethoxy,

1-[(2-, 4 - or 5-)thiazolyl]ethoxy,

3-[(2-, 4 - or 5-)thiazolyl]propoxy,

4-[(2-, 4 - or 5-)thiazolyl]butoxy,

5-[(2-, 4 - or 5-)thiazolyl]pentyloxy,

6-[(2-, 4 - or 5-)thiazolyl]hexyloxy,

1,1-dimethyl-2-[(2-, 4 - or 5-)thiazolyl]ethoxy,

2-methyl-3-[(2-, 4 - or 5-)thiazolyl]propoxy,

[2-phenyl-(4 - or 5-)thiazolyl]methoxy,

[2-(4-chlorophenyl)-4-methyl-5-thiazolyl]methoxy,

[2-(3-bromophenyl)-(4 - or 5-)thiazolyl]methoxy,

[2-(2-forfinal)-(4 - or 5-)thiazolyl]methoxy,

[2-(3,4-dichlorophenyl)-(4 - or 5-)thiazolyl]methoxy,

[2-(2,4,6-tryptophanyl)-(4 - or 5-)thiazolyl]methoxy,

[2-methyl-(4 - or 5-)thiazolyl]methoxy,

2-[2-ethyl-(4 - or 5-)thiazolyl]methoxy,

2-[4-phenyl-(2 or 5)thiazolyl]ethoxy,

3-[5-npropyl-(2 - or 4-)thiazolyl]propoxy,

4-[4-nbutyl-(2 - or 5-)thiazolyl]butoxy,

5-[2-npentyl-(4 - or 5-)thiazolyl]pentyloxy,

6-[5-nhexyl-(2 - or 4-)thiazoleacetate,

[2,4-dimethyl-5-thiazolyl]methoxy and

[2,4-diphenyl-5-thiazolyl]methoxy.

Examples benzoline groups, optionally substituted in the phenyl ring by one or more halogen atoms include benzoline group, optionally substituted in the phenyl ring by one to three halogen atoms, such as benzoyl, 4-perbenzoic, 2.5-differentail, 2,4-differentail, 3,4-differentail, 3,5-differentail, 2,6-differentail, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2.5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3-perbenzoic, 2-perbenzoic, 3-bromobenzoyl, 4-iodobenzyl, 2-bromobenzoyl, 4-bromobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-triterpenoid, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2,3-dibromobenzoic, 2,4-diiodobenzoic and 2,4,6-trichlorobenzoyl.

Examples of piperidinyloxy, optionally substituted in piperidinium the ring one or more benzoline groups, each bentely Deputy optionally substituted in the phenyl ring by one or more halogen atoms include:

piperidinyloxy, optionally substituted in piperidinium ring one to three above benzoline groups, each bentely Deputy optionally substituted in the phenyl ring by one to three halogen atoms;

such as (1-, 2-, 3 - or 4-)piperidinyloxy,

1-(4-shall Lorenzo)-(2-, 3 - or 4-piperidinyloxy,

1-(3-bromobenzoyl)-(2-, 3 - or 4-)piperidinyloxy,

1-benzoyl-(2-, 3 - or 4-)piperidinyloxy,

1-(2-perbenzoic)-(2-, 3 - or 4-)piperidinyloxy,

1-(2,4-dichlorobenzoyl)-(2-, 3 - or 4-)piperidinyloxy,

1-(2,4,6-triterpenoid)-(2-, 3 - or 4-)piperidinyloxy,

2-(3-chlorobenzoyl)-(1-, 3 - or 4-)piperidinyloxy,

3-(2-chlorbenzoyl)-(1-, 2 - or 4-)piperidinyloxy,

4-(2,3-dibromobenzyl)-(1-, 2 - or 3-)piperidinyloxy,

1,2-Dibenzoyl-(3 - or 4-)piperidinyloxy and

1,2,4-Dibenzoyl-3-piperidinyloxy.

Examples thienyl(lower)alkoxygroup include taylortatero, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as

[(2 - or 3-)thienyl]methoxy, 2-[(2 - or 3-)thienyl]ethoxy,

1-[(2 - or 3-)thienyl]ethoxy, 3-[(2 - or 3-)thienyl]propoxy,

4-[(2 - or 3-)thienyl]butoxy, 5-[(2 - or 3-)thienyl]pentyloxy,

6-[(2 - or 3-)thienyl]hexyloxy,

1,1-dimethyl-2-[(2 - or 3-)thienyl]ethoxy and

2-methyl-3-[(2 - or 3-)thienyl]propoxy.

Examples of phenylthio(lower)alkoxygroup include phenyltoloxamine, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as

penultimate, 2-penilties, 1 penilties,

3 phenylthiophene, 4-vinyltoluene, 5-phenylthiophene,

6 phenyltoloxamine, 1,1-dimethyl-2-penilties and/p>

2-methyl-3-phenylthiophene.

Examples carbamoylation lower alkoxygroup, optionally substituted by one or more lower alkyl groups include:

carbamoylation unbranched and branched C1-6alkoxygroup, optionally substituted in carbamoyl group one or two unbranched and/or branched C1-6alkyl groups;

such as carbamoylmethyl, 2-carbamoylethyl,

1 carbamoylphenoxy, 3 carbamoylphenoxy, 4-carbamoylphenoxy,

5-carbamoylphenoxy, 6-carbamoylphenoxy,

1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylphenoxy,

methylcarbamoylmethyl, 1 ethylcarbamate,

2-npropylgallate, 3 isopropylcarbodiimide,

4-nBUTYLCARBAMATE, 5-nintelcorporation,

6-nhexylcinnamaldehyde, dimethylcarbamoyl,

3 dimethylcyclopropane, 2-diisopropylcarbodiimide,

(Nethyl-N-n-propellerblades)methoxy and

2-(Nmethyl-N-n-exaltabitur)ethoxy.

Examples of the benzoyl(lower)alkoxygroup include benzoyloxy, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as benzoyloxy, 2-benzoylperoxy, 1 benzoylperoxy, 3 benzoylperoxy, 4-benzoylperoxy, 5-baie is serpentlike, 6 benzoylperoxy, 1,1-dimethyl-2-benzoylperoxy and 2-methyl-3-benzoylpropionic.

Examples pyridylcarbonyl(lower)alkoxygroup include pyridylcarbonyl, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as [(2-, 3 - or 4-)pyridylcarbonyl]methoxy,

2-[(2-, 3 - or 4-)pyridylcarbonyl]ethoxy,

1-[(2-, 3 - or 4-)pyridylcarbonyl]ethoxy,

3-[(2-, 3 - or 4-)pyridylcarbonyl]propoxy,

4-[(2-, 3 - or 4-)pyridylcarbonyl]butoxy,

5-[(2-, 3 - or 4-)pyridylcarbonyl]pentyloxy,

6-[(2-, 3 - or 4-)pyridylcarbonyl]hexyloxy,

1,1-dimethyl-2-[(2-, 3 - or 4-)pyridylcarbonyl]ethoxy and

2-methyl-3-[(2-, 3 - or 4-)pyridylcarbonyl]propoxy.

Examples imidazolyl(lower)alkoxygroup, optionally substituted in the imidazole ring by one or more phenyl(lower)alkyl groups include:

imidazolylalkyl, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the imidazole ring with one to three phenylalkylamine groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group;

such as [(1-, 2-, 4 - or 5-)imidazolyl]methoxy,

2-[(1-, 2-, 4 - or 5-)imidazolyl]ethoxy,

1-[(1-, 2-, 4 - or 5-)imidazolyl]ethoxy,

3-[(1-, 2-, 4 - or 5-)imidazolyl]prop is XI,

4-[(1-, 2-, 4 - or 5-)imidazolyl]butoxy,

5-[(1-, 2-, 4 - or 5-)imidazolyl]pentyloxy,

6-[(1-, 2-, 4 - or 5-)imidazolyl]hexyloxy,

1,1-dimethyl-2-[(1-, 2-, 4 - or 5-)imidazolyl]ethoxy,

2-methyl-3-[(1-, 2-, 4 - or 5-)imidazolyl]propoxy,

[1-benzyl-(2-, 4 - or 5-)imidazolyl]methoxy,

[1-(2-phenylethyl)-(2-, 4 - or 5-)imidazolyl]methoxy,

2-[2-(3-phenylpropyl)-(1-, 4 - or 5-)imidazolyl]ethoxy,

3-[4-(4-phenylbutyl)-(1-, 2 - or 5-)imidazolyl]propoxy,

5-[4-(5-fenilpentil)-(1-, 2 - or 4-)imidazolyl]pentyloxy,

6-[1-(6-phenylhexanoic)-(2-, 4 - or 5-)imidazolyl]hexyloxy,

[1,2-dibenzyl-(4 - or 5-)imidazolyl]methoxy and

[1,2,4-dibenzyl-5-imidazolyl]methoxy.

Examples of phenoxy(lower)alkoxygroup include phenoxyethoxy, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as phenoxyethoxy, 2-phenoxyethoxy, 1 phenoxyethoxy, 3 phenoxypropane, 4-phenoxyethoxy, 5-phenoxyphenoxy, 6-phenoxyacetate, 1,1-dimethyl-2-phenoxyethoxy and 2-methyl-3-phenoxypropane.

Examples of phenyl(lower)alkoxy-substituted lower alkoxygroup include fenilalaninammonii alkoxygroup, where each of the two alkoxy fragments represents an unbranched or branched C1-6alkoxygroup, such as phenylmethoxy, 2-(phenylmethoxy)ethoxy, 1-(phenylmethoxy)ethoxy, 3-(phenylmethoxy) propoxy, 4-(is animetake)butoxy, 5-(phenylmethoxy)pentyloxy, 6-(phenylmethoxy)hexyloxy, 1,1-dimethyl-2-(phenylmethoxy)ethoxy, 2-methyl-3-(phenylmethoxy)propoxy, 1-(2-phenylethane)ethoxy, 2-(1-phenylethane)ethoxy, 3-(3-phenylpropoxy)propoxy, 4-(4-phenylmethoxy)butoxy, 5-(5-phenylmethoxy)pentyloxy, 6-(6-phenylhexanoic)hexyloxy, (1,1-dimethyl-2-phenylethane)methoxy and 3-(2-methyl-3-phenylpropoxy)propoxy.

Examples isoindoline(lower)alkoxygroup, optionally substituted in isoindoline the ring one or more oxopropyl include:

isoindolines, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in isoindoline ring one or two exography;

such as [(1-, 2-, 4 - or 5-)isoindoline]methoxy,

2-[(1-, 2-, 4 - or 5-)isoindoline]ethoxy,

1-[(1-, 2-, 4 - or 5-)isoindoline]ethoxy,

3-[(1-, 2-, 4 - or 5-)isoindoline]propoxy,

4-[(1-, 2-, 4 - or 5-)isoindoline]butoxy,

5-[(1-, 2-, 4 - or 5-)isoindoline]pentyloxy,

6-[(1-, 2-, 4 - or 5-)isoindoline]hexyloxy,

1,1-dimethyl-2-[(1-, 2-, 4 - or 5-)isoindoline]ethoxy,

2-methyl-3-[(1-, 2-, 4 - or 5-)isoindoline]propoxy,

3-[1,3-dioxo-(2-, 4 - or 5-)isoindoline]propoxy,

[1-oxo-(2-, 3-, 4-, 5-, 6 - or 7-)isoindoline]methoxy,

2-[1,3-dioxo-(1-, 4 - or 5-)isoindoline]ethoxy,

4-[1-oxo-(2-, 3-, 4-, 5-, 6 - or 7-)isoindoline]butoxy,

5-[1,3-d is oxo-(1-, 4 - or 5-)isoindoline]pentyloxy and

6-[1-oxo-(2-, 3-, 4-, 5-, 6 - or 7-)isoindoline]hexyloxy.

Examples of the lower alkoxygroup, optionally substituted by one or more halogen atoms include unbranched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms, such as, in addition to the above, the lower alkoxygroup, triptoreline, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine and 5,6-dibromohexane.

Examples of the lower alkanoyl groups include unbranched and branched C1-6alcoholnye groups, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl,tert-butylcarbamoyl and hexanoyl.

Examples of amino groups, optionally substituted by one or more lower alkanolamine groups include amino groups, optionally substituted with one or two unbranched and/or branched C1-6alkanolamine groups, such as amino, formylamino, acetylamino, propionamido, bucillamine, isobutylamino, pentanediamine,tert-BUTYLCARBAMATE, hexanamine,N,N diatsetilamino andNacetyl-Npropionamido.

Examples of phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; phenyl groups; lower alkoxycarbonyl groups; fenoxaprop; lower alkylthio; lower alkylsulfonyl groups; phenyl(lower)alkoxygroup and amino groups, optionally substituted by one or more lower alkanolamine groups include:

mono - and diphenylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above halogen atoms; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms; phenyl groups; the above-described alkoxycarbonyl groups where the alkoxy fragment is nerasvetlena is or branched C 1-6alkoxygroup; fenoxaprop described above unbranched and branched C1-6alkylthio; above unbranched and branched C1-6alkylsulfonyl groups; the above fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, and the above-described amino groups, optionally substituted with one or two unbranched and/or branched C1-6alkanolamine groups;

such as benzyl, 1-phenethyl, 2-phenethyl, 3-phenylpropyl,

2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil,

6-phenylhexa, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl,

1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl,

1,2-diphenylether, 4-Chlorobenzyl, 2-Chlorobenzyl, 3-Chlorobenzyl,

3-tormentil, 4-tormentil, 2,3-dichlorobenzyl,

2,4,6-triptorelin, 3-trifloromethyl, 4-trifloromethyl,

2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-tert-butylbenzyl,

2,4-dimethylbenzyl, 2,4,6-trimethylbenzyl, 2-phenylbenzyl,

4-phenylbenzyl, 2,4-diphenylmethyl, 2,4,6-triphenylbenzene,

2-cryptomaterial, 3-cryptomaterial,

4-cryptomaterial, 2-methoxybenzyl, 3-methoxybenzyl,

4-methoxybenzyl, 3,4-dimethoxybenzyl, 3,4,5-trimethoxybenzyl,

4-methoxycarbonylbenzyl, 3-ethoxycarbonylphenyl,

2-npropoxy is carbonylmethyl, 2,4-dimethoxyaniline,

2,4,6-trimethoxybenzyl, 4-tert-butoxycarbonylmethyl,

3-phenoxybenzyl, 2-phenoxybenzyl, 4-phenoxybenzyl,

3,4-diphenoxybenzene, 3,4,5-Trypanosomosis, 4-methylthiophenyl,

3-methylthiophenyl, 2-methylthiophenyl, 2,4-dimethylthiophenol,

2,4,6-trimethylstyrene, 4-methylsulfonylbenzoyl,

3-methylsulfonylbenzoyl, 2-methylsulfonylbenzoyl,

3,4-dimethylsulphamoyl, 3,4,5-trimethylbenzyl,

4-benzyloxybenzyl, 3-benzyloxybenzyl, 2-benzyloxybenzyl,

2,4-dibenzalacetone, 2,4,6-tribenzylamine,

4-methoxy-3-Chlorobenzyl, 4-(Nacetylamino)benzyl, 3-aminobenzyl,

2-aminobenzyl, 4-aminobenzyl, 2,3-diaminobenzoic,

3,4,5-triaminobenzene and 4-methyl-3-terbisil.

Examples of the naphthyl(lower)alkyl groups include naphthylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(1 - or 2-)naphthyl]methyl 1-[(1 - or 2-)naphthyl]ethyl,

2-[(1 - or 2-)naphthyl]ethyl, 3-[(1 - or 2-)naphthyl]propyl,

2-[(1 - or 2-)naphthyl]propyl, 4-[(1 - or 2-)naphthyl]butyl,

5-[(1 - or 2-)naphthyl]pentyl, 4-[(1 - or 2-)naphthyl]pentyl,

6-[(1 - or 2-)naphthyl]hexyl, 2-methyl-3-[(1 - or 2-)naphthyl]propyl

and 1,1-dimethyl-2-[(1 - or 2-)naphthyl]ethyl.

Examples furyl(lower)alkyl group, optionally substituted in the furan ring with one or several is likemy lower alkoxycarbonyl groups, include:

fenilalanina group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the furan ring with one to three alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup;

such as [(2 - or 3-)furyl]methyl, 2-[(2 - or 3-)furyl]ethyl,

1-[(2 - or 3-)furyl]ethyl, 3-[(2 - or 3-)furyl]propyl,

4-[(2 - or 3-)furyl]butyl, 5-[(2 - or 3-)furyl]pentyl,

6-[(2 - or 3-)furyl]hexyl,

1,1-dimethyl-2-[(2 - or 3-)furyl]ethyl,

2-methyl-3-[(2 - or 3-)furyl]propyl,

[5-etoxycarbonyl-(2-, 3 - or 4-)furyl]methyl,

[5-methoxycarbonyl-(2-, 3 - or 4-)furyl]methyl,

[2-npropoxycarbonyl-(3-, 4 - or 5-)furyl]methyl,

[3-tert-butoxycarbonyl-(2-, 4 - or 5-)furyl]methyl,

[4-npentyloxybenzoyl-(2-, 3 - or 5-)furyl]methyl,

[2-nhexyloxybenzoyl-(3-, 4 - or 5-)furyl]methyl,

[2.5-dietoksikarbonil-(3 - or 4-)furyl]methyl and

[2,4,5-triethoxysilyl-3-furyl]methyl.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms include:

phenyl group, optionally substituted in the phenyl ring by one to three not OSVETLENIE and/or branched C 1-6alkyl groups, each alkyl substituent optionally substituted with one to three above described halogen atoms;

such as phenyl, 2-were, 3-were, 4-were,

2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl,

3-nbutylphenyl, 4-npentylphenol, 4-nhexylphenyl,

3,4-dimetilfenil, 3,4-diethylphenyl, 2,4-dimetilfenil,

2,5-dimetilfenil, 2,6-dimetilfenil, 3,4,5-trimetilfenil,

2-triptoreline, 3-triptoreline, 4-triptoreline,

3,5-deformational, 2,4,6-three(trifluoromethyl)phenyl and

2-methyl-4-triptoreline.

Examples thiazolyl(lower)alkyl group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted by one or more optionally halogen-substituted lower alkyl groups include tutorialnya group, where the alkyl fragment is an unbranched or branched C1-6alkyl group. These tutorialnya groups include those which are optionally substituted in the thiazole ring with one or two members selected from the above-described non-branched and branched C1-6alkyl groups and described is use phenyl groups, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkyl groups, each alkyl substituent optionally optionally substituted with one to three halogen atoms. More specific examples thiazolyl(lower)alkyl groups are

[(2-, 4 - or 5-)teasell]methyl, 2-[(2-, 4 - or 5-)thiazolyl]ethyl,

1-[(2-, 4 - or 5-)thiazolyl]ethyl,

3-[(2-, 4 - or 5-)thiazolyl]propyl,

4-[(2-, 4 - or 5-)thiazolyl]butyl,

5-[(2-, 4 - or 5-)thiazolyl]pentyl,

6-[(2-, 4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[(2-, 4 - or 5-)thiazolyl]ethyl,

[2-methyl-(4 - or 5-)thiazolyl]methyl,

[2-(4-triptoreline)-[(4 - or 5-)thiazolyl]methyl,

2-[4-ethyl-(2 - or 5-)thiazolyl]ethyl,

1-[5-(3-were)-(2 - or 4-)thiazolyl]ethyl,

3-[5-isopropyl-(2 - or 4-)thiazolyl]propyl,

4-[2-(2,4-dimetilfenil)-(4 - or 5-)thiazolyl]butyl,

5-[2-nbutyl-(4 - or 5-)thiazolyl]pentyl,

6-[4-(2,4,6-trimetilfenil)-(2 - or 5-)thiazolyl]hexyl,

(2,4-dimethyl-5-thiazolyl)methyl,

[2-(4-triptoreline)-4-phenyl-5-thiazolyl]methyl and

(2-phenyl-4-thiazolyl)methyl.

Examples tetrazolyl(lower)alkyl group, optionally substituted in tetrazolium ring by one or more lower alkyl groups include:

tetraallylsilane group, where the alkyl fragment is an unbranched or branched C1-6alkylen the th group, optionally substituted in tetrazolium the ring one or more unbranched and/or branched C1-6alkyl groups,

such as [(1-or 5-)tetrazolyl]methyl,

2-[(1 - or 5-) tetrazolyl]ethyl, 1-[(1 - or 5-)tetrazolyl]ethyl,

3-[(1 - or 5-)tetrazolyl]propyl, 4-[(1 - or 5-)tetrazolyl]butyl,

5-[(1 - or 5-)tetrazolyl]pentyl, 6-[(1 - or 5-)tetrazolyl]butyl,

5-(1-methyl-5-tetrazolyl)pentyl, 6-(1-methyl-5-tetrazolyl)hexyl,

(5-methyl-1-tetrazolyl)methyl, 2-(5-ethyl-1-tetrazolyl)hexyl,

1,1-dimethyl-2-[(1 - or 5-)tetrazolyl]ethyl,

2-methyl-3-[(1 - or 5-)tetrazolyl]propyl,

(1-methyl-5-tetrazolyl)methyl, (1-ethyl-5-tetrazolyl)methyl,

2-(1-npropyl-5-tetrazolyl)ethyl, 1-(1-nbutyl-5-tetrazolyl)ethyl,

3-(1-npentyl-5-tetrazolyl)propyl,

4-(1-nhexyl-4-tetrazolyl)butyl,

3-(5-isopropyl-1-tetrazolyl)propyl,

4-(5-second-butyl-1-tetrazolyl)butyl,

5-(5-isopentyl-1-tetrazolyl)pencil and

6-(5-nhexyl-1-tetrazolyl)hexyl.

Examples benzothiazyl(lower)alkyl group, optionally substituted in benzothiophene ring by one or more halogen atoms include:

sensationally group, where the alkyl fragment is an unbranched and branched C1-6alkyl group, optionally substituted in benzothiophene ring with one to three halogen atoms;

the such as [(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]methyl,

2-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]ethyl,

1-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]ethyl,

3-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]propyl,

4-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]butyl,

5-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]pentyl,

6-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]hexyl,

1,1-dimethyl-2-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]ethyl,

2-methyl-3-[(2-, 3-, 4-, 5-, 6 - or 7-)benzothieno]propyl,

[5-chloro-(2-, 3-, 4-, 6 - or 7-)benzothieno]methyl,

[4-bromo-(2-, 3-, 5-, 6 - or 7-)benzothieno]methyl,

[6-fluoro-(2-, 3-, 4-, 5 -, or 7-)benzothieno]methyl,

[7-iodine-(2-, 3-, 4-, 5 -, or 6-)benzothieno]methyl,

[2-chloro-(3-, 4-, 5-, 6 - or 7-)benzothieno]methyl,

[4,5-dichloro-(2-, 3-, 6 - or 7-)benzothieno]methyl,

[2,4,5-chloro-(3-, 6 - or 7-)benzothieno]methyl,

2-[6-fluoro-(2-, 3-, 4-, 5 -, or 7-)benzothieno]ethyl,

1-[7-iodine-(2-, 3-, 4-, 5 -, or 6-)benzothieno]ethyl,

3-[2-chloro-(3-, 4-, 5-, 6 - or 7-)benzothieno]propyl,

4-[4,5-dichloro-(2-, 3-, 6 - or 7-)benzothieno]butyl,

5-[2,4,5-trichloro-(3-, 6 - or 7-)benzothieno]pentyl and

6-[5-chloro-(2-, 3-, 4-, 6 - or 7-)benzothieno]hexyl.

Examples of the lower etkinlik groups include unbranched and branched C2-6alkyline groups such as ethynyl, 2-PROPYNYL, 2-butynyl, 3-butynyl, 1-methyl-2-PROPYNYL, 2-pentenyl and 2-hexenyl.

Examples of the lower alkenyl groups include unbranched and branched C2-6alkeneamine group containing one to three double bonds, is such as vinyl, 1-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-propenyl, 2-butenyl, 1-butenyl, 3-butenyl, 2-pentenyl, 1-pentenyl, 3-pentenyl, 4-pentenyl, 1,3-butadienyl, 1,3-pentadienyl, 2-penten-4-yl, 2-hexenyl, 1-hexenyl, 5-hexenyl, 3-hexenyl, 4-hexenyl, 3,3-dimethyl-1-propenyl, 2-ethyl-1-propenyl, 1,3,5-hexatriene, 1,3-hexadiene and 1,4-hexadienyl.

Examples benzoimidazolyl(lower)alkyl groups include benzoimidazolyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as

[(1-, 2-, 4 - or 5-)benzoimidazolyl]methyl,

2-[(1-, 2-, 4 - or 5-)benzoimidazolyl]ethyl,

1-[(1-, 2-, 4 - or 5-)benzoimidazolyl]ethyl,

3-[(1-, 2-, 4 - or 5-)benzoimidazolyl]propyl,

4-[(1-, 2-, 4 - or 5-)benzoimidazolyl]butyl,

5-[(1-, 2-, 4 - or 5-)benzoimidazolyl]pentyl,

6-[(1-, 2-, 4 - or 5-)benzoimidazolyl]hexyl,

1,1-dimethyl-2-[(1-, 2-, 4 - or 5-)benzoimidazolyl]ethyl and

2-methyl-3-[(1-, 2-, 4 - or 5-)benzoimidazolyl]propyl.

Examples of pyridyl(lower)alkyl groups include pyridinoline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(2-, 3 - or 4-)pyridyl]methyl, 2-[(2-, 3 - or 4-)pyridyl]ethyl, 1-[(2-, 3 - or 4-)pyridyl]ethyl, 3-[(2-, 3 - or 4-)pyridyl]propyl, 4-[(2-, 3 - or 4-)pyridyl]butyl, 1,1-dimethyl-2-[(2-, 3- or 4-)pyridyl]ethyl, 5-[(2-, 3 - or 4-) pyridyl]pentyl, 6-[(2-,3 - or 4-)pyridyl]hexyl, 1-[(2-, 3 - or 4-)pyridyl]isopropyl and 2-methyl-3-[(2-, 3 - or 4-)pyridyl]propyl.

Examples imidazolyl(lower)alkyl group, optionally substituted in the imidazole ring by one or more phenyl(lower)alkyl groups include:

imidazolylalkyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the imidazole ring with one to three above phenylalkylamine groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group;

such as [(1-, 2-, 4 - or 5-)imidazolyl]methyl,

2-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

1-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

3-[(1-, 2-, 4 - or 5-)imidazolyl]propyl,

4-[(1-, 2-, 4 - or 5-)imidazolyl]butyl,

1,1-dimethyl-2-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

5-[(1-, 2-, 4 - or 5-)imidazolyl]pentyl,

6-[(1-, 2-, 4 - or 5-)imidazolyl]hexyl,

1-[(1-, 2-, 4 - or 5-)imidazolyl]isopropyl,

2-methyl-3-[(1-, 2-, 4 - or 5-)imidazolyl]propyl,

[1-benzyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(2-phenylethyl)-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(1-phenylethyl)-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(3-phenylpropyl)-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(4-phenylbutyl)-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(5-fenilpentil)-(2-, 4 - or 5-)imidazolyl]methyl,

[1-(6-phenylhexa)-(2-, 4 - or 5-)imidazolyl]methyl,

2-[2-benzo is l-(1-, 4 - or 5-)imidazolyl]ethyl,

1-[4-(4-phenylethyl)-(1 - or 2-)imidazolyl]ethyl,

3-[2-(2-phenylethyl)-(1-, 4 - or 5-)imidazolyl]methyl,

4-[1-(3-phenylpropyl)-(2-, 4 - or 5-)imidazolyl]butyl,

5-[1-(4-phenylbutyl)-(2-, 4 - or 5-)imidazolyl]pentyl,

6-[1-(5-fenilpentil)-(2-, 4 - or 5-)imidazolyl]hexyl,

[1,2-dibenzyl-(4 - or 5-)imidazolyl]methyl and

(1,2,4-dibenzyl-5-imidazolyl)methyl.

Examples of the lower alkylsulfonyl groups, optionally substituted by one or more halogen atoms include unbranched and branched C1-6alkylsulfonyl group, optionally substituted with one to three halogen atoms, such as, in addition to the above-described lower alkylsulfonyl groups, trifloromethyl, trichloromethylsulfuryl, chloromethanesulfonyl, brommersvlei, pharmacysulfacet, madmetalslayer, diplomatischer, dibromodulcitol, 2-Kharatishvili, 2,2,2-cryptonemiales, 2,2,2-trichlorethylene, 3-chloropropanesulfonyl, 2,3-dichloropropionitrile, 4,4,4-trichlorobutylene,

4-terbutaline, 5-khlorfenilalanin,

3-chloro-2-methylpropylsulfonic, 5-Bromhexine and

5,6-dibromohexane.

Examples alkoxycarbonyl groups, optionally substituted by one or more halogen atoms include:

alkoxycarbonyl group, where the alkoxy fragment pre whom represents an unbranched or branched C 1-10alkoxygroup, optionally substituted with one to three halogen atoms;

such as, in addition to the above-described lower alkoxycarbonyl groups,nheptyloxybiphenyl,

noctyloxybiphenyl,nnonlexically,ndecyloxybenzoic,

2-ethylhexyloxymethyl, trevormarsicano,

trichloromethylcarbnol, chlorocarbons,

bromocarbons, formicoxenini, iodocholesterol,

deformational, dibromocarbene,

2-chlorocarbons, 2-forecasterror,

2,2,2-cryptgetuserkey, 2,2,2-trichlorocyanuric,

3-chloropropionyl, 2,3-dichloropropionic,

4,4,4-trichloroethanol, 4-permutational,

4-chlorocarbons, 5-chlortetracycline,

3-chloro-2-methylpropanesulphonic, 5-bromohexadecane,

5,6-dibromosuccinic, 7,7,6-trichlorophenoxypropionic,

8-bromodeoxyuridine, 9,9,9-crypteroniaceae and

10,10,10-trichloromethylcarbnol.

Examples pyridylcarbonyl groups, optionally substituted in the pyridine ring by one or more members selected from the group consisting of pyrrolidine groups and halogen atoms include:

pyridylcarbonyl group, optionally substituted in the pyridine ring with one to three members selected by isgroup, consisting of pyrrolidine groups and halogen atoms;

such as (2-, 3 - or 4-)pyridylcarbonyl,

2-chloro-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,6-dichloro-(3-, 4 - or 5-)pyridylcarbonyl,

2-(1-pyrrolyl)-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2-bromo-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,6-debtor-(3-, 4 - or 5-)pyridylcarbonyl,

4-(1-pyrrolyl)-(2 - or 3-)pyridylcarbonyl,

3-chloro-(2-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,5-dibromo-(3-, 4 -, or 6-)pyridylcarbonyl,

2-(1-pyrrolyl)-4-chloro-(3-, 5 -, or 6-)pyridylcarbonyl,

2,4,6-Cryptor-(3 - or 5-)pyridylcarbonyl and

2,4-di(1-pyrrolyl)-(3-, 5 -, or 6-)pyridylcarbonyl.

Examples peredelnyh groups, optionally substituted in the pyridine ring by one or more members selected from the group consisting of lower alkyl groups and lower alkoxygroup include:

peredelnye group, optionally substituted in the pyridine ring with one to three members selected from the group consisting of the above-described non-branched and branched C1-6the alkyl groups described above unbranched and branched C1-6alkoxygroup;

such as (2-, 3 - or 4-)pyridyl,

2-methyl-(3-, 4-, 5 -, or 6-)pyridyl,

3-methyl-(2-, 4-, 5 -, or 6-)pyridyl,

2-methoxy-(3-, 4-, 5 -, or 6-)pyridyl,

4-ethyl-(2 - or 3-)pyridyl,

3-npropyl-(2-, 4-, 5 -, or 6-)pyridyl,

2-tert-butyl-(3-, 4-, 5 -, or 6-)pyridyl,

2-npentyl-(3-, 4-, 5 -, or -)pyridyl,

3-nhexyl-(2-, 4-, 5 -, or 6-)pyridyl,

2,4-dimethyl-(3-, 5 -, or 6-)pyridyl,

2,4,6-trimethyl-(3 - or 5-)pyridyl,

3 ethoxy-(2-, 4-, 5 -, or 6-)pyridyl,

2 isopropoxy-(3-, 4-, 5 -, or 6-)pyridyl,

2-nbutoxy-(3-, 4-, 5 -, or 6-)pyridyl,

4-npentyloxy-(2 - or 3-)pyridyl,

2-nhexyloxy-(3-, 4-, 5 -, or 6-)pyridyl,

2,3-dimethoxy-(4-, 5 -, or 6-)pyridyl,

3-methyl-(2-, 4-, 5 -, or 6-)pyridyl,

3,4,5-trimetoksi-(2 - or 6-)pyridyl and

2-methyl-3-methoxy-(4-, 5 -, or 6-)pyridyl.

Examples of amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups include amino groups, optionally substituted by one or two members selected from the group consisting of unbranched and branched C1-6alkyl groups and unbranched and branched C1-6alkanoyl groups,

such as amino, methylamino, ethylamino,npropylamino,

isopropylamino,nbutylamino,tert-butylamino,npentylamine,

nhexylamino, dimethylamino, diethylamino, di-npropylamino,

di-nbutylamino, di-npentylamine, di-nhexylamino,

Nmethyl-Nethylamino,Nethyl-N-n-propylamino,

Nmethyl-N-n-butylamino,Nmethyl-N-n-hexylamino, formylamino,

acetylamino, propicillin is, bucillamine, isobutylamino,

pentanediamine,tert-BUTYLCARBAMATE, hexanamine,

N,N-diatsetilamino,Nacetyl-Npropionamido,

Nmethyl-Nacetylamino andNethyl-Npropionamido.

Examples pyrrolidinyl groups, optionally substituted in the pyrolidine ring one or more oxopropyl include pyrrolidinyl group, optionally substituted by one or two exography, such as (1-, 2 - or 3-)pyrrolidinyl, 2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinyl and 2.5-dioxo-(1 - or 3-)pyrrolidinyl.

Examples piperidinyl groups, optionally substituted in piperidinium ring by one or more lower alkyl groups include piperidinyl group, optionally substituted in piperidinium ring one to three unbranched and/or branched C1-6alkyl groups, such as

(1-, 2-, 3 - or 4-)piperidinyl,

1-methyl-(2-, 3 - or 4-)piperidinyl,

1-ethyl-(2-, 3 - or 4-)piperidinyl,

1-npropyl-(2-, 3 - or 4-)piperidinyl,

1-isopropyl-(2-, 3 - or 4-)piperidinyl,

1-nbutyl-(2-, 3 - or 4-)piperidinyl,

1-npentyl-(2-, 3 - or 4-)piperidinyl,

1-nhexyl-(2-, 3 - or 4-)piperidinyl,

1,2-dimethyl-(3-, 4-, 5 -, or 6-)piperidinyl,

1,2,3-trimethyl-(4-, 5 -, or 6-)piperidinyl,

2-npropyl-(1-, 3-, 4-, 5 -, or 6-)piperidinyl,

3-ethyl-(1-, 2-, 4-, 5 -, or 6-)is piperidinyl and

2-methyl-4-isopropyl-(1-, 3-, 5 -, or 6-)piperidinyl.

Examples carbamoyl groups, optionally substituted by one or more lower alkyl groups include carbamoyl group, optionally substituted with one or two unbranched and/or branched C1-6alkyl groups, such as carbarnoyl, methylcarbamoyl, ethylcarbitol,

npropellerblades, isopropylcarbamate,nbutylcarbamoyl,

tert-butylcarbamoyl,nintercalator,nexaltabitur,

dimethylcarbamoyl, diethylcarbamoyl, di-npropyl carbarnoyl,

di-nbutylcarbamoyl, di-nintercalator, di-nexaltabitur,

Nmethyl-Nethylcarbitol,Nethyl-N-n-propellerblades,

Nmethyl-N-n-butylcarbamoyl andNmethyl-N-n-exaltabitur.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; fenoxaprop; lower alkoxygroup, optionally substituted by one or more halogen atoms; lower alkylthio; lower alkylsulfonyl groups; amino groups, optionally substituted by one or more members selected from the group comprised the soup from lower alkyl groups and lower alkanoyl groups; pyrrolidinyl groups, optionally substituted in the pyrolidine ring one or more exography; piperidinyl groups, optionally substituted in piperidinium ring by one or more lower alkyl groups; lower alkenyl groups; aminosulfonyl group; a hydroxy-group; carbamoyl groups, optionally substituted by one or more lower alkyl groups; phenyl(lower)alkoxygroup and ceanography include:

phenyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above halogen atoms; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; fenoxaprop; above unbranched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkylthio; above unbranched and branched C1-6alkylsulfonyl groups; the above-described amino groups, optionally substituted by one or two members selected from the group consisting of unbranched and branched C1-6alkyl groups and unbranched and branched C1-6alkanoyl groups; above pyrrolidine is lnyh groups, optionally substituted in the pyrolidine ring one or two exography; above piperidinyl groups, optionally substituted in piperidinium ring one to three unbranched and/or branched C1-6alkyl groups; the above-described non-branched and branched C2-6alkenyl groups containing one to three double bonds; aminosulfonyl group; a hydroxy-group; the above carbamoyl groups, optionally substituted with one or two unbranched and/or branched C1-6alkyl group; the above fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, and cyanopropyl;

such as phenyl, 4-phenoxyphenyl, 3-phenoxyphenyl, 2-phenoxyphenyl,

4-isopropylphenyl, 3-isopropylphenyl, 2-isopropylphenyl,

4-tert-butylphenyl, 4-were, 3-were, 2nd were,

2,3-dimetilfenil, 2,4-dimetilfenil, 3, 5dimethylphenyl,

2,4,6-trimetilfenil, 4-methyl-3-methoxyphenyl,

4-triptoreline, 3-triptoreline, 2-triptoreline,

4-methyl-3-chlorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl,

2-forfinal, 3-forfinal, 4-forfinal, 3-bromophenyl,

3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,4,5-trichlorophenyl,

2,4,6-tryptophanyl, 3,5-differenl, 3-chloro-4-forfinal,

2-chloro-5-forfinal, 3-fluoro-methoxyphenyl,

3-chloro-4-methoxyphenyl, 3-chloro-4-hydroxyphenyl, 4-methoxyphenyl,

3-methoxyphenyl, 2-methoxyphenyl, 2,4-acid,

3,4-acid, 2,4,6-trimethoxyphenyl,

2-methoxy-5-chlorophenyl, 2-methoxy-5-acetylaminophenol,

2-chloro-5-acetylaminophenol, 4-ethoxyphenyl, 4-trifloromethyl,

3-trifloromethyl, 2-trifloromethyl,

3-methoxy-5-triptoreline, 4-methylthiophenyl, 3-methylthiophenyl,

2-methylthiophenyl, 2-(1-methyl-1-vinyl)phenyl, 4-vinylphenol,

3-dimethylaminophenyl, 4-methylaminophenol,

2-(Nmethyl-Nacetylamino)phenyl, 3-acetylaminophenol,

4-propionylcarnitine, 4-acetylaminophenol, 2-acetylaminophenol,

4-aminosulphonylphenyl, 3-aminosulphonylphenyl,

2-aminosulphonylphenyl, 4-methylthiophenyl, 3-methylthiophenyl,

2-methylthiophenyl, 4-methylsulfinylphenyl, 3-methylsulfinylphenyl,

2-methylsulfinylphenyl, 4-methylcarbamoylmethyl, 3-carbamoylmethyl,

2-ethylcarbamate, 2-benzyloxyphenyl, 3-benzyloxyphenyl,

4-benzyloxyphenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl,

2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl,

4-[2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinyl]phenyl,

3-[2,5-dioxo-(1 - or 3-)pyrrolidinyl]phenyl,

4-[4-methyl-(1-, 2 - or 3-)piperazinil]phenyl,

3-[4-ethyl-(1-, 2 - or 3-)piperazinil]phenyl and

2-[4-isopropyl-(1-, 2 - or 3-)piperazinil]phenyl.

Examples cycloalkyl groups, optional C is displaced in cycloalkene ring by one or more lower alkyl groups, include C3-8cycloalkyl group, optionally substituted in cycloalkene ring one to three unbranched and/or branched C1-6alkyl groups, such as, in addition to the above cycloalkyl groups,

1-methylcyclopropyl, 1-methylcyclopentene, 1-methylcyclohexyl,

2-methylcyclohexyl, 1-methylcyclobutene, 1-ethylcyclohexyl,

1-npropylcyclohexyl, 1,2-dimethylcyclohexyl,

1,4,5-trimethylcyclohexyl, 1-nbutylcyclohexyl,

1-npentylcyclohexyl and 1-nsexycollegegirl.

Examples of amino groups, optionally substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups include:

amino group, optionally substituted by one or two members selected from the group consisting of phenyl groups and unbranched and branched C1-6alkyl groups;

such as amino, methylamino, ethylamino,npropylamino, isopropylamino,nbutylamino,tert-butylamino,npentylamine,nhexylamino, dimethylamino, diethylamino, di-npropylamino, di-nbutylamino, di-npentylamine, di-nhexylamino,Nmethyl-Nethylamino,Nethyl-N-n-propylamino,Nmethyl-N-n-butylamino,Nmethyl-N-n-hexylamino, phenylamino,N,N-diphenylamine is, Nmethyl-Nphenylamino,Nethyl-Nphenylamino andN-n-propyl-Nphenylamino.

Examples benzoline groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; fenoxaprop; phenyl group; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; lower alkanoyl groups; nitro; ceanography; amino groups, optionally substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups; pyrrolidinyl groups, optionally substituted in the pyrolidine ring one or more exography; pyrrolidine groups; pyrazolidine group; 1,2,4-triazolyl groups and imidazolinium groups, include:

benzoline group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms; fenoxaprop; phenyl groups; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkoxygroup; above unbranched and branched C1-6alkanoyl groups; nitro; ceanography; the above amine the groups, optionally substituted by one or two members selected from the group consisting of phenyl groups and unbranched and branched C1-6the alkyl groups described above pyrrolidinyl groups, optionally substituted in the pyrolidine ring one or two exography; pyrrolidine groups; pyrazolidine group; 1,2,4-triazolyl groups and imidazolinium groups;

such as benzoyl, 4-methoxybenzoyl, 3-methoxybenzoyl,

2-methoxybenzoyl, 2,4-dimethoxybenzoyl, 3,4,5-trimethoxybenzoyl,

2-methoxy-5-chlorobenzoyl, 4-phenoxybenzoic, 2-phenoxybenzoic,

3-phenoxybenzyl, 4-chlorobenzoyl, 3-chlorobenzoyl, 2-chlorobenzoyl,

2,6-dichlorobenzoyl, 2-chloro-4-perbenzoic, 2,4,6-triterpenoid,

4-bromobenzoyl, 3-perbenzoic, 4-trifloromethyl,

3-trifloromethyl, 2-trifloromethyl,

3-fluoro-2-methylbenzoyl, 4-methylbenzoyl, 3-methylbenzoyl,

2-methylbenzyl, 3,4-dimethylbenzoyl, 2,4,5-trimethylbenzoic,

2-phenylbenzyl, 3-vinylbenzyl, 4-vinylbenzyl, 4-nitrobenzoyl,

3-nitrobenzoyl, 2-nitrobenzoyl, 2-dimethylaminobenzoyl,

3-methylaminophenol, 4-(Nmethylaniline)benzoyl,

2-anilinomethyl, 3-cyanobenzoyl, 4-cyanobenzoyl,

2-cyanobenzoyl, 4-acetylbenzoic, 2-propenylbenzene,

3-butylbenzoyl, 4-[(1-, 2 - or 3-)pyrrolyl]benzoyl,

4-[(1-, 3-, 4 - or 5-)pyrazolyl]benzoyl,

4-[(1-, 3 - or 5-)1,2,4-triazole is l]benzoyl,

4-[(1-, 2-, 4 - or 5-)imidazolyl]benzoyl and

4-[2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinyl]benzoyl.

Examples of the lower alkylenedioxy include unbranched and branched C1-4alkylene groups, such as methylenedioxy, Ethylenedioxy, trimethylenediamine, tetramethoxy.

Examples benzoline groups, substituted in the phenyl ring by one or more lower alkylenedioxy include

benzoline group substituted in the phenyl ring by one or more of the above non-branched and branched C1-4alkylenedioxy, such as 3,4-methylenedioxybenzyl, 2,3-atlantooccipital, 3,4-trimethylhexanoyl and 2,3-tetramethyldisilane.

Examples cycloalkylcarbonyl groups include cycloalkylcarbonyl group, where cycloalkyl fragment is a C3-8cycloalkyl group, such as cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexylcarbonyl, cyclohexylcarbonyl and cyclooctylamine.

Examples fuelleborni groups include 2 - or 3-)fullcarbon.

Examples afterburning groups include (1 or 2)afterburner.

Examples phenoxycarbonyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, lower al the ilen groups, atoms, halogen and nitro, include:

phenoxycarbonyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above-described non-branched and branched C1-6alkoxygroup described above unbranched and branched C1-6alkyl groups, halogen atoms and nitro;

such as phenoxycarbonyl, 4-chlorophenoxyacetic,

3-chlorphenoxamine, 2-chlorphenoxamine,

3,4-dichlorophenoxyacetic, 2,4,6-trichlorophenoxyacetic,

4-pertenecieron, 3-pertenecieron,

2-pertenecieron, 2,4-divergenceerror,

3,4,5-cryptorhynchinae, 4-bromophenanthrene,

2-chloro-4-methoxyphenethyl, 3-fluoro-5-methylphenoxyacetic,

4-methoxyphenethyl, 3-methoxyprogesterone,

2-methoxyprogesterone, 3,4-dimethoxyphenethylamine,

2,4,5-trimethoxyphenethylamine, 4-methylphenoxyacetic,

3-methylphenoxyacetic, 2-methylphenoxyacetic,

2.5-dimethylphenylcarbinol, 2,3,4-trimethylhexanoyl,

4-nitrophenoxyacetic, 3-nitrophenoxyacetic,

2-nitrophenoxide, 2,4-dinitroresorcinol and

2,4,6-trinitroresorcinol.

Examples of phenyl(lower)alkoxycarbonyl groups, optionally substituted in the phenyl ring by one or more States, using the data from the group consisting of halogen atoms and nitro, include:

generalquartiermeister group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms and nitro;

such as benzyloxycarbonyl, 2-fenilalaninammonii,

1-fenilalaninammonii, 3-phenylpropionyl,

4-privateserver, 5-phenylmethylsulphonyl,

6-vanillacracker, 1,1-dimethyl-2-fenilalaninammonii,

2-methyl-3-phenylpropionyl, 4-chlorobenzenesulfonyl,

3-chlorobenzylidene, 2-chlorobenzenesulfonyl,

3,4-dichlorobenzenesulfonyl, 2,4,6-trichlorophenoxypropionic,

4-forantimicrobial, 3-forantimicrobial,

2-forantimicrobial, 2,4-differentlocations,

3,4,5-triftoratsetilatsetonom, 4-bromobenzyloxycarbonyl,

4-nitrobenzenesulfonyl, 3-nitrobenzanthrone,

2-nitrobenzenesulfonyl, 2,4-dinitrobenzenesulfonyl,

2,4,6-trinitrobenzenesulfonic and

2-nitro-4-chlorobenzenesulfonyl.

Examples piperidinyl groups, optionally substituted in piperidinium ring by one or more members selected from the group consisting of lower alkyl groups; lower alkanoyl the groups; benzoline groups, optionally substituted in the phenyl ring by one or more halogen atoms, and phenyl groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

piperidinyl group, optionally substituted in piperidinium ring one to three members selected from the group consisting of the above-described non-branched and branched C1-6the alkyl groups described above unbranched and branched C1-6alkanoyl groups; the above-described benzoline groups, optionally substituted in the phenyl ring by one to three halogen atoms, and the above-described phenyl groups, optionally substituted in the phenyl ring by one to three halogen atoms;

such as (1-, 2-, 3 - or 4-)piperidinyl,

1-methyl-(2-, 3 - or 4-)piperidinyl,

1-acetyl-(2-, 3 - or 4-)piperidinyl,

1-benzoyl-(2-, 3 - or 4-)piperidinyl,

1-(4-chlorbenzoyl)-(2-, 3 - or 4-)piperidinyl,

1-(3-bromobenzoyl)-(2-, 3 - or 4-)piperidinyl,

1-benzoyl-(2-, 3 - or 4-)piperidinyl,

1-(4-perbenzoic)-(2-, 3 - or 4-)piperidinyl,

1-(2,4-dichlorobenzoyl)-(2-, 3 - or 4-)piperidinyl,

1-(2,4,6-triterpenoid)-(2-, 3 - or 4-)piperidinyl,

2-(3-chlorobenzoyl)-(1-, 3 - or 4-)piperidinyl,

3-(2-chlorbenzoyl)-(1-, 2 - or 4-)piperidinyl,

4-(2,3-dibromobenzyl)-(1-, 2 - or 3-)piperidinyl,

1,2-Dibenzoyl-(3 - or 4-)piperidinyl,

1,2,4-Dibenzoyl-3-piperidinyl,

1,4-dimethyl-(2-, 3-, 5 -, or 6-)piperidinyl,

1,2,4-trimethyl-(3-, 5 -, or 6-)piperidinyl,

1-benzoyl-2-methyl-(3-, 4-, 5 -, or 6-)piperidinyl,

1-phenyl-2-methyl-(3-, 4-, 5 -, or 6-)piperidinyl,

1-acetyl-3-methyl-(2-, 4-, 5 -, or 6-)piperidinyl,

1-phenyl-(2-, 3 - or 4-)piperidinyl,

1-(4-chlorophenyl)-(2-, 3 - or 4-)piperidinyl,

1-(3-bromophenyl)-(2-, 3 - or 4-)piperidinyl,

1-(4-itfeel)-(2-, 3 - or 4-)piperidinyl,

1-(4-forfinal)-(2-, 3 - or 4-)piperidinyl,

1-(2,4-dichlorophenyl)-(2-, 3 - or 4-)piperidinyl,

1-(2,4,6-tryptophanyl)-(2-, 3 - or 4-)piperidinyl,

2-(3-chlorophenyl)-(1-, 3-, 4-, 5 -, or 6-)piperidinyl,

3-(2-chlorophenyl)-(1-, 2-, 4-, 5 -, or 6-)piperidinyl,

4-(2,3-dibromophenyl)-(1-, 2 - or 3-)piperidinyl,

1,2-diphenyl-(3-,4-, 5 -, or 6-)piperidinyl and

1,2,4-triphenyl-(3-, 5 -, or 6-)piperidinyl.

Examples tetrahydropyranyl(lower)alkyl groups include tetrahydropyranyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as

[(2-, 3 - or 4-)tetrahydropyranyl]methyl,

2-[(2-, 3 - or 4-)tetrahydropyranyl]ethyl,

1-[(2-, 3 - or 4-)tetrahydropyranyl]ethyl,

3-[(2-, 3 - or 4-)tetrahydropyranyl]propyl,

4-[(2-, 3 - or 4-)tetrahydropyranyl]butyl,

1,1-dimethyl-2-[(2-, 3 - or 4-)tetrahydropyranyl]ethyl,

5-[(2-, 3 - or 4-)tetrahydropyranyl]pentyl,

6-[(2-, 3 - or 4-)tetrahydropyranyl]hexyl,

1-[(2-, 3 - or 4-)tetrahydropyranyl]from the propyl and

2-methyl-3-[(2-, 3 - or 4-)tetrahydropyranyl]propyl.

Examples of phenyl(lower)alkyl group, optionally substituted in the alkyl group by one or more lower alkoxycarbonyl groups and optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups, optionally substituted by one or more halogen atoms, lower alkoxygroup, optionally substituted by one or more halogen atoms, and hydroxy-group, include:

mono - and diphenylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the alkyl group by one or more lower alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, and optionally substituted in the phenyl group by one to three members selected from the group consisting of halogen atoms described above unbranched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms described above unbranched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms, and hydroxy-group;

such as ensil, 1-phenethyl, 2-phenethyl, 3-phenylpropyl,

2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil,

6-phenylhexa, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl, 1,1-dimethyl-1-phenylmethyl, 1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl, 1,2-diphenylether, 4-Chlorobenzyl, 2-Chlorobenzyl, 3-Chlorobenzyl, 3-tormentil, 4-tormentil, 3-bromobenzyl, 2,3-dichlorobenzyl, 2,6-dichlorobenzyl, 2,4,6-triptorelin, 2-(4-chlorophenyl)ethyl, 2-(2-forfinal)ethyl, 2-(3-forfinal)ethyl, 3-trifloromethyl, 4-trifloromethyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-tert-butylbenzoyl, 2,4-dimethylbenzyl, 2,4,6-trimethylbenzyl, 2-cryptomaterial, 3-cryptomaterial, 4-cryptomaterial, 2-methoxybenzyl,

3-methoxybenzyl, 4-methoxybenzyl, 4-ethoxybenzyl,

2-(3-methoxyphenyl)ethyl, 3,4-dimethoxybenzyl,

3,4,5-trimethoxybenzyl, 4-hydroxybenzyl, 3-hydroxybenzyl,

2-hydroxybenzyl, 2,4-dihydroxybenzyl, 3,4,5-trihydroxybenzoic,

2-methoxy-4-Chlorobenzyl, 3-methyl-5-tormentil,

2-(4-hydroxyphenyl)-1-methoxycarbonylethyl and

2-(4-chlorophenyl)-1-ethoxycarbonylethyl.

Examples of the lower alkylenediamine phenyl(lower)alkyl groups include:

alkylenediamine phenylaniline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group substituted in the phenyl ring one or not is how many of the above unbranched and branched C 1-4alkylenedioxy;

such as 3,4-methylenedioxybenzyl, 3,4-trimethylindolenine,

2-(2,3-atlanticcity)ethyl,

1-(3,4-trimethylenediamine)ethyl,

3-(2,3-tetramethyldisilane)propyl,

4-(3,4-methylenedioxyphenyl)butyl,

5-(2,3-atlanticcity)pencil,

6-(3,4-trimethylenediamine)hexyl,

1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, and

2-methyl-3-(3,4-atlanticcity)propyl.

Examples furyl(lower)alkyl groups include fenilalanina group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(2 - or 3-)furyl]methyl, 2-[(2 - or 3-)furyl]ethyl, 1-[(2 - or 3-)furyl]ethyl, 3-[(2 - or 3-)furyl]propyl, 4-[(2 - or 3-)furyl]butyl, 5-[(2 - or 3-)furyl]pentyl, 6-[(2 - or 3-)furyl]hexyl, 1,1-dimethyl-2-[(2 - or 3-)furyl]ethyl and 2-methyl-3-[(2 - or 3-)furyl]propyl.

Examples carbarnoyl(lower)alkyl groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups include:

carbamylcholine group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted by one or two h the s, selected from the group consisting of the above-described non-branched and branched C1-6the alkyl groups described above phenyl groups, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkyl groups;

such as carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl,

3-carbamoylethyl, 4-carbamoylmethyl, 5-carbamoylmethyl,

6-carbamoylethyl, 1,1-dimethyl-2-carbamoylethyl,

2-methyl-3-carbamoylmethyl, 2-(Nmethyl-Nphenylcarbamoyl)ethyl,

N(4-were)carbamoylmethyl,

2-[Nmethyl-N(3-were)carbarnoyl]ethyl,

N(2-were)carbamoylmethyl,

2-[Nethyl-N(3,4-dimetilfenil)carbarnoyl]ethyl,

N(2,4,6-trimetilfenil)carbamoylmethyl,

N,N-dimethylcarbamoyl, N,N-diphenylcarbamate,

Nmethyl-Nethylcarboxylate,Nmethylcarbamoylmethyl and

2-(Nmethylcarbamoyl)ethyl.

Examples imidazolyl(lower)alkyl groups, optionally substituted lower alkyl group by one or more members selected from the group consisting of carbamoyl group and lower alkoxycarbonyl groups include:

imidazolylalkyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally samisen the e in the lower alkyl group by one or more members, selected from the group consisting of carbamoyl group and alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup;

such as, in addition to the above imidazolyl(lower)alkyl groups,

1-carbarnoyl-2-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

1-methoxycarbonyl-2-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

1-carbarnoyl-1-[(1-, 2-, 4 - or 5-)imidazolyl]methyl,

1-etoxycarbonyl-1-[(1-, 2-, 4 - or 5-)imidazolyl]methyl,

1-carbarnoyl-3-[(1-, 2-, 4 - or 5-)imidazolyl]propyl,

1-npropoxycarbonyl-4-[(1-, 2-, 4 - or 5-)imidazolyl]butyl,

1-carbarnoyl-5-[(1-, 2-, 4 - or 5-)imidazolyl]pentyl and

1-tert-butoxycarbonyl-6-[(1-, 2-, 4 - or 5-)imidazolyl]hexyl.

Examples aminosilane lower alkyl groups, optionally substituted in each amino group of one or more lower alkyl groups include:

aminosilane unbranched and branched C1-6alkyl group, optionally substituted in the amino group with one or two unbranched and/or branched C1-6alkyl groups;

such as aminomethyl, 2-amino-ethyl, 1-amino-ethyl, 3-aminopropyl,

4-aminobutyl, 5-aminopentyl, 6-aminohexyl,

1,1-dimethyl-2-amino-ethyl, 2-methyl-3-aminopropyl, methylaminomethyl,

2-ethylaminomethyl, 3-npropylaminoethyl, 3-isopropylamino the l

4-nbutylaminoethyl, 5-nintellingencer,

6-nhexyleneglycol, dimethylaminoethyl,

2-diisopropylaminoethyl, 3-diisopropylaminoethyl,

(Nethyl-N-n-propylamino)methyl and

2-(Nmethyl-N-n-hexylamino)methyl.

Examples 2,3,4,5-tetrahydrofuryl groups, optionally substituted 2,3,4,5-tertrahydrofuran ring ring one or more oxopropyl include:

2,3,4,5-tetrahydropyridine group, optionally substituted 2,3,4,5-tertrahydrofuran ring ring one or two exography;

such as (2 - or 3-)2,3,4,5-tetrahydrofuryl, 2-oxo-(3-, 4 - or 5-)2,3,4,5-tetrahydrofuryl, 3-oxo-(2-, 4 - or 5-)2,3,4,5-tetrahydrofuryl and 2.5-dioxo-(3 - or 4-)2,3,4,5-tetrahydrofuryl.

Examples pyrrolidinyl(lower)alkyl group, optionally substituted in the pyrolidine ring by one or more lower alkyl groups include:

pyrrolidinylcarbonyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the pyrolidine ring one to three above unbranched and/or branched C1-6alkyl groups;

such as [(1-, 2 - or 3-)pyrrolidinyl]methyl,

2-[(1-, 2 - or 3-)pyrrolidinyl]ethyl,

1-[(1-, 2 - or 3-)pyrrolidinyl]ethyl,

3-[(1-, 2 - or 3-)pyrrolidinyl]propyl,

4-[(1-, 2 - or 3-)is pirrolidone]butyl,

5-[(1-, 2 - or 3-)pyrrolidinyl]pentyl,

6-[(1-, 2 - or 3-)pyrrolidinyl]hexyl,

1,1-dimethyl-2-[(1-, 2 - or 3-)pyrrolidinyl]ethyl,

2-methyl-3-[(1-, 2 - or 3-)pyrrolidinyl]propyl,

1-ethyl-[(2 - or 3-)pyrrolidinyl]methyl,

1-ethyl-[(2 - or 3-)pyrrolidinyl]methyl,

2-methyl-[(1-, 3-, 4 - or 5-)pyrrolidinyl]methyl,

3-npropyl-[(1-, 2-, 4 - or 5-)pyrrolidinyl]methyl,

1-nbutyl-[(2 - or 3-)pyrrolidinyl]methyl,

2-npentyl-[(1-, 3-, 4 - or 5-)pyrrolidinyl]methyl,

1-nhexyl-[(2 - or 3-)pyrrolidinyl]methyl,

1,2-dimethyl-[(3-, 4 - or 5-)pyrrolidinyl]methyl and

1,2,3-trimethyl-[(4 - or 5-)pyrrolidinyl]methyl.

Examples of phenoxy(lower)alkanoyl groups include phenoxyalkanoic group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, such as 2-phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyl, 5-Phenoxyethanol, 6-Phenoxyethanol, 2,2-dimethyl-3-phenoxypropionyl and 2-methyl-3-phenoxypropionyl.

Examples of morpholino(lower)alkyl groups include morpholinoethyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as [(2-, 3 - or 4-)morpholino]methyl,

2-[(2-, 3 - or 4-)morpholino]ethyl,

1-[(2-, 3 - or 4-)morpholino]ethyl,

3-[(2-, 3 - or 4-)morpholino]propyl,

4-[(2-, 3 - or 4-)morpholino]butyl,

p> 5-[(2-, 3 - or 4-)morpholino]pentyl,

6-[(2-, 3 - or 4-)morpholino]hexyl,

1,1-dimethyl-2-[(2-, 3 - or 4-)morpholino]ethyl and

2-methyl-3-[(2-, 3 - or 4-)morpholino]propyl.

Examples of pyridyl(lower)alkanoyl groups include pyridinoline group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, such as

2-[(2-, 3 - or 4-)pyridyl]acetyl,

3-[(2-, 3 - or 4-)pyridyl]propionic,

2-[(2-, 3 - or 4-)pyridyl]propionic,

4-[(2-, 3 - or 4-)pyridyl]butyryl,

5-[(2-, 3 - or 4-)pyridyl]pentanoyl,

6-[(2-, 3 - or 4-)pyridyl]hexanoyl,

2,2-dimethyl-3-[(2-, 3 - or 4-)pyridyl]propionic and

2-methyl-3-[(2-, 3 - or 4-)pyridyl]propionyl.

Examples taylorsville groups include 2-thienylboronic and 3-thienylboronic.

Examples thienyl(lower)alkanoyl groups include thienylallylamine group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, such as 2-[(2 - or 3-)thienyl]acetyl, 3-[(2 - or 3-)thienyl]propionyl, 2-[(2 - or 3-)thienyl]propionic, 4-[(2 - or 3-)thienyl]butyryl, 5-[(2 - or 3-)thienyl]pentanoyl, 6-[(2 - or 3-)thienyl]hexanol, 2,2-dimethyl-3-[(2 - or 3)thienyl]propionic and 2-methyl-3-[(2 - or 3-)thienyl]propionyl.

Examples cycloalkyl(lower)alkanoyl groups include C3-8cycloalkylcarbonyl group, where alcoholly fragment of the submitted is an unbranched or branched C 2-6alkanoyloxy group, such as 2-cyclopropylacetic,

2-cyclohexylethyl, 3-cyclopropylamine,

2-cyclobutylamine, 2-cyclopentylacetyl,

3-cyclopentylpropionyl, 4-cyclohexylstyrene,

5-cycloheptylmethyl, 6-cyclooctylamino,

2,2-dimethyl-3-cyclohexylpropionic and

2-methyl-3-cyclopropylamine.

Examples isoxazolecarboxylic groups, optionally substituted in isoxazoline ring by one or more lower alkyl groups include isoxazolecarboxylic group, optionally substituted in isoxazoline ring one or two unbranched and/or branched C1-6alkyl groups, such as (3-, 4 - or 5-)isoxazolidinone,

[3,5-dimethyl-4-isoxazolyl]carbonyl,

[3-ethyl-(4 - or 5-)isoxazolyl]carbonyl,

[4-npropyl-(3 - or 5-)isoxazolyl]carbonyl,

[5-nbutyl-(3 - or 4-)isoxazolyl]carbonyl,

[3-npentyl-(4 - or 5-)isoxazolyl]carbonyl and

[4-nhexyl-(3 - or 5-)isoxazolyl]carbonyl.

Examples pyrazinecarboxamide groups include 2-pyrazinecarboxamide.

Examples piperidinylcarbonyl groups, optionally substituted in piperidinium ring by one or more members selected from the group consisting of bentilee group and lower alkanoyl groups include:

piperidinylcarbonyl group, neoba is consequently replaced in piperidinium ring one to three members, selected from the group consisting of bentilee group described above unbranched and branched C1-6alkanoyl groups;

such as (1-, 2-, 3 - or 4-)piperidinylcarbonyl,

[1-acetyl-(2-, 3 - or 4-)piperidinyl]carbonyl,

[1-benzoyl-(2-, 3 - or 4-)piperidinyl]carbonyl,

[2-propionyl(1-, 3-, 5 -, or 6-)piperidinyl]carbonyl,

[3 butyryl-(1-, 2-, 5 -, or 6-)piperidinyl]carbonyl,

[4-pentanoyl-(1-, 2 - or 3-)piperidinyl]carbonyl,

[1-hexanoyl-(2-, 3 - or 4-)piperidinyl]carbonyl,

[1-acetyl-4-benzoyl-(2-, 3-, 5 -, or 6-)piperidinyl]carbonyl and

[1,2,4-triacetyl-(3-, 5 -, or 6-)piperidinyl]carbonyl.

Examples chromenickel groups include 2-chromenickel, 3-chromenickel, 4-chromenickel, 5-chromenickel, 6-chromenickel, 7-chromenickel and 8-chromenickel.

Examples isoindoline(lower)alkanoyl groups, optionally substituted in isoindoline the ring one or more oxopropyl include:

isoindoline(lower)alcoholnye group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, optionally substituted in isoindoline ring one or two exography;

such as 2-[(1-, 2-, 4 - or 5-)isoindoline]acetyl,

3-[(1-, 2-, 4 - or 5-)isoindoline]propionyl,

2-[(1-, 2-, 4 - or 5-)isoindoline]propionyl,

4-[(1-, 2-, 4 - or 5-isoindolyl]butyryl,

5-[(1-, 2-, 4 - or 5-)isoindoline]pentanoyl,

6-[(1-, 2-, 4 - or 5-)isoindoline]hexanoyl,

2,2-dimethyl-3-[(1-, 2-, 4 - or 5-)isoindoline]propionyl,

2-methyl-3-[(1-, 2-, 4 - or 5-)isoindoline]propionyl,

[1,3-dioxo-2-(2-, 4 - or 5-)isoindoline]acetyl and

[1-oxo-2-(2-, 3-, 4-, 5-, 6 - or 7-)isoindoline]acetyl.

Examples diazolidinyl(lower)alkanoyl groups, optionally substituted in thiazolidinone ring by one or more members selected from the group consisting of a carbonyl group and tocography include:

thiazolidinedione group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, optionally substituted in thiazolidinone ring by one or two members selected from the group consisting of a carbonyl group and tocography;

such as 2-[(2-, 3-, 4 - or 5-)diazolidinyl]acetyl,

3-[(2-, 3-, 4 - or 5-)diazolidinyl]propionyl,

2-[(2-, 3-, 4 - or 5-)diazolidinyl]propionyl,

4-[(2-, 3-, 4 - or 5-)diazolidinyl]butyryl,

5-[(2-, 3-, 4 - or 5-)diazolidinyl]pentanoyl,

6-[(2-, 3-, 4 - or 5-)diazolidinyl]hexanoyl,

2,2-dimethyl-3-[(2-, 3-, 4 - or 5-)diazolidinyl]propionyl,

2-methyl-3-[(2-, 3-, 4 - or 5-)diazolidinyl]propionyl,

[2 thioxo-4-oxo-2-(3 - or 5-)diazolidinyl]acetyl,

[2 thioxo-2-(3-, 4 - or 5-)diazolidinyl]acetyl,

[2-oxo-2-(3-, 4 - or 5-)diazolidinyl]acetyl,

[2,4-dicicco-2-(3 - or 5-)thiazo idini]acetyl and

[2,4-dioxo-2-(3 - or 5-)diazolidinyl]acetyl.

Examples piperidinyl(lower)alkanoyl groups include piperidinemethanol group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, such as

2-[(1-, 2-, 3 - or 4-)piperidinyl]acetyl,

3-[(1-, 2-, 3 - or 4-)piperidinyl]propionyl,

2-[(1-, 2-, 3 - or 4-)piperidinyl]propionyl,

4-[(1-, 2-, 3 - or 4-)piperidinyl]butyryl,

5-[(1-, 2-, 3 - or 4-)piperidinyl]pentanoyl,

6-[(1-, 2-, 3 - or 4-)piperidinyl]hexanoyl,

2,2-dimethyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propionyl and

2-methyl-3-[(1-, 2-, 3 - or 4-)piperidinyl]propionyl.

Examples of phenyl(lower)alkenylboronic groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

phenylacetylcarbinol group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as strikeball (trivial name: cinnamoyloxy group), 3-phenyl-2-propenylboronic, 4-phenyl-2-butylcarbamoyl,

4-phenyl-3-butylcarbamoyl, 5-phenyl-4-intercorporal,

5-phenyl-3-intercorporal, 6-phenyl-5-hexadecacarbonyl,

6-phenyl-4-hexadecacarbonyl, 6-phenyl-3-examinarlo the l

4-phenyl-1,3-butadienerubber,

6-phenyl-1,3,5-extrauniversal, 2-chlorthalidone,

3-(4-bromophenyl)-2-propenylboronic,

4-(3-forfinal)-2-butylcarbamoyl,

4-(2,4-dichlorophenyl)-3-butylcarbamoyl,

5-(2,4,6-tryptophanyl)-4-intercorporal,

5-(4-itfeel)-3-intercorporal,

6-(3-chlorophenyl)-5-hexadecacarbonyl,

6-(4-chlorophenyl)-4-hexadecacarbonyl,

6-(3,4-dichlorophenyl)-3-hexadecacarbonyl,

4-(3-chloro-4-forfinal)-1,3-butadienerubber and

6-(2,6-differenl)-1,3,5-extrauniversal.

Examples of phenyl(lower)alkenylboronic groups, optionally substituted in the phenyl ring by one or more lower alkylenedioxy include:

phenylacetylcarbinol group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, optionally substituted in the phenyl ring by one or more of the above non-branched and branched C1-4alkylenedioxy;

such as 3,4-methylenedioxyaniline,

3-(2,3-atlanticcity)-2-propenylboronic,

4-(3,4-trimethylhexanoyl)-2-butylcarbamoyl,

4-(2,3-tetramethyldisilane)-3-butylcarbamoyl,

5-(2,3-methylenedioxyphenyl)-4-intercorporal,

5-(3,4-atlanticcity)-3-intercorporal,

6-(2,3-trimethylene xifei)-5-hexadecacarbonyl,

6-(3,4-tetramethyldisilane)-4-hexadecacarbonyl,

6-(2,3-methylenedioxyphenyl)-3-hexadecacarbonyl,

4-(3,4-methylenedioxyphenyl)-1,3-butadienerubber and

6-(2,3-methylenedioxyphenyl)-1,3,5-extrauniversal.

Examples of pyridyl(lower)alkenylboronic groups include pyridylcarbonyl group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group,

such as 2-[(2-, 3 - or 4-)pyridyl]vinylcarbenes,

3-[(2-, 3 - or 4-)pyridyl]-2-propenylboronic,

4-[(2-, 3 - or 4-)pyridyl]-2-butylcarbamoyl,

4-[(2-, 3 - or 4-)pyridyl]-3-butylcarbamoyl,

5-[(2-, 3 - or 4-)pyridyl]-4-intercorporal,

5-[(2-, 3 - or 4-)pyridyl]-3-intercorporal,

6-[(2-, 3 - or 4-)pyridyl]-5-hexadecacarbonyl,

6-[(2-, 3 - or 4-)pyridyl]-4-hexadecacarbonyl,

6-[(2-, 3 - or 4-)pyridyl]-3-hexadecacarbonyl,

4-phenyl-1,3-butadienerubber and

6-[(2-, 3 - or 4-)pyridyl]-1,3,5-extrauniversal.

Examples of pyridylthio(lower)alkanoyl groups include pyridylmethylene group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group,

such as 2-[(2-, 3 - or 4-)pyridylthio]acetyl,

3-[(2-, 3 - or 4-)pyridylthio]propionyl,

2-[(2-, 3 - or 4-)pyridylthio]propionyl,

4-[(2-, 3 - or 4-)pyridylthio]butyryl,

5-[2-, 3 - or 4-)pyridylthio]pentanoyl,

6-[(2-, 3 - or 4-)pyridylthio]hexanoyl,

2,2-dimethyl-3-[(2-, 3 - or 4-)pyridylthio]propionyl and

2-methyl-3-[(2-, 3 - or 4-)pyridylthio]propionyl.

Examples indolinecarboxylic groups include 1-indolocarbazole, 2-indolocarbazole, 3-indolocarbazole, 4-indolocarbazole, 5-indolocarbazole, 6-indolocarbazole and 7-indolocarbazole.

Examples pyrrolidinedione groups include 2-pyrrolidinone and 3-pyrrolidinone.

Examples pyrrolidinylcarbonyl groups, optionally substituted in the pyrolidine ring one or more oxopropyl include pyrrolidinylcarbonyl group, optionally substituted in the pyrolidine ring one or two exography, such as (1-, 2 - or 3-)pyrrolidinylcarbonyl,

2-oxo-(1-, 3-, 4 - or 5-)pyrrolidinylcarbonyl,

3-oxo-(1-, 2-, 4 - or 5-)pyrrolidinylcarbonyl,

2.5 dioxo-(1 - or 3-)pyrrolidinylcarbonyl and

2,3-dioxo-(1-, 4 - or 5-)pyrrolidinylcarbonyl.

Examples benzofuranyl groups include 2-benzofuranyl, 3-benzofuranyl, 4-benzofuranyl, 5-benzofuranyl, 6-benzofuranyl and 7-benzofuranyl.

Examples indolyl(lower)alkanoyl groups include indolealkylamine group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group,

such to the 2-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]acetyl,

3-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]propionyl,

2-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]propionyl,

4-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]butyryl,

5-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]pentanoyl,

6-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]hexanoyl,

2,2-dimethyl-3-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]propionyl

and 2-methyl-3-[(1-, 2-, 3-, 4-, 5-, 6 - or 7-)indolyl]propionyl.

Examples benzothiadiazole groups include

2-benzothiazolinone, 3-benzothiazolinone,

4-benzotriazolyl, 5-benzotriazolyl,

6-benzotriazolyl and 7-benzothiazolinone.

Examples of phenyl(lower)alkanoyl groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

fenilalanina group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl,

4-phenylbutyl, 5-phenylpentane, 6-phenylhexanoic,

2,2-dimethyl-3-phenylpropionyl, 2-methyl-3-phenylpropionyl,

2-(4-forfinal)acetyl, 3-(2,5-differenl)propionyl,

2-(2,4-differenl)propionyl, 4-(3,4-differenl)butyryl,

5-(3,5-differenl)pentanoyl, 6-(2,6-differenl)hexanoyl,

2-(2-chlorophenyl)acetyl, 3-(3-chlorophenyl)propionyl

2-(4-chlorophenyl)propionyl, 4-(2,3-dichlorophenyl)propionyl,

5-(2,4-dichlorophenyl)pentanoyl, 6-(2,5-dichlorophenyl)hexanoyl,

2-(3,4-dichlorophenyl)acetyl, 3-(2,6-dichlorophenyl)propionyl,

2-(3-forfinal)propionyl, 4-(2-forfinal)butyryl,

5-(3-bromophenyl)pentanoyl, 6-(4-itfeel)hexanoyl,

2-(2-bromophenyl)acetyl, 3-(4-bromophenyl)propionyl,

2-(3,5-dichlorophenyl)propionyl, 4-(2,4,6-tryptophanyl)butyryl,

5-(3,4-differenl)pentanoyl, 6-(2-itfeel)hexanoyl,

2-(3-itfeel)acetyl, 3-(4-itfeel)propionyl,

2-(2,3-dibromophenyl)propionyl, 4-(2,4-diiodophenyl)butyryl and

2-(2,4,6-trichlorophenyl)acetyl.

Examples phenylsulfonyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxycarbonyl groups; ceanography; nitro; amino groups, optionally substituted by one or more lower alkanolamine groups; hydroxy-group; carboxyl group; a lower alkoxycarbonyl(lower)alkyl groups; halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms, and lower alkoxygroup, optionally substituted by one or more halogen atoms include:

phenylsulfonyl group, optionally substituted in the phenyl ring by one to five members selected from the group consisting of the above is use lower alkoxycarbonyl groups, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup; ceanography; the nitro group; the above-described amino groups, optionally substituted with one or two unbranched and/or branched C1-6alkanolamine groups; hydroxy-group; carboxyl group; the above alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup and alkyl fragment is an unbranched or branched C1-6alkyl group; halogen atoms; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms, and the above-described non-branched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms;

such as phenylsulfonyl, 4-methoxyphenylacetyl, 3-methoxyphenylacetyl, 2-methoxyphenylacetyl, 2-cryptomaterial, 3-cryptomaterial, 4-cryptomaterial, 3,4-dimethoxyphenylacetone, 2,5-dimethoxyphenylacetone, 2,4,6-trimethoxyvinylsilane, 4-nbutoxyethanol, 2-methoxy-5-chlorophenylsulfonyl, 2-methoxy-5-methylphenylsulfonyl,

2-methoxy-4-methylphenylsulfonyl, 4-chlorophenylsulfonyl,

3-chlorophenylsulfonyl, -chlorophenylsulfonyl,

4-perpenicular, 3-perpenicular,

2-perpenicular, 4-brompheniramine,

3-brompheniramine, 2-brompheniramine,

2,6-dichlorobenzenesulfonyl, 2,3-dichlorobenzenesulfonyl,

2,5-dichlorobenzenesulfonyl, 2,4-dichlorobenzenesulfonyl,

3,4-dichlorobenzenesulfonyl, 3,5-dichlorobenzenesulfonyl,

2-chloro-4-perpenicular, 2-bromo-5-chlorophenylsulfonyl,

2,5-differentiality, 2,4-differentiality,

2,6-differentiality, 3,4-differentiality,

2,4-dichloro-5-methylphenylsulfonyl, 2,4,5-triftorperasin,

2,3,4,5,6-pentafluorophenyl, 3-chloro-4-perpenicular,

2-chloro-6-methylphenylsulfonyl, 2,4-dichloro-6-methylphenylsulfonyl,

2-methyl-3-chlorophenylsulfonyl, 2-methyl-3-chlorophenylsulfonyl,

4-methyl-3-chlorophenylsulfonyl, 2-methyl-5-perpenicular,

2-methyl-4-brompheniramine, 2-fluoro-4-brompheniramine,

2,5-dimethyl-4-chlorophenylsulfonyl, 2-methylphenylsulfonyl,

3-methylphenylsulfonyl, 4-methylphenylsulfonyl,

2,5-dimethylbenzenesulfonyl, 2,4,6-trimethylphenylsulfonyl,

2,3,6-trimethyl-4-methoxybenzenesulfonyl,

4-tert-butylphenylmethyl, 4-ethylvanillin,

4-isopropylbenzenesulfonyl, 2-triftormetilfullerenov,

3-triftormetilfullerenov, 4-triftormetilfullerenov,

2-methoxycarbonylaminophenyl, 2-cyanovinylene the l

3-cyanophenylacetic, 4-cyanophenylacetic,

3-nitrophenyloctyl, 2-nitrophenyloctyl,

4-nitrophenyloctyl, 3-nitro-4-methylphenylsulfonyl,

3-nitro-6-methylphenylsulfonyl, 3-nitro-6-chlorophenylsulfonyl,

2-chloro-4-cyanophenylacetic, 4-acetylbenzenesulfonyl,

3-chloro-4-acetylbenzenesulfonyl,

2-hydroxy-3,5-dichlorobenzenesulfonyl, 2-hydroxyphenylacetic,

3-hydroxyphenylacetic, 4-hydroxyphenylethyl,

2-nitro-4-methoxyphenylacetyl, 3-carboxypenicillins,

4-carboxypenicillins, 2-carboxypenicillins,

4-(2-methoxycarbonylethyl)phenylsulfonyl,

3-carboxy-4-hydroxyphenylethyl, 3-aminophenylalanine,

2-aminophenylalanine and 4-aminophenylalanine.

Examples thienylmethyl groups, optionally substituted in the thiophene ring by one or more members selected from the group consisting of halogen atoms and lower alkoxycarbonyl groups include:

thienylmethyl group, optionally substituted in the thiophene ring with one to three members selected from halogen atoms and the above-described alkoxycarbonyl groups where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup;

such as (2 - or 3-)thienylmethyl,

[2-chloro-(3-, 4 - or 5-)thienyl]sulfonyl,

[2,3-dichloro-(4 or 5)thienyl]sulfonyl,

[2,5-dichloro-(3 - or 4-)thienyl]sulfonyl,

[2-bromo-(3-, 4 - or 5-)thienyl]sulfonyl,

[2-fluoro-(3-, 4 - or 5-)thienyl]sulfonyl,

(2,3,4-trichloro-5-thienyl)sulfonyl,

[2-methoxycarbonyl-(3-, 4 - or 5-)thienyl]sulfonyl,

[3-etoxycarbonyl-(2-, 4 - or 5-)thienyl]sulfonyl,

[3-npropoxycarbonyl-(2-, 4 - or 5-)thienyl]sulfonyl,

[2-tert-butoxycarbonyl-(3-, 4 - or 5-)thienyl]sulfonyl,

[2-npentyloxybenzoyl-(3-, 4 - or 5-)thienyl]sulfonyl,

[3-nhexyloxybenzoyl-(2-, 4 - or 5-)thienyl]sulfonyl,

[2,3-diethoxycarbonyl-(4 - or 5-)thienyl]sulfonyl and

[2-chloro-3-methoxycarbonyl-(4 - or 5-)thienyl]sulfonyl.

Examples hinolincarbonova groups include

2-chinaillon, 3-chinaillon, 4-chinaillon,

5-chinaillon, 6-chinaillon, 7-chinaillon and

8-chinaillon.

Examples imidazolylalkyl groups, optionally substituted in the imidazole ring by one or more lower alkyl groups include imidazolylalkyl group, optionally substituted in the imidazole ring with one to three above unbranched and branched C1-6alkyl groups, such as (1-, 2-, 4 - or 5-)imidazolylalkyl,

[1-methyl-(2-, 4 - or 5-)imidazolyl]sulfonyl,

[2-ethyl-(1-, 4 - or 5-)imidazolyl]sulfonyl,

[1-isopropyl-(2-, 4 - or 5-)imidazolyl]sulfone is,

[4-nbutyl-(1-, 2 - or 5-)imidazolyl]sulfonyl,

[5-npentyl-(1-, 2 - or 4-)imidazolyl]sulfonyl,

[1-nhexyl-(2-, 4 - or 5-)imidazolyl]sulfonyl,

[1,2-dimethyl-(4 - or 5-)imidazolyl]sulfonyl and

(1,2,4-trimethyl-5-imidazolyl)sulfonyl.

Examples phenylsulfonyl groups, optionally substituted in the phenyl ring by one or more lower alkylenedioxy include phenylsulfonyl group, optionally substituted in the phenyl ring by one to three above unbranched and branched C1-4alkylenedioxy, such as

(3,4-atlanticcity)sulfonyl,

(2,3-methylenedioxyphenyl)sulfonyl,

(3,4-trimethylenediamine)sulfonyl and

(2,3-tetramethyldisilane)sulfonyl.

Examples of the lower alkanesulfonyl groups include unbranched and branched C2-6alkanesulfonyl group containing one to three double bonds, such as vinylsulphonyl,

1-propylsulfonyl, 1-methyl-1-propylsulfonyl,

2-methyl-1-propylsulfonyl, 2-propylsulfonyl,

2-butylsulfonyl, 1-butanesulfonyl, 3-butylsulfonyl,

2-pentanesulfonic, 1-pentanesulfonic, 3-pentanesulfonic,

4-pentanesulfonic, 1, 3-butadienestyrene,

1,3-pentadiagonal, 2-penten-4-vinylsulphonyl,

2-hexanesulfonic, 1-hexanesulfonic, 5-GE is similartony,

3-hexanesulfonic, 4-hexanesulfonic,

3,3-dimethyl-1-propylsulfonyl, 2-ethyl-1-propylsulfonyl,

1,3,5-ekstrasistoliei, 1,3-hexadecanesulfonyl and

1,4-hexadecanesulfonyl.

Examples cycloalkylation lower alkylsulfonyl groups include C3-8cycloalkylation alkylsulfonyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as cyclopropanesulfonyl, cyclohexanesulfonyl,

2-cyclopropanesulfonyl, 1-cyclobutanecarbonyl,

cyclopentylmethyl, 3-cyclopentylpropionyl,

4-cyclohexanesulfonyl, 5-cycloheptylmethyl,

6-cyclooctylmethyl,

1,1-dimethyl-2-cyclohexanesulfonyl and

2-methyl-3-cyclopropanesulfonyl.

Examples 3,4-dihydro-2H-1,4-benzocaineenthol groups, optionally substituted 3,4-dihydro-2H-1,4-benzoxazinone ring by one or more lower alkyl groups include 3,4-dihydro-2H-1,4-benzoxazolinone group, optionally substituted in the 3,4-dihydro-2H-1,4-benzoxazinone ring one to three above unbranched and/or branched C1-6alkyl groups,

such as (2-, 3-, 4-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazinones,

[4-methyl-(2-, 3-, 5-, 6-, 7-or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[5-ethyl-(2-, 3-, 4-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[6-npropyl-(2-, 3-, 4-, 5-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[7-nbutyl-(2-, 3-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[8-npentyl-(2-, 3-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[2-nhexyl-(3-, 4-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[3-methyl-(2-, 4-, 5-, 6-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl,

[4,6-dimethyl-(2-, 3-, 5-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl and

[4,5,6-trimethyl-(2-, 3-, 7 - or 8-)3,4-dihydro-2H-1,4-benzoxazine]sulfonyl.

Examples pyrazolecontaining groups, optionally substituted in the pyrazol ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups include:

pyrazolecarboxylate group, optionally substituted in the pyrazol ring one to three members selected from the group consisting of halogen atoms and the above-described non-branched and branched C1-6alkyl groups;

such as (1-, 3-, 4 - or 5-)personalality,

(1,3-dimethyl-5-chloro-4-pyrazolyl)sulfonyl,

[1-ethyl-(3-, 4 - or 5-)pyrazolyl]sulfonyl,

[3-npropyl-(1-, 4 - or 5-)pyrazolyl]sulfonyl,

[4-nbutyl-(3-, 4 - or 5-)pyrazolyl]sulfonyl,

[5-npentyl-(1-, 3 - or 4-)pyrazolyl]sulfonyl,

[1-is-is hexyl-(3-, 4 - or 5-)pyrazolyl]sulfonyl,

[1,3-dimethyl-(4 - or 5-)pyrazolyl]sulfonyl,

(1,3,5-trimethyl-4-pyrazolyl)sulfonyl,

[3-bromo-(1-, 4 - or 5-)pyrazolyl]sulfonyl,

[4-fluoro-(1-, 3 - or 5-)pyrazolyl]sulfonyl,

[5-iodine-(1-, 3 - or 4-)pyrazolyl]sulfonyl,

[3,4-dichloro-(1 - or 5-)pyrazolyl]sulfonyl and

(3,4,5-trichloro-4-pyrazolyl)sulfonyl.

Examples isoxazolecarboxylic groups, optionally substituted in isoxazoline ring by one or more lower alkyl groups include isoxazolecarboxylic group, optionally substituted in isoxazoline ring one or two described above unbranched and/or branched C1-6alkyl groups, such as

(3-, 4 - or 5-)isoxazolidinone,

(3,5-dimethyl-4-isoxazolyl)sulfonyl,

[3-methyl-(4 - or 5-)isoxazolyl]sulfonyl,

[3-ethyl-(4 - or 5-)isoxazolyl]sulfonyl,

[4-npropyl-(3 - or 5-)isoxazolyl]sulfonyl,

[5-nbutyl-(3 - or 4-)isoxazolyl]sulfonyl,

[3-npentyl-(4 - or 5-)isoxazolyl]sulfonyl and

[4-nhexyl-(3 - or 5-)isoxazolyl]sulfonyl.

Examples triazolylmethyl groups, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and amino groups, and each Deputy for amino optionally substituted by one linescale lower alkanolamine groups, include:

triazolylmethyl group, optionally substituted in the thiazole ring with one or two members selected from the group consisting of the above-described unbranched or branched C1-6the alkyl groups described above amino groups, optionally substituted with one or two unbranched and/or branched C1-6alkanolamine groups;

such as (2-, 4 - or 5-)triazolylmethyl,

(2-acetylamino-4-methyl-5-thiazolyl)sulfonyl,

[2-ethyl-(4 - or 5-)thiazolyl]sulfonyl,

[4-npropyl-(2 - or 5-)thiazolyl]sulfonyl,

[5-nbutyl-(2 - or 4-)thiazolyl]sulfonyl,

[2-npentyl-(4 - or 5-)thiazolyl]sulfonyl,

[4-nhexyl-(2 - or 5-)thiazolyl]sulfonyl,

(2,4-dimethyl-5-thiazolyl)sulfonyl,

[2-amino-(4 or 5)thiazolyl]sulfonyl,

[2 formylamino-(4 - or 5-)thiazolyl]sulfonyl,

[4-npropionamido-(2 - or 5-)thiazolyl]sulfonyl,

[5-nbucillamine-(2 - or 4-)thiazolyl]sulfonyl,

[2-npentanediamine-(4 - or 5-)thiazolyl]sulfonyl,

[4-nhexanamine-(2 - or 5-)thiazolyl]sulfonyl,

(2,4-diacetyl-5-thiazolyl)sulfonyl and

[2-(N,N-diacetylamino)-(4 - or 5-)thiazolyl]sulfonyl.

Examples of phenyl(lower)alkylsulfonyl groups include mono - and diphenylethylene group, where the alkyl fragment is an unbranched or branched C 1-6alkyl group, such as benzylmethyl,

1-penetrameter, 2-penetrameter, 3-phenylpropylamine,

2-phenylpropionyl, 4-phenylmethylsulfonyl,

5-phenylmethylsulfonyl, 4-phenylmethylsulfonyl,

6-phenylhexanenitrile, 2-methyl-3-phenylpropylamine,

1,1-dimethyl-2-phenylethylamine,

1,1-dimethyl-1-phenylmethylsulfonyl, 1,1-diphenylmethylsilane,

2,2-diphenylethylamine, 3,3-diphenylpropylamine and

1,2-diphenylethylamine.

Examples of phenyl(lower)alkanesulfonyl groups include:

phenylalkylamine group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as steelsurface, 3-phenyl-2-propylsulfonyl,

4-phenyl-2-butylsulfonyl, 4-phenyl-3-butylsulfonyl,

5-phenyl-4-pentanesulfonic, 5-phenyl-3-pentanesulfonic,

6-phenyl-5-hexanesulfonic, 6-phenyl-4-hexanesulfonic,

6-phenyl-3-hexanesulfonic, 4-phenyl-1,3-butadienestyrene,

6-phenyl-1,3,5-ekstrasistoliei, 2-charcterisation,

3-(4-bromophenyl)-2-propanesulfonyl,

4-(3-forfinal)-2-butylsulfonyl,

4-(2,4-dichlorophenyl)-3-butylsulfonyl,

5-(2,4,6-tryptophanyl)-4-pentenal who were radioactive,

5-(4-itfeel)-3-pentanesulfonic,

6-(3-chlorophenyl)-5-hexanesulfonic,

6-(4-chlorophenyl)-4-hexanesulfonic,

6-(3,4-dichlorophenyl)-3-hexanesulfonic,

4-(3-chloro-4-forfinal)-1, 3-butadienestyrene and

6-(2,6-differenl)-1,3,5-ekstrasistoliei.

Examples naphthalocyanine groups include 1-naphthaleneboronic and 2-naphthaleneboronic.

Examples of the lower alkyloxyalkyl groups include alkyloxyaryl group, where alkynylaryl fragment is an unbranched or branched C2-6alkylamino group, such as ethinylestradiol,

2-propenylboronic, 2-butyloxycarbonyl,

3-butyloxycarbonyl, 1-methyl-2-propenylboronic,

2-intenrational and 2-hexyloxybenzoyl.

Examples of the lower altneratively groups include altneratively group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, such as vinyloxycarbonyl, 1-propenylboronic,

1-methyl-1-propenylboronic, 2-methyl-1-propenylboronic,

2-propenylboronic, 2-butyloxycarbonyl,

1-butyloxycarbonyl, 3-butyloxycarbonyl,

2-interracialanal, 1-interracialanal,

3-interracialanal, 4-pentyloxide the sludge

1,3-butadienestyrene, 1,3-pentadienylboronic,

2-penten-4-indoxacarb, 2-hexadecacarbonyl,

1-hexadecacarbonyl, 5-hexadecacarbonyl,

3-hexadecacarbonyl, 4-hexadecacarbonyl,

3,3-dimethyl-1-propenylboronic,

2-ethyl-1-propenylboronic, 1,3,5-extrauniversal,

1,3-hexadecacarbonyl and 1,4-hexadecacarbonyl.

Examples of phenyl(lower)alkoxy-substituted lower alkoxycarbonyl groups include fenilalaninammonii alkoxycarbonyl group, where each of the two alkoxy fragments represents an unbranched or branched C1-6alkoxygroup, such as phenylmethanesulfonyl,

2-(phenylmethoxy)etoxycarbonyl, 1-(phenylmethoxy)etoxycarbonyl,

3-(phenylmethoxy)propoxycarbonyl,

4-(phenylmethoxy)butoxycarbonyl,

5-(phenylmethoxy)pentyloxybenzoyl,

6-(phenylmethoxy)hexyloxybenzoyl,

1,1-dimethyl-2-(phenylmethoxy)etoxycarbonyl,

2-methyl-3-(phenylmethoxy)propoxycarbonyl,

1-(2-phenylethane)etoxycarbonyl,

2-(1-phenylethane)etoxycarbonyl,

3-(3-phenylpropoxy)propoxycarbonyl,

4-(4-phenylmethoxy)butoxycarbonyl,

5-(5-phenylmethoxy)pentyloxybenzoyl,

6-(6-phenylhexanoic)hexyloxybenzoyl,

(1,1-dimethyl-2-phenylethane)methoxycarbonyl and

3-(2-methyl-3-fenil is epoxy)propoxycarbonyl.

Examples cycloalkylcarbonyl groups, optionally substituted in cycloalkene ring by one or more lower alkyl groups include:

cycloalkylcarbonyl group, where cycloalkane-fragment represents a C3-8cycloalkanes, optionally substituted in cycloalkene ring one to three above unbranched and branched C1-6alkyl groups;

such as cyclopropanecarbonyl, cyclobutanecarbonyl,

cyclopentanecarbonyl, cyclohexyloxycarbonyl,

cyclohexyloxycarbonyl, cyclooctylmethyl,

3-methyl-6-isopropylcyclopentadienyl,

2-ethylcyclohexylamine, 2-npropylcyclohexanone,

3-nbutylcyclohexylamine,

3-npentylcyclohexanecarboxylic, 2-methylcyclopentadienyl

and 2,3,6-trimethylcyclohexylamine.

Examples isoxazolyl groups, optionally substituted in isoxazoline ring by one or more lower alkyl groups include isoxazolidine group, optionally substituted in isoxazoline ring one or two unbranched and/or branched C1-6alkyl groups, such as (3-, 4 - or 5-)isoxazolyl,

5-methyl-(3 - or 4-)isoxazolyl, 3,5-dimethyl-4-isoxazolyl,

3-ethyl-(4 - or 5-)isoxazol the sludge

4-npropyl-(3 - or 5-)isoxazolyl,

5-nbutyl-(3 - or 4-)isoxazolyl,

3-npentyl-(4 - or 5-)isoxazolyl and

4-nhexyl-(3 - or 5-)isoxazolyl.

Examples 5-7-membered saturated heterocyclic rings formed by R6and R7while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic ring optionally contains one or more additional heteroatoms, include:

5-7-membered saturated heterocyclic ring formed from R6and R7while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic group optionally contains one or more additional heteroatoms selected from oxygen atom, sulfur atom and nitrogen atom;

such as pyrrolidine, piperazine, piperidine, morpholine, thiomorpholine, homopiperazine, homopiperazin, imidazolidin, thiazolidin, isothiazolin, oxazolidin, isoxazolidine, isothiazolines and pyrazolidine.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; lower alkyl groups optionally substituted by one or more atom of the mi halogen; ceanography and hydroxy-group, include:

phenyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms; the above-described non-branched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms; the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; ceanography and hydroxy-group;

such as phenyl, 4-isopropylphenyl, 3-isopropylphenyl, 2-isopropylphenyl, 4-tert-butylphenyl, 4-were, 3-were, 2nd were, 2,3-dimetilfenil, 2,4-dimetilfenil, 3, 5dimethylphenyl, 2,4,6-trimetilfenil, 4-methyl-3-methoxyphenyl, 4-triptoreline, 3-triptoreline, 2-triptoreline, 4-methyl-3-chlorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 2-forfinal, 3-forfinal, 4-forfinal, 3-bromophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,4,5-trichlorophenyl, 2,4,6-tryptophanyl, 3,5-differenl, 3-chloro-4-forfinal,

2-chloro-5-forfinal, 3-fluoro-4-methoxyphenyl, 3-chloro-4-methoxyphenyl, 3-chloro-4-hydroxyphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2,4-acid, 3,4-acid, 2,4,6-trimethoxyphenyl, 2-methoxy-5-chlorophenyl, 4-ethoxyphenyl, 4-trifloromethyl, 3-trifloromethyl, 2-trifloromethyl, 3-methoxy-5-trifluoromethyl phenyl, 2-cyanophenyl, 3-CANopen is l, 4-cyanophenyl, 3-hydroxyphenyl, 2-hydroxyphenyl and 4-hydroxyphenyl.

Examples of phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more halogen atoms include:

mono - and diphenylethylene group, allyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in each phenyl ring by one to three halogen atoms;

such as benzyl, 1-phenethyl, 2-phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil, 6-phenylhexa, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl, 1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl, 1,2-diphenylether, 4-Chlorobenzyl, 2-Chlorobenzyl, 3-Chlorobenzyl, 2-tormentil, 3-tormentil, 4-tormentil, 2,3-dichlorobenzyl and 2,4,6-triptorelin.

Examples of phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more halogen atoms include:

fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the phenyl ring by one to three halogen atoms;

such as benzyloxy, 2-phenylethane, 1 venlafaxi,

3 phenylpropoxy, 4-phenylbutane, 5-phenylpentane,

6 phenylhexanoic, 1,1-dimethyl-2-phenylethane,

2-methyl-3-phenylpropoxy, 4-chlorbenzyl the si, 2 Chlorobenzilate,

3 Chlorobenzilate, 2-forbindelse, 3 fermentelos,

4 fermentelos, 2,4-dibromobenzoate and

2,4,6-triterpenic.

Examples carbarnoyl(lower)alkyl groups, optionally substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups include:

carbamylcholine group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted by one or two members selected from the group consisting of phenyl group and the above-described non-branched and branched C1-6alkyl groups;

such as carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl,

3-carbamoylethyl, 4-carbamoylmethyl, 5-carbamoylmethyl,

6-carbamoylethyl, 1,1-dimethyl-2-carbamoylethyl,

2-methyl-3-carbamoylmethyl, 2-(Nmethyl-Nphenylcarbamoyl)ethyl,

Nphenylcarbamoyl, 2-(N,Ndimethylcarbamoyl)ethyl,

3-(Nphenylcarbamoyl)propyl, 2-(Nethyl-Nphenylcarbamoyl)ethyl,

N,N-dimethylcarbamoyl,Nmethyl-Nethylcarboxylate,

Nmethylcarbamoylmethyl and 2-(Nmethylcarbamoyl)ethyl.

Examples of phenyl(lower)alkylidene groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

phenylalkylamine group, where alkylidene fragment is an unbranched or branched C1-6alkylidene group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as phenylmethylene, fenretinide, phenylpropylamine,

phenylisopropylamine, panelbuilder, phenylindolizine,

panelscreen, 2-chlorophenylglycine, 3-chlorophenylglycine,

4-chlorophenylglycine, 2-performation,

3-performation, 4-performation,

2-bromophenylacetate, 3-bromophenylacetate,

4-bromophenylacetate, 2-idgenerator,

2,3-dichlorophenylamino, 2,4-diferenzenmethoden,

2,4,6-trichloropyridin, 2,3,5-tryptophannutrition and

2-fluoro-4-chlorophenylglycine.

Examples of phenyl(lower)alkoxycarbonyl groups include generalquartiermeister group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, such as benzyloxycarbonyl,

2-fenilalaninammonii, 1-fenilalaninammonii,

3-phenylpropionyl, 4-privateserver,

5-phenylmethylsulphonyl, 6-vanillacracker,

1,1-dimethyl-2-fenilalaninammonii and

2-methyl-3-phenylpropionyl.

Examples peredelnyh groups, optionally substituted in the pyridine ring with one or a number of the mi members, selected from the group consisting of ceanography and lower alkyl groups include:

peredelnye group, optionally substituted in the pyridine ring with one to three members selected from the group consisting of ceanography described above unbranched and branched C1-6alkyl groups;

such as (2-, 3 - or 4-)pyridyl,

2-methyl-(3-, 4-, 5 -, or 6-)pyridyl,

3-methyl-(2-, 4-, 5 -, or 6-)pyridyl, 4-methyl-(2 - or 3-)pyridyl,

2-cyano-(3-, 4-, 5 -, or 6-)pyridyl,

3-cyano-(2-, 4-, 5 -, or 6-)pyridyl, 4-cyano-(2 - or 3-)pyridyl,

2,3-dimethyl-(4-, 5 -, or 6-)pyridyl,

3,4,5-trimethyl-(2 - or 6-)pyridyl,

2,4-dicyano-(3-, 5 -, or 6-)pyridyl,

2,4,5-Tiziano-(3 - or 6-)pyridyl and

2-methyl-4-cyano-(3-, 5 -, or 6-)pyridyl.

Examples of 1,3-DIOXOLANYL(lower)alkyl groups include 1,3-dioxyalkylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as

[(2 - or 4-)1,3-DIOXOLANYL]methyl,

2-[(2 - or 4-)1,3-DIOXOLANYL]ethyl,

1-[(2 - or 4-)1,3-DIOXOLANYL]ethyl,

3-[(2 - or 4-)1,3-DIOXOLANYL]propyl,

4-[(2 - or 4-)1,3-DIOXOLANYL]butyl,

1,1-dimethyl-2-[(2 - or 4-)1,3-DIOXOLANYL]ethyl,

5-[(2 - or 4-)1,3-DIOXOLANYL] pentyl,

6-[(2 - or 4-)1,3-DIOXOLANYL]hexyl,

1-[(2 - or 4-)1,3-DIOXOLANYL]isopropyl and

2-methyl-3-[(1-, 2 - or 4-)1,3-DIOXOLANYL]propyl.

Examples 5-8-membered saturated, heterocyclic the ski rings, formed from R8and R9while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic ring optionally contains one or more additional heteroatoms, include:

5-8-membered saturated heterocyclic ring formed from R8and R9while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic ring optionally contains one or more additional heteroatoms selected from oxygen atom, sulfur atom and nitrogen atom;

such as pyrrolidine, piperazine, piperidine, morpholine, thiomorpholine, imidazolidin, thiazolidin, isothiazolin, oxazolidin, isoxazolidine, isothiazolin, pyrazolidine, peligrosas and perhydroanthracene.

Examples octahedral[1,2-a]personilnya groups, optionally substituted in pyrazinium ring by one or more lower alkyl groups include octahedral[1,2-a]personilnya group, optionally substituted in pyrazinium ring one to three unbranched and/or branched C1-6alkyl groups.

Examples 8-azabicyclo[3.2.1]artelinic groups, optionally substituted 8-azabicyclo[3.2.1]octiles group of one or more phenoxypropane, where each phenoxy-Deputy long is Ino substituted in the phenyl ring by one or more halogen atoms, include 8-azabicyclo[3.2.1]aktalnye group, optionally substituted 8-azabicyclo[3.2.1]octiles group of one to three phenoxypropane, where each phenoxy-Deputy optionally substituted in the phenyl ring by one to three halogen atoms.

Examples of 5 - or 6-membered saturated heterocyclic rings formed by R11and R12or R13and R14while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic ring optionally contains one or more additional heteroatoms, include:

5 - or 6-membered saturated heterocyclic ring formed from R11and R12or R13and R14while associating them with each other, together with the nitrogen atom to which they are attached, and the heterocyclic ring optionally contains one or more additional heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom;

such as pyrrolidine, piperazine, piperidine, morpholine, thiomorpholine, imidazolidin, thiazolidin, isothiazolin, oxazolidin, isoxazolidine, isothiazolines and pyrazolidine.

Examples of phenyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or some of the atoms and halogen; lower alkylthio; lower alkoxygroup, optionally substituted by one or more halogen atoms; halogen atoms; phenyl groups; lower alkylamino; ceanography; fenoxaprop; cycloalkyl groups; pyrrolidinyl groups, optionally substituted by one or more exography; 1,2,3,4-tetrahydroisoquinolinium groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; thiazolidine groups, optionally substituted by one or more phenyl groups; carbamoyl groups; phenyl(lower)alkoxygroup; lower alkylsulfonamides; inlinegroup, optionally substituted one or more halogen atoms; phenyl(lower)alkyl groups and replacement of the lower alkyl groups include:

phenyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of unbranched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; an unbranched and branched C1-6alkylthio; unbranched and branched C1-6alkoxygroup, neobyazatel is substituted by one to three halogen atoms; of halogen atoms; phenyl groups; amino groups, optionally substituted with one or two unbranched and/or branched C1-6alkyl groups; ceanography; fenoxaprop; C3-8cycloalkyl groups; pyrrolidinyl groups, optionally substituted by one or two exography; 1,2,3,4-tetrahydroisoquinolinium groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one to three unbranched and/or branched C1-6alkyl groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one to three unbranched and/or branched C1-6alkyl groups; thiazolidine groups, optionally substituted with one to three phenyl groups; carbamoyl group; fenilalanina, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup; unbranched and branched C1-6alkylsulfonamides; inlinegroup, optionally substituted with one to three halogen atoms; phenylalkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, and replacement alkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group substituted by one or t is EMA hydroxy groups;

such as (2-, 3 - or 4-)triptoreline,

(2-, 3 - or 4-)methylthiophenyl,

(2-, 3 - or 4-)trifloromethyl,

(2-, 3 - or 4-)ethylphenyl, (2-, 3 - or 4-)propylphenyl,

(2-, 3 - or 4-)butylphenyl, (2-, 3 - or 4-)pentylphenol,

(2-, 3 - or 4-)hexylphenyl, (2-, 3 - or 4-)isopropylphenyl,

(2-, 3 - or 4-)chlorophenyl, (2-, 3 - or 4-)forfinal,

(2-, 3 - or 4-)phenylphenyl, (2-, 3 - or 4-)dimethylaminophenyl,

(2-, 3 - or 4-)cyanophenyl, (2-, 3 - or 4-)phenoxyphenyl,

(3,4-, 2,3-, 2,6 - or 3,5-)dimetilfenil,

(3,4-, 2,3-, 2,6 - or 3,5-)differenl, 2-chloro-4-were,

(2-, 3 - or 4-)cyclohexylphenol, (2-, 3 - or 4-)benzyloxyphenyl,

(2-, 3 - or 4-)methylsulfonylmethane,

(2-, 3 - or 4-)anilinophenol,

(3,4-, 2,3-, 2,6 - or 3,5-)acid,

3-chloro-4-methoxyphenyl, 3-chloro-4-were,

3-methoxy-5-triptoreline, 2-chloro-5-triptoreline,

2-chloro-6-cyanophenyl, 2-chloro-5-carbamoylmethyl,

(2-, 3 - or 4-)phenylmethylene,

(2-, 3 - or 4-)pyrrolidineethanol,

(2-, 3 - or 4-)[(1-, 2-, 3 - or 4-)(1,2,3,4-tetrahydroisoquinoline)]phenyl,

(2-, 3 - or 4-)[(1-, 2-, 3 - or 4-)(6-methyl-1,2,3,4-tetrahydromyrcenol)]phenyl,

(2-, 3 - or 4-)(4-foronline)phenyl,

(2-, 3 - or 4-)[4-methyl-1-(1,2,3,4-tetrahydroquinoxaline)carbonyl]phenyl and

(2-, 3 - or 4-)[(4 - or 5-)phenylthiazole-2-yl]phenyl.

Examples of phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members of wybrand the mi group, consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; halogen atoms and phenyl groups include:

phenylaniline group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of unbranched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; an unbranched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms; halogen atoms and phenyl groups;

such as benzyl, 1-phenethyl, 2-phenethyl, 3-phenylpropyl,

2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil,

6-phenylhexa, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl,

1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl,

1,2-diphenylether, 4-Chlorobenzyl, 2-Chlorobenzyl, 3-Chlorobenzyl,

3-tormentil, 4-tormentil, (2 - or 4-)bromobenzyl,

2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 3-chloro-4-tormentil,

2,4,6-triptorelin, 3-trifloromethyl, 4-trifloromethyl,

2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-tert-butylbenzyl,

2,4-dimethylbenzyl, 2,4,6-trimethylbenzyl is l, 2-phenylbenzyl,

3-phenylbenzyl, 4-phenylbenzyl, 2,4-diphenylmethyl,

2,4,6-triphenylbenzene, 2-cryptomaterial,

3-cryptomaterial, 4-cryptomaterial,

3-chloro-4-deformational, 4-chloro-3-trifloromethyl,

2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl,

3,4-dimethoxybenzyl, 3,4,5-trimethoxybenzyl,

2-(4-methoxyphenyl)ethyl, 2-(2-methoxyphenyl)ethyl and

2-(4-chlorophenyl)ethyl.

Examples of the lower alkyl substituted amino(lower)alkyl groups include:

aminoalkyl group, where the alkyl fragment is an unbranched or branched C1-6alkyl group containing amino group of one or two unbranched and/or branched C1-6alkyl groups;

such asNmethylaminomethyl,N,N-diethylaminomethyl,

N,N-di-npropylaminoethyl,N,N-diisopropylaminoethyl,

3-(N,N-dimethylamino)propyl, 4-(N,N-dimethylamino)butyl,

5-(N,N-dimethylamino)pentyl and 6(N,N-dimethylamino)hexyl.

Examples pyrazinyl(lower)alkyl group, optionally substituted in pyrazinium ring by one or more lower alkyl groups include:

personalily group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in pyrazinium ring the ne-three unbranched and/or branched C 1-6alkyl groups;

such as (2 - or 3-)personality, (1 - or 2-)(2 - or 3-pyrazinyl)ethyl, 3-(2 - or 3-)personalbrain, 4-(2 - or 3-)personilty, 5-(2 - or 3-)personality, 6-(2 - or 3-)personalysis, 2-methyl-5-personality, (1 - or 2-)(2-methyl-5-pyrazinyl)ethyl, 3-(2-methyl-5-pyrazinyl)propyl, 4-(2-ethyl-5-pyrazinyl)butyl, 5-(2-ethyl-5-pyrazinyl)pentyl and 6-(2-methyl-5-pyrazinyl)hexyl.

Examples pyrazolyl(lower)alkyl group, optionally substituted in pyrazolinone ring by one or more lower alkyl groups include:

personially group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in pyrazolinone ring one to three unbranched and/or branched C1-6alkyl groups;

such as (3-, 4 - or 5-)parasailer,

(1 - or 2-)(3-, 4 - or 5-)persilylated,

3-(3-, 4 - or 5-)pyrazolylborate,

4-(3-, 4 - or 5-)pyrazolylborate,

5-(3-, 4 - or 5-)pyrazolidine,

6-(3-, 4 - or 5-)pyrazolines,

[1-methyl-(3-, 4 - or 5-)pyrazolyl]methyl,

[1,5-dimethyl-(3 - or 4-)pyrazolyl]methyl and

[1,5-dimethyl-(3 - or 4-)pyrazolyl]ethyl.

Examples piperidinyl groups, optionally substituted in piperidinium ring by one or more members selected from the group consisting of lower alkyl groups; bentilee gr is PPI and phenyl(lower)alkyl groups, optionally substituted in the phenyl ring by one or more members selected from halogen atoms and lower alkyl groups include:

piperidinyl group, optionally substituted in piperidinium ring one to three members selected from the group consisting of unbranched and branched C1-6alkyl groups; bentilee group and a phenyl(lower)alkyl groups, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms and unbranched and branched C1-6alkyl groups;

such asNmethyl-(2-, 3 - or 4-)piperidinyl,

Nethyl-(2-, 3 - or 4-)piperidinyl,

N-n-propyl-(2-, 3 - or 4-)piperidinyl,

Nbenzoyl-(2-, 3 - or 4-)piperidinyl,

1-benzyl-4-piperidinyl, 1-phenylethyl-4-piperidinyl,

1-(2-, 3 - or 4-)CHLOROFORMATES-4-piperidinyl,

1-(2-, 3 - or 4-)methylphenylethyl-4-piperidinyl,

1,2,3-trimethyl-(4-, 5 -, or 6-)piperidinyl,

1-benzyl-3-methyl-(2-, 4-, 5 -, or 6-)piperidinyl and

1-benzoyl-2-benzyl-(3-, 4-, 5 -, or 6-)piperidinyl.

Examples 3,4-dihydrocarbamazepine groups, optionally substituted by one or more lower alkyl groups include 3,4-dihydrocarbamazepine group, optional samisen the e one-three unbranched and/or branched C 1-6alkyl groups, such as 3,4-dihydro-(5-, 6-, 7 - or 8-)carbonsteel and (6-, 7 - or 8-)methyl-3,4-dihydro-5-carbonsteel.

Examples finalising groups, optionally substituted by one or more lower alkyl groups include chinoline group, optionally substituted one to three unbranched and/or branched C1-6alkyl groups, such as (2-, 3-, 4-, 5-, 6-, 7 - or 8-)hinely and 2-methyl-4-chinolin.

Examples carbazolyl groups, optionally substituted by one or more lower alkyl groups include carbazolyl group, optionally substituted one to three unbranched and branched C1-6alkyl groups, such asNmethyl-(2-, 3-, 4 - or 5-)carbazolyl andNethyl-(2-, 3-, 4 - or 5-)carbazolyl.

Examples of phenyl lower allylcarbamate(lower)alkyl groups include phenylalkylamine group, where each of the two alkyl fragments represents an unbranched or branched C1-6alkyl group, such as

phenylmethylsulphonyl, (1 - or 2-)phenylethylamine,

(1 or 2)fenilatilmalonamid,

3-(2-phenylethanol)propyl, 4-(2-phenylethanol)butyl,

5-(2-phenylethanol)pentyl and 6-(2-phenylethanol)hexyl.

Examples phenylcarbamoyl(lower)alkyl groups include phenylcarbamoyl the e group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, such as phenylcarbamoyl,

(1 or 2)phenylcarbamoyl, 3-(phenylcarbamoyl)propyl,

4-(phenylcarbamoyl)butyl, 5-(phenylcarbamoyl)pencil and

6-(phenylcarbamoyl)hexyl.

Examples of inlinegroup, optionally substituted in the phenyl ring by one or more lower alkoxygroup, each lower alkoxy-Deputy optionally substituted by one or more halogen atoms include:

inlinegroup, optionally substituted in the phenyl ring by one to three unbranched and/or branched C1-6alkoxygroup, each alkoxy-Deputy optionally substituted with one to three halogen atoms;

such as (2-, 3 - or 4-)chlormethiazole and

(2-, 3 - or 4-)triphtalocyaninine.

Examples of inlinegroup substituted in the amino group by one or more lower alkyl groups, and substituted in the phenyl ring by one or more halogen atoms include:

inlinegroup substituted in the amino group of one to three unbranched and/or branched C1-6alkyl groups, and substituted in the phenyl ring by one to three halogen atoms;

such asNmethyl-(2-, 3 - or 4-)chloraniline,

Nethyl-(2-, 3 - or 4-)chloraniline,

methyl-(2-, 3 - or 4-)bromoaniline,

Nmethyl-(2-, 3 - or 4-)fornerino,

Nethyl-(2-, 3 - or 4-)iodoaniline and

N-n-propyl-(2-, 3 - or 4-)chloraniline.

Examples of 5 - and 6-membered unsaturated heterocyclic rings formed by R8and R9while associating them with each other, together with the nitrogen atom to which they are attached, include (2 - or 3-)pyrrolin, 1,2-dihydropyridines, 2,3-dihydropyridines, 1,2,3,4-tetrahydropyridine, and 1,2,5,6-tetrahydropyridine.

Examples benzoline groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; phenyl groups; halogen atoms; ceanography; fenoxaprop; lower alkoxycarbonyl groups; parasailing groups and lower alkoxygroup, optionally substituted by one or more halogen atoms include:

benzoline group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; phenyl groups; halogen atoms; ceanography; fenoxaprop; above unbranched and branched C1-6alkoxycarbonyl groups; PI is asailing groups described above unbranched and branched C 1-6alkoxygroup, optionally substituted with one to three halogen atoms;

such as benzoyl, 4-methylbenzoyl, 3-methylbenzoyl,

2-methylbenzoyl, 4-tert-butylbenzoyl, 2,4-dimethylbenzoyl,

2,4,6-trimethylbenzoyl, 3-trifloromethyl,

4-trifloromethyl, 2-trifloromethyl, 4-phenylbenzyl,

4-chlorobenzoyl, 3-chlorobenzoyl, 2-chlorobenzoyl, 4-perbenzoic,

3-perbenzoic, 2-perbenzoic, 3-bromobenzoyl, 2-bromobenzoyl,

4-bromobenzyl, 3,4-dichlorobenzoyl, 2,3-dichlorobenzoyl,

2-chloro-4-perbenzoic, 2-methoxy-5-chlorobenzoyl, 4-methoxybenzoyl,

3-methoxybenzoyl, 2-methoxybenzoyl, 3,4-dimethoxybenzoyl,

3,4,5-trimethoxybenzoyl, 3-trifloromethyl,

4-trifloromethyl, 2-trifloromethyl,

3-cyanobenzoyl, 4-cyanobenzoyl, 2-cyanobenzoyl,

3-phenoxybenzoic, 2-phenoxybenzoic, 4-phenoxybenzoyl,

4-methoxycarbonylbenzyl, 3-ethoxycarbonylbutyl,

2-tert-butoxycarbonylmethyl and 4-(1-pyrazolyl)benzoyl.

Examples alkanoyl groups include unbranched and branched C1-10alcoholnye groups, such as, in addition to the above-described lower alkanoyl groups, heptanoyl, octanoyl, nonanoyl, decanoyl and 2-ethylhexanol.

Examples of phenyl(lower)alkanoyl groups, optionally substituted in the phenyl ring by one or more members selected isgroup, consisting of halogen atoms and lower alkyl groups include:

fenilalanina group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms and unbranched and branched C1-6alkyl groups;

such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl,

4-phenylbutyl, 5-phenylpentane, 6-phenylhexanoic,

2,2-dimethyl-3-phenylpropionyl, 2-methyl-3-phenylpropionyl,

2-(4-forfinal)acetyl, 3-(2,5-differenl)propionyl,

2-(2,4-differenl)propionyl, 4-(3,4-differenl)butyryl,

5-(3,5-differenl)pentanoyl, 6-(2,6-differenl)hexanoyl,

2-(2-chlorophenyl)acetyl, 3-(3-chlorophenyl)propionyl,

2-(4-chlorophenyl)propionyl, 4-(2,3-dichlorophenyl)propionyl,

5-(2,4-dichlorophenyl)pentanoyl, 6-(2,5-dichlorophenyl)hexanoyl,

2-(3,4-dichlorophenyl)acetyl, 3-(2,6-dichlorophenyl)propionyl,

2-(3-forfinal)propionyl, 4-(2-forfinal)butyryl,

5-(3-bromophenyl)pentanoyl, 6-(4-itfeel)hexanoyl,

2-(2-bromophenyl)acetyl, 3-(4-bromophenyl)propionyl,

2-(3,5-dichlorophenyl)propionyl, 4-(2,4,6-tryptophanyl)butyryl,

5-(3,4-differenl)pentanoyl, 6-(2-itfeel)hexanoyl,

2-(3-itfeel)acetyl, 3-(4-itfeel)propionyl,

2-(2,3-dibromophenyl)propionyl, 4-(2,4-diiodophenyl)Boo who iril,

2-(2,4,6-trichlorophenyl)acetyl, 2-(4-were)acetyl,

3-(2,5-dimetilfenil)propionyl, 2-(2,4-diethylphenyl)propionyl,

4-(3,4-di-npropylphenyl)butyryl, 2-(2-ethylphenyl)acetyl,

3-(3-npropylphenyl)propionyl, 2-(4-tert-butylphenyl)propionyl,

2-(2,4,6-trimetilfenil)acetyl,

2-(2,5-dichloro-4-were)acetyl,

2-(3-methyl-4-chlorophenyl)acetyl, 4-(2-nbutylphenyl)butyryl,

5-(3-npentylphenol)pentanol and 6-(4-nhexylphenyl)hexanoyl.

Examples of phenoxy(lower)alkanoyl groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

phenoxyalkanoic group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, optionally substituted in the phenyl ring by one to three halogen atoms;

such as, in addition to the above, phenoxy(lower)alkanoyl groups, 2-(4-chlorophenoxy)acetyl,

2-(4-pertenece)acetyl, 3-(2,5-divergence)propionyl, 2-(2,4-divergence)propionyl, 4-(3,4-divergence)butyryl, 5-(3,5-divergence)pentanoyl, 6-(2,6-divergence)hexanoyl, 2-(2-chlorophenoxy)acetyl, 3-(3-chlorophenoxy)propionyl, 2-(4-chlorphenoxy)propionyl, 4-(2,3-dichlorophenoxy)propionyl, 5-(2,4-dichlorphenoxy)pentanoyl, 6-(2,5-dichlorophenoxy)hexanoyl, 2-(3,4-dichlorophenoxy)acetyl, 3-(2,6-dichlorophenoxy)propionyl, 2-(3-FPO is phenoxy)propionyl, 4-(2-pertenece)butyryl, 5-(3-bromophenoxy)pentanoyl, 6-(4-iodinase)hexanoyl, 2-(2-bromophenoxy)acetyl, 3-(4-bromophenoxy)propionyl, 2-(3,5-dichlorophenoxy)propionyl, 4-(2,4,6-tryptophanate)butyryl, 5-(3,4-divergence)pentanoyl, 6-(2-iodinase)hexanoyl, 2-(3-iodinase)acetyl, 3-(4-iodinase)propionyl, 2-(2,3-dibromophenoxy)propionyl, 4-(2,4-deiodinase)butyryl and 2-(2,4,6-trichlorophenoxy)acetyl.

Examples of phenyl(lower)alkenylboronic groups include phenylacetylcarbinol group containing one to three double bonds, where alkanniny fragment is an unbranched or branched C2-6alkenylphenol group, such as strikeball (trivial name: cynnamoyl), 3-phenyl-2-propenylboronic, 4-phenyl-2-butylcarbamoyl, 4-phenyl-3-butylcarbamoyl, 5-phenyl-4-intercorporal, 5-phenyl-3-intercorporal, 6-phenyl-5-hexadecacarbonyl, 6-phenyl-4-hexadecacarbonyl, 6-phenyl-3-hexadecacarbonyl, 4-phenyl-1,3-butadienerubber and 6-phenyl-1,3,5-extrauniversal.

Examples pyridylcarbonyl groups, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms include:

pyridylcarbonyl group, not necessarily nesennye in the pyridine ring with one to three members, selected from the group consisting of halogen atoms and the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms;

such as (2-, 3 - or 4-)pyridylcarbonyl,

2-chloro-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,6-dichloro-(3-, 4 - or 5-)pyridylcarbonyl,

2,3-dichloro-(4-, 5 -, or 6-)pyridylcarbonyl,

2-trifluoromethyl-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2-bromo-(3-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,6-debtor-(3-, 4 - or 5-)pyridylcarbonyl,

4-methyl-(2-, 3-, 5 -, or 6-)pyridylcarbonyl,

3-chloro-(2-, 4-, 5 -, or 6-)pyridylcarbonyl,

2,5-dibromo-(3-, 4 - or 5-)pyridylcarbonyl,

2-ethyl-4-chloro-(3-, 5 -, or 6-)pyridylcarbonyl,

2,4,6-Cryptor-(3 - or 5-)pyridylcarbonyl,

2,4-dimethyl-(3-, 5 -, or 6-)pyridylcarbonyl,

2,4,6-trimethyl-(3 - or 5-)pyridylcarbonyl and

2-methyl-4-chloro-(3-, 5 -, or 6-)pyridylcarbonyl.

Examples piperidinylcarbonyl groups, optionally substituted in piperidinium ring by one or more lower alkanolamine groups include piperidinylcarbonyl group, optionally substituted in piperidinium ring one to three unbranched and/or branched C1-6alkanolamine groups, such as (2-, 3 - or 4-)piperidinylcarbonyl,

1-acetyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-npropanol-(2-, 3 - or 4-)piperidinylcarbonyl,

1-isopropanol-(2-, 3 - or 4-)PI is originalarbeit,

1-nbutyryl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-npentanoyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1-nhexanoyl-(2-, 3 - or 4-)piperidinylcarbonyl,

1,2-diacetyl-(3-, 4-, 5 -, or 6-)piperidinylcarbonyl,

1,2,3-triacetyl-(4-, 5 -, or 6-)piperidinylcarbonyl,

2-acetyl-(1-, 3-, 4-, 5 -, or 6-)piperidinylcarbonyl,

3-propanol-(1-, 2-, 4-, 5 -, or 6-)piperidinylcarbonyl and

2-formyl-4-propanol-(1-, 3-, 5 -, or 6-)piperidinylcarbonyl.

Examples tetrahydroprotoberberine groups include 2-tetrahydropyranyl, 3-tetrahydropyranyl and 4-tetrahydropyranyl.

Examples benzothiadiazole groups, optionally substituted in benzothiophene ring by one or more halogen atoms include benzotriazole group, optionally substituted in benzothiophene ring with one to three halogen atoms,

such as (2-, 3-, 4-, 5-, 6 - or 7-)benzothiazolinone,

[3-chloro-(2-, 4-, 5-, 6 - or 7-)benzothieno]carbonyl,

[4-bromo-(2-, 3-, 5-, 6 - or 7-)benzothieno]carbonyl,

[5-fluoro-(2-, 3-, 4-, 6 - or 7-)benzothieno]carbonyl,

[6-iodine-(2-, 3-, 4-, 5 -, or 7-)benzothieno]carbonyl,

[7-chloro-(2-, 3-, 4-, 5 -, or 6-)benzothieno]carbonyl,

[2-chloro-(3-, 4-, 5-, 6 - or 7-)benzothieno]carbonyl,

[2,3-dichloro-(4-, 5-, 6 - or 7-)benzothieno]carbonyl and

[3,4,6-trichloro-(2-, 5 -, or 7-)benzothieno]carbonyl.

Examples of pyridyl(lower)alkyl groups, neo is Astelin substituted in the pyridine ring by one or more members, selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms include:

pyridylamine group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the pyridine ring with one to three members selected from the group consisting of halogen atoms and the above-described non-branched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms;

such as (2-, 3 - or 4-)pyridylmethyl,

2-[(2-, 3 - or 4-)pyridyl]ethyl, 1-[(2-, 3 - or 4-)pyridyl]ethyl,

3-[(2-, 3 - or 4-)pyridyl]propyl,

4-[(2-, 3 - or 4-)pyridyl]butyl,

1,1-dimethyl-2-[(2-, 3 - or 4-)pyridyl]ethyl,

5-[(2-, 3 - or 4-)pyridyl]pentyl,

6-[(2-, 3 - or 4-)pyridyl]hexyl,

1-[(2-, 3 - or 4-)pyridyl]isopropyl,

2-methyl-3-[(2-, 3 - or 4-)pyridyl]propyl,

[2-chloro-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2,3-dichloro-(4-, 5 -, or 6-)pyridyl]methyl,

[2-bromo-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2,4,6-Cryptor-(3-, 5 -, or 6-)pyridyl]methyl,

[2-trifluoromethyl-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-methyl-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2-ethyl-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

2-[2-npropyl-(3-, 4-, 5 -, or 6-)pyridyl]ethyl,

3-[2-nbutyl-(3-, 4-, 5 -, or 6-)pyridyl]propyl,

4-[2-npentyl-(3-, 4, 5 - or 6-)pyridyl]butyl,

5-[2-nhexyl-(3-, 4-, 5 -, or 6-)pyridyl]pentyl,

6-[2-isopropyl-(3-, 4-, 5 -, or 6-)pyridyl]hexyl,

[2-tert-butyl-(3-, 4-, 5 -, or 6-)pyridyl]methyl,

[2,4-dimethyl-(3-, 5 -, or 6-)pyridyl]methyl,

[2,4,6-trimethyl-(3 - or 5-)pyridyl]methyl,

[2,4-DATEFORMAT-(3-, 5 -, or 6-)pyridyl]methyl,

2-(2,4-bistritei)-(3-, 5 -, or 6-)pyridyl)ethyl and

3-[2-methyl-6-chloro-(3-, 4 - or 5-)pyridyl]propyl.

Examples thienyl(lower)alkyl group, optionally substituted in the thiophene ring with one or more halogen atoms include:

taylorkillian group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the thiophene ring with one to three halogen atoms;

such as [(2 - or 3-)thienyl]methyl, 2-[(2 - or 3-)thienyl]ethyl,

1-[(2 - or 3-)thienyl]ethyl, 3-[(2 - or 3-)thienyl]propyl,

4-[(2 - or 3-)thienyl]butyl, 5-[(2 - or 3-)thienyl]pentyl,

6-[(2 - or 3-)thienyl]hexyl,

1,1-dimethyl-2-[(2 - or 3-)thienyl]ethyl,

2-methyl-3-[(2 - or 3-)thienyl]propyl,

[2-chloro-(3-, 4 - or 5-)thienyl]methyl,

[4-bromo-(2-, 3 - or 5-)thienyl]methyl,

[5-fluoro-(2-, 3 - or 4-)thienyl]methyl,

[3-iodine-(2-, 4 - or 5-)thienyl]methyl,

[2,3-dichloro-(4 - or 5-)thienyl]methyl,

(2,4,5-trichloro-3-thienyl)methyl,

2-[2-fluoro-(3-, 4 - or 5-)thienyl]ethyl,

1-[4-iodine-(2-, 3 - or 5-)thienyl]ethyl,

3-[3-chloro-(2-, 4 - or 5-)thienyl]propyl,

4[4,5-dichloro-(2 - or 3-)thienyl]butyl,

5-(2,4,5-trichloro-3-thienyl)pentyl and

6-[2-chloro-(3-, 4 - or 5-)thienyl]hexyl.

Examples of amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups include:

amino group, optionally substituted by one or two members selected from the group consisting of unbranched and branched C1-6alkyl groups and unbranched and branched C1-6alkanoyl groups;

such as amino, formylamino, acetylamino, propionamido, bucillamine, isobutylamino, pentanediamine,tert-BUTYLCARBAMATE, hexanamine,N,Ndiatsetilamino,Nacetyl-Npropionamido, methylamino, ethylamino,npropylamino, isopropylamino,nbutylamino,npentylamine,nhexylamino, dimethylamino, 3-diethylamino, diisopropylamino,Nethyl-N-n-propylamino,Nmethyl-N-n-hexylamino,Nmethyl-Nacetylamino andNethyl-Nacetylamino.

Examples of phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, optionally substituted by one or more halogen atoms; ceanography; lower alkyl groups optionally substituted by one or more of at the Mami halogen; amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups; halogen atoms; lower alkoxycarbonyl groups; lower alkanoyloxy; lower alkylsulfonyl groups; lower alkylthio and pyrrolidinyl groups include:

mono - and diphenylethylene group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of the above-described non-branched and branched C1-6alkoxygroup, optionally substituted with one to three halogen atoms; ceanography; above unbranched and branched C1-6alkyl groups, optionally substituted with one to three halogen atoms; the above-described amino groups, optionally substituted by one or two members selected from the group consisting of unbranched and branched C1-6alkyl groups and unbranched and branched C1-6alkanoyl groups; halogen atoms; the above-described non-branched and branched C1-6alkoxycarbonyl groups; the above-described non-branched and branched C2-6alkanoyloxy; above unbranched and branched C 1-6alkylsulfonyl groups; the above-described non-branched and branched C1-6alkylthio and pyrrolidinyl groups;

such as benzyl, 1-phenethyl, 2-phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 4-fenilpentil, 6-phenylhexa, 2-methyl-3-phenylpropyl, 1,1-dimethyl-2-phenylethyl, 1,1-diphenylmethyl, 2,2-diphenylether, 3,3-diphenylpropyl,

1,2-diphenylether, 4-Chlorobenzyl, 2-Chlorobenzyl, 3-Chlorobenzyl, 3-tormentil, 4-tormentil, 2-tormentil, 4-bromobenzyl, 3-bromobenzyl, 2-bromobenzyl, 1-(2-chlorophenyl)ethyl, 2,3-dichlorobenzyl, 2,4,6-triptorelin, 2-trifloromethyl, 3-trifloromethyl, 4-trifloromethyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 4-nbutylbenzoyl, 2,4-dimethylbenzyl, 2,4,6-trimethylbenzyl, 2-phenylbenzyl, 4-phenylbenzyl, 2,4-diphenylmethyl, 2,4,6-triphenylbenzene, 2-cryptomaterial, 3-cryptomaterial, 4-cryptomaterial, 4-deformational, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 4-nbutoxymethyl, 4-tert-butoxymethyl, 1-(3-methoxyphenyl)ethyl, 1-(4-methoxyphenyl)ethyl, 1-(2-methoxyphenyl)ethyl, 3,4-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 4-methoxycarbonylbenzyl, 3-ethoxycarbonylphenyl, 2-npropoxycarbonyl, 2,4-dimethoxybenzyl, 2,4,6-trimethoxybenzyl, 1-(4-nbutoxyphenyl)ethyl, 4-tert-butoxycarbonylmethyl, 4-methylthio ensil, 3-methylthiophenyl, 2-methylthioethyl, 4-ethylthiomethyl, 2,4-dimethylthiophenol, 2,4,6-trimethylstyrene, 4-methylsulfonylbenzoyl, 3-methylsulfonylbenzoyl, 2-methylsulfonylbenzoyl, 3,4-dimethylsulphamoyl, 3,4,5-trimethylbenzyl, 4-methoxy-3-Chlorobenzyl, 4-(Nacetylamino)benzyl, 4-(N,N-diethylamino)benzyl, 4-(N,N-dimethylamino)benzyl, 4-(Nmethylamino)benzyl, 3-aminobenzyl, 2-aminobenzyl, 4-aminobenzyl, 4-acetyloxybenzoic,

2,3-diaminobenzoic, 3,4,5-triaminobenzene, 4-methyl-3-tormentil,

4-cyanobenzyl, 3-cyanobenzyl, 2-cyanobenzyl,

4-(1-pyrrolidinyl)benzyl, 4-methoxy-2-Chlorobenzyl and

3-chloro-5-methylbenzyl.

Examples thiazolyl(lower)alkyl groups include tutorialnya group, where the alkyl fragment is an unbranched or branched C1-6alkyl group,

such as [(2-, 4 - or 5-)thiazolyl]methyl,

2-[(2-, 4 - or 5-)thiazolyl]ethyl,

1-[(2-, 4 - or 5-)thiazolyl]ethyl,

3-[(2-, 4 - or 5-)thiazolyl]propyl,

4-[(2-, 4 - or 5-)thiazolyl]butyl,

5-[(2-, 4 - or 5-)thiazolyl]pentyl,

6-[(2-, 4 - or 5-)thiazolyl]hexyl,

1,1-dimethyl-2-[(2-, 4 - or 5-)thiazolyl]ethyl and

[2-methyl-3-[(2-, 4 - or 5-)thiazolyl]propyl.

Examples imidazolyl(lower)alkyl group, optionally substituted in the imidazole ring by one or more lower alkyl groups include:

imidazolylalkyl group, where alkyl the first fragment is an unbranched or branched C 1-6alkyl group, optionally substituted in the imidazole ring with one to three above unbranched and branched C1-6alkyl groups;

such as [(1-, 2-, 4 - or 5-)imidazolyl]methyl,

2-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

1-[(1-, 2-, 4 - or 5-)imidazolyl]ethyl,

3-[(1-, 2-, 4 - or 5-)imidazolyl]propyl,

4-[(1-, 2-, 4 - or 5-)imidazolyl]butyl,

1,1-dimethyl-2-[(1-, 2-, 4 -, or 5)imidazolyl]ethyl,

5-[(1-, 2-, 4 - or 5-)imidazolyl]pentyl,

6-[(1-, 2-, 4 - or 5-)imidazolyl]hexyl,

1-[(1-, 2-, 4 - or 5-)imidazolyl]isopropyl,

2-methyl-3-[(1-, 2-, 4 - or 5-)imidazolyl]propyl,

[1-methyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-ethyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-npropyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-nbutyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-npentyl-(2-, 4 - or 5-)imidazolyl]methyl,

[1-nhexyl-(2-, 4 - or 5-)imidazolyl]methyl,

2-[2-methyl-(1-, 4 - or 5-)imidazolyl]ethyl,

1-[1-ethyl-(2-, 4 - or 5-)imidazolyl]ethyl,

3-[1-ethyl-(2-, 4 - or 5-)imidazolyl]methyl,

4-[1-npropyl-(2-, 4 - or 5-imidazolyl]butyl,

5-[1-nbutyl-(2-, 4 - or 5-)imidazolyl]pentyl,

6-[1-npentyl-(2-, 4 - or 5-)imidazolyl]hexyl,

[1,2-dimethyl-(4 - or 5-)imidazolyl]methyl and

(1,2,4-trimethyl-5-imidazolyl)methyl.

Examples pyrrolyl(lower)alkyl group, optionally substituted in the pyrrole ring by one or more lower alkyl group and, include:

paralellnye group, where the alkyl fragment is an unbranched or branched C1-6alkyl group, optionally substituted in the pyrrole ring one to three above unbranched and branched C1-6alkyl groups;

such as [(1-, 2 - or 3-)pyrrolyl]methyl,

2-[(1-, 2 - or 3-)pyrrolyl]ethyl,

1-[(1-, 2 - or 3-)pyrrolyl]ethyl,

3-[(1-, 2 - or 3-)pyrrolyl]propyl,

4-[(1-, 2 - or 3-)pyrrolyl]butyl,

1,1-dimethyl-2-[(1-, 2 - or 3-)pyrrolyl]ethyl,

5-[(1-, 2 - or 3-)pyrrolyl]pentyl,

6-[(1-, 2 - or 3-)pyrrolyl]hexyl,

1-[(1-, 2 - or 3-)pyrrolyl]isopropyl,

2-methyl-3-[(1-, 2 - or 3-)pyrrolyl]propyl,

[1-methyl-(2 - or 3-)pyrrolyl]methyl,

[1-ethyl-(2 - or 3-)pyrrolyl]methyl,

[1-npropyl-(2 - or 3-)pyrrolyl]methyl,

[1-nbutyl-(2 - or 3-)pyrrolyl]methyl,

[1-npentyl-(2 - or 3-)pyrrolyl]methyl,

[1-nhexyl-(2 - or 3-)pyrrolyl]methyl,

2-[2-methyl-(1-, 3-, 4 - or 5-)pyrrolyl]ethyl,

1-[1-ethyl-(2 - or 3-)pyrrolyl]ethyl,

3-[1-ethyl-(2 - or 3-)pyrrolyl]methyl,

4-[1-npropyl-(2 - or 3-)pyrrolyl]butyl,

5-[1-nbutyl-(2 - or 3-)pyrrolyl]pentyl,

6-[1-npentyl-(2 - or 3-)pyrrolyl]hexyl,

[1,2-dimethyl-(3-, 4 - or 5-)pyrrolyl]methyl and

[1,2,4-trimethyl-(3 - or 5-)pyrrolyl]methyl.

Examples of lower alkylthio(lower)alkyl groups include alkylthiomethyl group, where each of dualling fragments represents an unbranched or branched C 1-6alkyl group, such as methylthiomethyl, 2-methylthioethyl, 1-ethylthioethyl, 2-ethylthioethyl, 3-nbutylthioethyl, 4-npropylthiouracil, 1,1-dimethyl-2-npentultimate, 5-nhexylthiophene, 6-methylthioethyl, 1-ethylthioethyl and 2-methyl-3-metaltipped.

Examples phenoxycarbonyl groups, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxygroup include:

phenoxycarbonyl group, optionally substituted in the phenyl ring by one to three members selected from the group consisting of halogen atoms described above unbranched and branched C1-6the alkyl groups described above unbranched and branched C1-6alkoxygroup;

such as phenoxycarbonyl, 4-chlorophenoxyacetic,

3-chlorphenoxamine, 2-chlorphenoxamine,

3,4-dichlorophenoxyacetic, 2,4,6-trichlorophenoxyacetic,

4-pertenecieron, 3-pertenecieron,

2-pertenecieron, 2,4-divergenceerror,

3,4,5-cryptorhynchinae, 4-bromophenanthrene, 2-chloro-4-methoxyphenethyl, 3-fluoro-5-methylphenoxyacetic, 4-methoxyphenethyl, 3-methoxyphenethyl, 2-methoxyprogesterone, 3,4-dimethoxyphenethylamine, 2,4,5-trimethoxyphenethylamine,4-methylphenoxyacetic, 3-methylphenoxyacetic, 2-methylphenoxyacetic,

2.5-dimethylphenylcarbinol and 2,3,4-trimethylhexanoyl.

Examples of phenyl(lower)alkoxycarbonyl groups, optionally substituted in the phenyl ring by one or more halogen atoms include:

generalquartiermeister group, where the alkoxy fragment is an unbranched or branched C1-6alkoxygroup, optionally substituted in the phenyl ring by one to three halogen atoms;

such as benzyloxycarbonyl, 2-fenilalaninammonii,

1-fenilalaninammonii, 3-phenylpropionyl,

4-privateserver, 5-phenylmethylsulphonyl,

6-vanillacracker, 1,1-dimethyl-2-fenilalaninammonii,

2-methyl-3-phenylpropionyl, 2-chlorobenzenesulfonyl,

3-chlorobenzylidene, 2-chlorobenzenesulfonyl,

3,4-dichlorobenzenesulfonyl, 2,4,6-trichlorophenoxypropionic,

4-forantimicrobial, 3-forantimicrobial,

2-forantimicrobial, 2,4-differentlocations,

3,4,5-triftoratsetilatsetonom, 4-bromobenzyloxycarbonyl,

4-nitrobenzeneboronic and 3-nitrobenzanthrone.

Examples hinoklidilkarbinola groups include 2-hinoklidilkarbinola, 5-hinoklidilkarbinola and 6-hinoklidilkarbinola.

Examples of phenyl(lower)alkanoyl groups include fenilalanina group, where alcoholly fragment is an unbranched or branched C2-6alkanoyloxy group, such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyl, 5-phenylpentane, 6-phenylhexanoic, 2,2-dimethyl-2-phenylpropionyl and 2-methyl-3-phenylpropionyl.

Compounds of the present invention can be obtained, for example, schemes 1-16 reactions. All of the original substance and the target compounds are shown in schemes 1 to 16, can be in the form of suitable salts. Examples of such salts are salts described below for barbastelles the compounds of formula (1).

Scheme 1 reactions

where R1, R2, R3, R4, R5X and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, R15represents a hydrogen atom or a lower alkyl group and A4represents a direct bond or lower alkylenes group, provided that the total number of carbon atoms of the group, replacing carbothermally skeleton, ie-CH(R15)-A4-less than 6.

The interaction of the compound (2) with compound (3) is carried out in a suitable solvent in the presence of a basic compound or acid.

The examples used in this reaction solvents are aromatic coal is torodi, such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol,tert-butanol and ethylene glycol, aliphatic acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide,N,N-dimethylformamide, hexamethylphosphoric triamide, mixed solvents of these solvents, etc.

Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholate such as sodium methylate, sodium ethylate andn-piperonyl sodium, piperidine, pyridine, imidazole,N-ethyldiethanolamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline,N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonan-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO) and the like organic bases and mixtures thereof.

Examples of acids are what I organic acids, such as p-toluensulfonate acid and like sulfonic acid and acetic acid, triperoxonane acid, trichloroacetic acid and like aliphatic acid; inorganic acids such as hydrochloric acid, sulfuric acid, Hydrobromic acid and phosphoric acid, and mixtures thereof.

In the present invention, the basic compound and the acid can be used in combination.

The primary connection or acid is used usually in a catalytic amount, preferably in an amount of about 0.01 to 1 mol per mol of compound (2).

The compound (3) is used usually in an amount of at least 1 mole, preferably about 1-2 mol per mol of compound (2).

The reaction is usually carried out at a temperature in the range of from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete in about 0.5 to 20 hours.

The reaction of obtaining compound (1b) from the compound (1a) is carried out, for example, either without solvent or in a suitable solvent in the presence of a reducing agent.

The examples used in this reaction solvents are water, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, acetonitrile, aliphatic acid, such as m Ravina acid and acetic acid, ethers, such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride,N,N-dimethylformamide, mixtures of these solvents, etc.

Examples of reducing agents are mixtures of silicon dioxide and pyridine derivatives, such as diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate; borohydride sodium, borohydride lithium, cyanoborohydride sodium, triacetoxyborohydride sodium, sociallyengaged and similar hydride reducing agents; mixtures of these hydride reducing agents; palladium black, palladium on carbon, platinum oxide, platinum black, Raney Nickel and the like, the reducing agent for the catalytic hydrogenation; and so on

When used as a reductant mixture of a derivative of pyridine and silicon dioxide suitable reaction temperature ranges usually from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete in about 0.5 to 50 hours. A derivative of pyridine is used usually in an amount of at least 1 mol, preferably 1-3 mol per mol of compound (1a). Silicon dioxide is used usually in Koli is este at least 1 mol, preferably 1-10 mol per mol of compound (1a).

When using a hydride reducing agent suitable reaction temperature ranges usually from about -80 to about 100°C, preferably from about -80 to about 70°C. the Reaction usually ends at a time in the range of from about 30 minutes to about 60 hours. Hydride reducing agent is used usually in an amount of from about 0.1 to about 20 mol, preferably from about 0.1 to about 6 mol per mol of compound (1b). In particular, when a hydride reducing agent used sociallyengaged, preferably diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme and the like ethers, benzene, toluene, xylene and like aromatic hydrocarbons as solvents. In the reaction system of the reaction in the presence of pyridine, trimethylamine, triethylamine,N-ethyldiethanolamine or similar amine; sodium hydroxide or similar inorganic bases and/or dimethylglyoxime, 2,2'-bipyridyl, 1,10-phenanthroline or similar ligand can be added chloride cobalt(II)chloride cobalt(III), cobalt acetate(II) or a similar compound of cobalt.

When using a reducing agent for the catalytic hydrogenation reaction is usually carried out at a temperature in the range of from about -30 d is about 100°C, preferably from about 0 to about 100°C, in an atmosphere of hydrogen at a pressure of from about atmospheric pressure to about 20 ATM, preferably about atmospheric pressure to about 10 ATM, or in the presence of formic acid, ammonitrate cyclohexane, hydrazine hydrate or similar donor of hydrogen. The reaction is usually complete after about 1-12 hours. The reducing agent for the catalytic hydrogenation is used usually in an amount of about 0.01 to 5 times, preferably about 1-3 times the mass of the compound (1a).

Scheme 2 reactions

where R1, R2, R4, R5and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R16represents a lower alkyl group.

The compound (1c) is produced by interaction of the compound (4) and compound (5) in a suitable solvent in the presence of a basic compound, followed by treatment with an acid. Specified treatment with an acid hereinafter referred to as “acid treatment”.

The examples used in this reaction solvents are water, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme and diglyme, halogenated hydrocarbons, so the e as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, aliphatic acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide,N,N-dimethylformamide, hexamethylphosphoric triamide, mixed solvents of these solvents, etc.

Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholate such as sodium methylate, sodium ethylate, n-piperonyl sodium, sodium acetate, piperidine, pyridine, imidazole,N-ethyldiethanolamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline,N-methylmorpholine, DBN, DBU, DABCO, other organic bases and mixtures of these bases.

The primary connection is used usually in an amount of at least about 1 mol, preferably from about 1 to about 3 mol, per mol of compound (4).

The compound (5) is used usually in an amount of at least about 1 mol, preferably from prima is but 1 to about 2 mol, per mole of the compound (4).

The reaction is usually carried out at a temperature in the range of from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete in about 0.5 to 10 hours.

Examples of acids used in the acid treatment of the reaction product are inorganic acids such as hydrochloric acid, sulfuric acid, Hydrobromic acid and the like. These acid is used usually in large excess relative to the processed product of the reaction.

Examples of solvents used in the acid treatment, include solvents used in the above-described engagement of the compound (4) with compound (5).

The acid treatment is carried out usually at a temperature from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Acid treatment is usually complete in about 0.5 to 30 hours.

The interaction of the compound (4) with compound (6) is carried out in similar conditions, the interaction of the compound (4) with compound (5).

Scheme 3 reactions

where R1, R2, R4, R5, X, A, and the relationship between the clauses 3 and 4 carbothermally are such as defined above; X1represents a halogen atom and R3arepresents a group other than hydrogen atom as defined above in connection with R3.

The interaction of the compound (1e) and the compound (7) is carried out in a suitable inert solvent in the presence of a basic compound.

Examples of the inert solvent used in this reaction are aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, aliphatic acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethylsulfoxide,N,N-dimethylformamide, hexamethylphosphoric triamide, mixed solvents of these solvents, etc.

Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, sodium hydride, the hydride feces is I, potassium, sodium, sodium amide, metal alcoholate such as sodium methylate, sodium ethylate, n-piperonyl sodium tert-piperonyl sodium tert-piperonyl potassium, pyridine, imidazole,N-ethyldiethanolamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline,N-methylmorpholine, DBN, DBU, DABCO, other organic bases and mixtures of these bases.

The primary connection is used usually in an amount of at least 1 mol, preferably 1-10 mol, per mol of compound (1e).

Compound (7) is used usually in an amount of at least 1 mol, preferably 1-10 mol, per mol of compound (1e).

The reaction is usually carried out at a temperature in the range of from about 0 to about 200°C, preferably from 0 to about 150°C. the Reaction usually ends at a time in the range of from about 5 minutes to about 80 hours.

In the reaction system, the reaction can be entered sodium iodide, potassium iodide or the like alkali metal halide.

When the interaction of the compound (1e) with compound (7) is used as a compound (1e), where X represents sulfur, sometimes produces compound represented by the formula:

where R1, R2, R4, R5, R3a, And A relationship between positions 3 and 4 barbastelle skeleton are as defined above. This soy is inania can be easily separated from the reaction mixture.

Scheme 4 reaction

where R1, R2, R4, R5, A4, R15, R16X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R17represents a lower alkyl group.

Obtaining compound (9) from compound (8) carry out the hydrolysis reaction of the compound (8).

This hydrolysis reaction is conducted, for example, in a suitable solvent or without solvent in the presence of acid or base.

Examples of the used solvents are water, lower alcohols such as methanol, ethanol, isopropanol andtert-butanol, ketones, such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme, aliphatic acids such as acetic acid and formic acid, esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloroethane, dichloromethane, carbon tetrachloride, dimethyl sulfoxide,N,N-dimethylformamide, hexamethylphosphoric triamide, mixed solvents of these solvents, etc.

Examples of acids are mineral acids such as hydrochloric acid, sulfuric acid and Hydrobromic acid, and organic acids such as formic what I acid, acetic acid, triperoxonane acid, p-toluensulfonate acid and like sulfonic acid. These acids may be used individually or in combination of two or more such acids.

Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate; metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and lithium hydroxide; etc. These basic compounds may be used individually or in combination of two or more such compounds.

The hydrolysis reaction is expedient to carry out usually at about 0 to 200°C, preferably at about 0-150°C. the Reaction usually ends at a time in the range of from about 10 minutes to about 30 hours.

The compound (1g) can be obtained by interaction of the compound (8) with compound (5) in a suitable solvent in the presence or in the absence of a basic compound and then acid treatment of the reaction product. Alternatively, the compound (1g) can be obtained by interaction of the compound (9) with compound (5) in a suitable solvent in the presence or in the absence of a basic compound and then acid treatment of the reaction product.

Examples of solvents used in the interaction of the compound (8) is connected to the eat (5) and the interaction of the compound (9) with compound (5), include in addition to sulfolane solvents used in the interaction of the compound (4) with compound (5)shown in scheme 2, above.

Examples of basic compounds include solvents used in the interaction of the compound (4) with compound (5)shown in scheme 2, above.

The primary connection is used usually in an amount of at least 1 mole, preferably 1-2 moles, per mole of the compound (5). Compound (8) and compound (9) is used in amounts of generally at least 1 mol, preferably 1-5 mol, per mol of compound (5).

The reaction is usually carried out in the range of from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete in about 0.5 to 10 hours.

Subsequent acid treatment is carried out under the same conditions as described above regarding the “acid treatment And diagram 2.

Scheme 5 reactions

where R1, R2, R3, R4, R5, X, A, X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R1arepresents a group other than a hydrogen atom, a particular in connection with R1.

The interaction of the compound (1h) with the the group of (10) is carried out in the same conditions, as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Scheme 6 reaction

where R2, R3, R4, R5, X, A, R8, R9, A1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.

For the interactions of the compound (1j) with compound (11) apply a variety of reaction conditions selected for the normal formation of the amide bond, such in particular as (a) a method of obtaining a mixed anhydride of the acid, where the carboxylic acid (1j) is subjected to interaction with alkylphenolethoxylates with the formation of the mixed anhydride of the acid and the resulting anhydride is subjected to interaction with amine (11), (b) the method of obtaining the activated complex ether, where the carboxylic acid (1j) activate activated ester such as phenyl ester,p-nitrophenyloctyl ether,N-hydroxysuccinimidyl ether, 1-hydroxybenzotriazole ether, etc. or an activated amide benzoxazolyl-2-tion and then subjected to interaction with amine (11), (c) a method of obtaining a carbodiimide, where the carboxylic acid (1j) and amine (11) is subjected to the condensation reaction in the presence of activating agents, such as dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl is)-3-ethylcarbodiimide (WSC), carbonyldiimidazole or the like, (d) other methods, for example, where the carboxylic acid (1j) is converted into a carboxylic acid anhydride using a dehydrating agent, such as acetic anhydride, and subjecting the obtained carboxylic acid anhydride interaction with amine (11); ester carboxylic acid (1j), formed using the amine (11) at high temperature and high pressure; gelegenheid carboxylic acid (1j), i.e. a carboxylic acid chloride, is subjected to the interaction with the amine (11) and similar methods.

The mixed acid anhydride for use in the above method of obtaining the mixed anhydride can be obtained in the usual reaction of Schotten's-Bauman, and the reaction product is usually use to interact with amine (11) to obtain the desired compounds of formula (1k) without isolation from the reaction mixture.

The above-described reaction of the Schotten's-Bauman usually carried out in the presence of a basic compound.

These basic compounds include any of the traditional bases for use in the reactions of Schotten's-Bauman, such as triethylamine, trimethylamine, pyridine, dimethylaniline,N-ethyldiethanolamine, dimethylaminopyridine,N-methylmorpholine, DBN, DBU, DABCO and the like organic bases, and carbonates such as sodium carbonate, potassium carbonate, hydrocarbon is tons of sodium and potassium bicarbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, potassium hydride, sodium hydride, potassium, sodium, sodium amide, metal alcoholate such as sodium methylate and sodium ethylate and the like inorganic bases. These basic compounds are used alone or in combination of two or more such compounds. The reaction is usually carried out at a temperature in the range of from about -20 to about 100°C, preferably from about 0 to about 50°C. the reaction Time is from about 5 minutes to about 10 hours, preferably from about 5 minutes to about 2 hours.

The interaction of the obtained mixed acid anhydride with amine (11) is usually carried out at a temperature in the range of from about -20 to about 150°C, preferably from about 10 to about 50°C. the reaction Time is from about 5 minutes to about 10 hours, preferably from about 5 minutes to about 5 hours.

Getting mixed anhydride of the acid is usually carried out in a solvent. Examples of solvents are solvents which are usually used in the methods of obtaining the mixed anhydrides of the acid. Specific examples are chloroform, dichloromethane, dichloroethane, carbon tetrachloride and the like halogenated hydrocarbons; benzene, toluene, xylene and the like fragrance is ical hydrocarbons; diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane and like ethers; methyl acetate, ethyl acetate, isopropylacetate and the like esters;N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide and the like aprotic polar solvents; mixtures of these solvents; and so on

Examples of alkylphenolethoxylates used in the method of obtaining a mixed anhydride, are methylchloroform, methylbromide, ethylchloride, ethylbromide, isobutylacetate etc.

In a method of producing a mixed acid anhydride of carboxylic acid (1j), alkylcarboxylic and amine (11) is preferably used in equimolar relative to each other quantities. However, alkylcarboxylic and Amin (11) can be used each in an amount of from about 1 to about 1.5 mol per mol of carboxylic acid (1j).

Method (c), where the condensation reaction carried out in the presence of the above-described activating substances is carried out in a suitable solvent in the presence or in the absence of a basic compound. Examples of the solvents and basic compounds used in this method are solvents and bases, which are used in the method, where the acid chloride of the carboxylic acid is subjected to interaction with the amine (1b), as described neither the e in connection with the methods (d). Activating substance use usually in the amount of at least 1 mol, preferably 1-5 mol, per mole of the compound (1j). When the activating substance use WSC is advisable to promote the reaction by introduction of 1-hydroxybenzotriazole in the reaction system. The reaction is usually carried out at a temperature in the range of from about -20 to about 180°C, preferably from about 0 to about 150°C. the Reaction is usually complete within from about 5 minutes to about 90 hours.

If method (d) select the way where the acid chloride of the carboxylic acid is subjected to interaction with amine (11), this reaction is carried out in the presence of a basic compound in a suitable solvent. Examples of basic compounds include a variety of known compounds, such as described above in connection with the reaction of the Schotten's-Bauman. Examples of solvents include, in addition to the solvents used in the above method of obtaining a mixed acid anhydride, methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, methylcellosolve and similar alcohols, acetonitrile, pyridine, acetone, water, etc. the Ratio of acid chloride of carboxylic acid to amine (11) is not limited and may be selected from a wide range. It usually is such that the mol glaring drid amine is used in amounts of at least about 1 mol, preferably about 1-5 mol. The reaction is usually carried out at a temperature in the range of from about -20 to about 180°C, preferably from about 0 to about 150°C. the Reaction is usually complete within from about 5 minutes to about 30 hours.

In addition, the reaction of the formation of amide linkages, shown in scheme 6, can be carried out by the interaction of the carboxylic acid (1j) and amine (11) in the presence of a condensing agent, representing a compound of phosphorus, such as triphenylphosphine, diphenylphosphinite, floridat phenyl-N-phenylphosphonite, diethylphosphate, diethylthiophosphate, diphenylacetate, bis(2-oxo-3-oxazolidinyl)fatfingered etc. These condensing agents can be used individually or in combination of two or more such agents.

The reaction is usually carried out at a temperature in the range of from about -20 to about 150°C, preferably from about 0 to about 100°C, using the solvent and the basic compound, which is also used in the above method, in which the interaction of the acid chloride of carboxylic acid and amine (11). The reaction is normally complete within from about 5 minutes to about 30 hours. The condensing agent and the amine (11) are used each in an amount of at least about 1 mol, preferably when is Erno 1-2 mol, per mole of carboxylic acid (1j).

Scheme 7 reaction

where R2, R3, R4, R5, X, A, and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, R1brepresents a group defined above (1-9) in connection with R1and R1crepresents a group defined above (1-8) in connection with R1.

The reaction of obtaining the compound (1m) from the compound (1l) carried out under the conditions described in connection with the reaction of obtaining compound (9) from compound (8)shown above in scheme 4.

The compound (1l) can be obtained from compound (1m) interaction of the compound (1m) with the compound represented by the formula

R23OH (50),

where R23represents a lower alkyl group.

For this reaction the applicable terms, is usually selected for esterification reactions. For example, it can be carried out in the presence of hydrochloric acid, sulfuric acid or similar mineral acid or thionyl chloride, phosphorus oxychloride, pentachloride phosphorus, trichloride phosphorus or similar halogenation agent. The compound (50) is used in large excess relative to the compound (1m). The reaction is expedient to carry out usually at about 0-150°C, preferably about 50-100°C. the Reaction is usually ending is conducted for from about 1 to about 10 hours.

Scheme 8 reaction

where R2, R3, R4, R5, X, A, A2and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R10arepresents a group as defined above in (7-3) and (7-44) in connection with R10.

The reaction of obtaining the compound (1o) from the compound (1n) is carried out in the same conditions as described above in connection with the reaction of obtaining compound (9) from compound (8)shown above in scheme 4.

When R10athe compound (1n) is a group defined above (7-44), shown in the above reaction can be carried out in the presence of fluoride. Examples of fluorine compounds are tetraploid ammonium, Tetra-N-butylammonium, peridiniidae etc. of these examples, preferred is Tetra-N-butylammonium. Fluorine compounds are used usually in amounts of at least 1 mole, preferably 1-2 moles, per mole of the compound (1n).

Scheme 9 reaction

where R2, R3, R4, R5, X, A, A2X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above;

R10brepresents a group as defined above in (7-3)-(7-7), (7-9)-(7-20), (7-30)-(7-35) and (7-44) in the connection with R 10;

R10crepresents a group as defined above in (7-2), (7-8), (7-21)-(7-29) and (7-37)-(7-43) in connection with R10;

R10drepresents a group as defined above in (7-1), (7-2), (7-21)-(7-29) and (7-40) in connection with R10; follow group; pyridyloxy group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent optionally substituted by one or more atoms of halogen; thienyl group, optionally substituted in the thiophene ring with one or more halogen atoms; a phenyl group optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, optionally substituted by one or more halogen atoms, ceanography, lower alkyl groups, optionally substituted by one or more halogen atoms, amino groups, optionally substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups, halogen atoms, lower alkoxycarbonyl groups, lower alkanoyloxy, lower alkylsulfonyl groups, lower alkylthio and pyrrolidinyl groups; thiazolidine group; imidazolidinyl group, optional the positive imidazole substituted in the ring by one or more lower alkyl groups; pyrrolidino group, optionally substituted in the pyrrole ring by one or more lower alkyl groups, or cycloalkyl group;

R14arepresents a group as defined above in (10-1)to(10-3) in connection with R14and

R18represents a hydrogen atom or a lower alkyl group,

provided that the total number of carbon atoms of the group CH(R10dR18the compound (1r) does not exceed 6.

The interaction of the compound (1o) with compound (12) is carried out in the same conditions as described above in connection with the interaction of the compound (1j) with compound (11)shown above in scheme 6, provided that the interaction of the compound (1o) with compound (12) number of alkylphenolethoxylate, carboxylic acid (12), the activating agent, condensing agent, the acid chloride of carboxylic acid, etc. take relative to the compound (1o).

The interaction of the compound (1o) with compound (13) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

The interaction of the compound (1o) with compound (14) can be carried out, for example, in a suitable solvent or without solvent in the presence of a reducing agent.

The examples used in this reaction solvents are water, lower alcohols, such as the methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, acetonitrile, aliphatic acids such as formic acid and acetic acid, ethers, such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, mixtures of these solvents, etc.

Examples of reducing agents are aliphatic acids such as formic acid, salts of alkali metals with aliphatic acids such as sodium formate and sodium acetate, hydride reducing agents such as borohydride sodium, cyanoborohydride sodium, triacetoxyborohydride sodium and sociallyengaged, mixtures of these hydride reducing agents, the reducing agent for catalytic hydrogenation, such as palladium black, palladium on carbon, platinum oxide, platinum black, Raney Nickel, etc.

When the reductant used aliphatic acid such as formic acid or salt of an alkali metal with an aliphatic acid such as sodium formate or sodium acetate, in a suitable reaction temperature ranges usually from about room temperature to about 200°C, preferably from about 50 to about 150°C. R is the action usually ends in a period from about 10 minutes to about 10 hours. These aliphatic acids and alkali metal salts with aliphatic acids are usually used in large excess relative to the compound (1o).

When using a hydride reducing agent, a suitable reaction temperature ranges usually from about -80 to about 100°C, preferably from about -80 to about 70°C. the Reaction is usually complete within about 30 minutes to about 60 hours. Hydride reducing agent is used usually in an amount of from about 1 to about 20 mol, preferably from about 1 to about 6 moles, per mole of the compound (1o). In particular, when a hydride reducing agent used sociallyengaged, it is preferable to use the solvent diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme or similar simple ether or benzene, toluene, xylene or the like aromatic hydrocarbon. In the reaction system, the reaction can be entered trimethylamine, triethylamine,N-ethyldiethanolamine or similar amine or molecular sieves 3A (MS-3A), molecular sieves 4A (MS-4A) or similar molecular sieve.

When using a reducing agent for the catalytic hydrogenation, the reaction is usually carried out at a temperature in the range of from about -30 to about 100°C, preferably from about 0 to about 60°C in atmospheres, the hydrogen at a pressure in the range of typically from about atmospheric pressure to about 20 ATM, preferably from about atmospheric pressure to about 10 ATM, or in the presence of formic acid, ammonium formate, cyclohexane, hydrazine hydrate or similar donor of hydrogen. The reaction is normally complete within about 1 to about 12 hours. The reducing agent for the catalytic hydrogenation is used usually in an amount of from about 0.1 to about 40 wt.%, preferably about 1 to about 20 wt.%, regarding the compound (1o).

In the interaction of the compound (1o) with compound (14) compound (14) is used in amount, usually at least equimolar, preferably equimolar to a large excess relative to the compound (1o).

The interaction of the compound (1o) with compound (15) is carried out in the presence or in the absence of a basic compound, but preferably in the absence of a basic compound, in a suitable inert solvent or without solvent.

Examples of inert solvents and basic compounds for the interactions of the compound (1o) with compound (12) (reaction of amide bond formation) include compounds that are used in the same way (d), where the acid chloride of the carboxylic acid is subjected to interaction with the amine (1l).

The amount of compound (15) is usually from about 1 to about 5 mol, preferably from about 1 is about 3 mol, per mole of the compound (1o).

The reaction is expediently carried out at a temperature of from about 0 to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete within from about 5 minutes to about 30 hours.

In the reaction system, the reaction you can enter a complex of boron TRIFLUORIDE in diethyl ether or a similar boron compound.

Scheme 10 reactions

where R2, R3, R4, R5, X, A, A2X1, R14aand the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R14brepresents a group defined above (10-2) and (10-3) in connection with R14.

The interaction of the compound (1s) with compound (16) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Scheme 11 reactions

where R2, R3, R4, R5, X, A, and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, R1drepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one lower alkoxycarbonyl group in the phenyl ring, and R1eis a group, identify lannou above in (1-3) in connection with R 1except for the presence of at least one carboxypropyl phenyl ring.

Obtaining the compound (1v) from the compound (1u) is carried out in the same conditions as described above in connection with obtaining the compound (9) from compound (8)shown above in scheme 4.

Obtaining the compound (1u) from the compound (1v) is carried out in the same conditions as described above in connection with obtaining the compound (1l) from the compound (1m)shown above in scheme 7.

Scheme 12 reactions

where R2, R3, R4, R5, X, A, R6, R7, R1eand the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R1frepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one group-CONR6R7phenyl ring.

The interaction of the compound (1v) with compound (17) is carried out in the same conditions as described above in connection with the interaction of the compound (1j) with compound (11)shown above in scheme 6.

Scheme 13 reactions

where R2, R3, R4, R5, X, A, X1, R18and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above;

R1grepresents a group defined above (1-3) the connection with R 1except for the presence of at least one group -(B)lOther7aphenyl ring, provided that l is as defined above;

R1hrepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one group -(B)lN(R6aR7aphenyl ring;

R1irepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one group -(B)lN(R6bR7aphenyl ring;

R1jrepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one group -(B)lN[CH(R6cR18]R7aphenyl ring, provided that the total number of carbon atoms of the group CH(R6cR18does not exceed 6;

l is as defined above;

R7arepresents a group as defined above in (4-1)-(4-79) in connection with R7;

R6arepresents a group as defined above in (4-2)and (4-4), (4-6), (4-8)-(4-11), (4-19)-(4-32), (4-34)-(4-37), (4-60), (4-62)-(4-72), (4-78) and (4-79) in connection with R6;

R6brepresents a group as defined above in (4-3), (4-5)and (4-7), (4-12)to(4-18), (4-33), (4-38)-(4-59), (4-61), (4-73)-(4-77) in connection with R6; and

R6crepresents a group as defined above in (4-1), (4-2), (4-6), (4-9), (4-20)and (4-21), (4-23)-(4-29), (4-31)and (4-32) and (4-34); pyrid the function group; tetrahydropyranyloxy group; cycloalkyl group; phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups, optionally substituted by one or more halogen atoms, lower alkoxygroup, optionally substituted by one or more halogen atoms, and hydroxy groups; lower alkylenediamine phenyl group; follow group; imidazolidinyl group, optionally substituted in the imidazole ring by one or more members selected from the group consisting of carbamoyl group and lower alkoxycarbonyl groups; pyrrolidinyloxy group, optionally substituted in the pyrolidine ring by one or more lower alkyl groups, or morpholinopropan.

The interaction of the compound (1x) with compound (18) is carried out in the same conditions as described above in connection with the interaction of the compound (1o) with compound (12)shown above in scheme 9.

The interaction of the compound (1x) with compound (19) is carried out in the same conditions as described above in connection with the interaction of the compound (1o) with compound (13)shown above in scheme 9.

The interaction of the compound (1x) with compound (20) is carried out in the same conditions as described above in connection with wsimages is of the compound (1o) with compound (14), shown in scheme 9.

Scheme 14 reactions

where R2, R3, R4, R5, X, A, and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, R1krepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one nitro group in the phenyl ring, and R1lrepresents a group as defined above in (1-3) in connection with R1except for the presence of at least one amino group in the phenyl ring.

Obtaining compound (1cc) from the compound (1bb) can be carried out, for example, (1) recovery of the compound (1bb) in a suitable solvent using a reducing agent for catalytic hydrogenation, or (2) recovering the compound (1bb) in a suitable inert solvent using as a reductant mixture of acids with a metal or metal salt, a mixture of metal or metal salt with an alkali metal hydroxide, sulfide or ammonium salt or the like.

When using the above method (1) examples of solvents are water, acetic acid, alcohols such as methanol, ethanol and isopropanol, hydrocarbons such asnhexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl EPE and dimethyl ether of diethylene glycol, esters, such as ethyl acetate and methyl acetate, aprotic polar solvents, such asN,N-dimethylformamide, mixtures of these solvents, etc. are Examples of a suitable reducing agent for the catalytic hydrogenation include palladium, palladium black, palladium on carbon, platinum on carbon, platinum, platinum oxide, copper chromite, Raney Nickel, etc. of Such a reducing agent may be used individually or in combination of two or more such agents. The reducing agent is used usually in an amount of from approximately 0.02 times equal to the mass of compound (1bb). The reaction temperature is usually from about -20 to about 150°C, preferably from about 0 to about 100°C. the hydrogen Pressure is generally about 1-10 ATM. The reaction is normally complete within about 0.5 to about 100 hours. In the reaction system, the reaction can be introduced acid, such as hydrochloric acid.

When using the above method (2) as the reductant can use a mixture of iron, zinc, tin or tin chloride(II) with a mineral acid, such as hydrochloric acid or sulfuric acid, or a mixture of iron, iron sulfate(II), zinc or tin with an alkali metal hydroxide such as sodium hydroxide, a sulfide such as ammonium sulfide, podnimajutsa or ammonium salt, such as ammonium chloride, or the like. Examples of inert solvents are water, acetic acid, alcohols such as methanol and ethanol, ethers such as dioxane, mixtures of these solvents, etc. Conditions for the reaction of recovery may be appropriately selected in accordance with the used solvent. For example, when as a reducing agent, a mixture of tin chloride(II) and hydrochloric acid is expedient to carry out the reaction at a temperature of about 0-150°C for about 0.5 to 10 hours. The reducing agent is used in amount of at least 1 mol, and is usually about 1-5 mol, per mole of the compound (1bb).

Scheme 15 reactions

where R2, R3, R4, R5, X, A, and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above,

R1mrepresents a group defined above (1-10) in connection with R1except for the presence of at least one halogen atom in the pyridine ring;

R1nrepresents a group defined above (1-10) in connection with R1except for the presence of the pyridine ring, at least one member selected from piperidinyl groups; morpholinopropan; piperazinilnom group, optionally substituted in piperazinone one or more members, selected from the group consisting of phenyl groups and lower alkyl groups; inlinegroup, optionally substituted in the amino group by one or more lower alkyl groups; pyridylamino or pyridylcarbonyl;

R1orepresents a group defined above (1-10) in connection with R1except for the presence of at least one member selected from thienyl groups, phenyl groups, peredelnyh groups and biphenylenes group;

R19represents piperidinyl group; morpholinopropan; piperazinilnom group, optionally substituted in piperazinovom ring by one or more members selected from the group consisting of phenyl groups and lower alkyl groups; belinograph, optionally substituted in the amino group by one or more lower alkyl groups; pyridylamino or pyridylcarbonyl;

R20represents a thienyl group, a phenyl group, pyridyloxy group or biphenylene group;

M represents an alkaline metal such as lithium, potassium, sodium or the like, -MgX1(X1is the same as defined above), -ZnX1(X1the same as defined above) or-B(OH)2;

Y represents a lower alkyl group;

q is 1-4; and

r is 1-3, provided that q+r R the BHA 4.

The interaction of the compound (1dd) with compound (21) is carried out in a suitable solvent in the presence of a basic compound and a catalyst.

The examples used in this reaction solvents and basic compounds include those that are used in the interaction of the compound (1e) with compound (7)shown in scheme 3.

Examples of catalysts are bis(tributylamine)/bis(dibenzylideneacetone)palladium,R-Tris(dibenzylideneacetone)dipalladium,S-Tris(dibenzylideneacetone)dipalladium, palladium acetate(II) and such palladium compounds;R-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (R-BINAP),S-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (S-BINAP),RAC-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (RAC-BINAP), 2,2-bis(diphenylimidazole) and similar compounds; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and similar compounds Xanten;tert-butylphosphine,tert-butyltetrahydrofuran and similar alkylphosphine; their salts; their mixtures, etc.

The primary connection is used usually in an amount of at least 1 mole, preferably 1-2 moles, per mole of the compound (1dd).

The catalyst used in conventional catalytic amount relative to compound (1dd).

The compound (21) is used usually in an amount of at least 1 mole, preferably 1-2 moles, per mole of the compound (1dd).

The reactions is usually carried out at a temperature in the range of from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually complete within about 0.5 to about 20 hours.

The interaction of the compound (1dd) with compound (22a) or (22b) is carried out in a suitable solvent in the presence of a basic compound and a catalyst.

Used in this reaction solvents include, in addition to water, solvents, used in the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Used in this reaction the basic compounds include solvents used in the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Examples of catalysts are tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II) and such palladium compounds.

The primary connection is used usually in an amount of at least 1 mol, preferably 1-5 mol, per mol of compound (1dd).

The catalyst is used usually in amounts of 0.001 to 1 mol, per mol of compound (1dd), preferably 0.01 to 0.5 mol, per mol of compound (1dd).

The compound (21) is used usually in an amount of at least 1 mol, preferably 1-5 mol, per mol of compound (1dd).

The reaction is usually carried out at a temperature in the range of from about -30 to about 200°C, preferably from about 0 to about 150°C. Reacts what I usually complete within about 0.5 to about 20 hours.

As for the case when M is a salt of an alkali metal or MgX1then the reaction is carried out in the absence of a basic compound and a catalyst.

Scheme 16 reactions

where R1, R3, R4, R5, X, A, X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above,

R2arepresents a group as defined above in (2-2), (2-4), (2-5) and (2-7)to(2-32) in connection with R2and

R21represents a lower alkyl group; carboxy(lower)alkyl group; a lower alkoxycarbonyl(lower)alkyl group; a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups, optionally substituted by one or more halogen atoms, lower alkylthio, optionally substituted by one or more halogen atoms, lower alkoxygroup, nitro, lower alkylsulfonyl groups, lower alkoxycarbonyl groups, phenyl(lower)alkenyl groups, lower alkanoyloxy and 1,2,3-thiadiazolyl groups; piperidinyl(lower)alkyl group, optionally substituted in piperidinium ring by one or more lower alkyl groups; aminosilane lower alkyl is ing group, optionally substituted by one or more lower alkyl groups; lower alkenylphenol group; pyridyl(lower)alkyl group, optionally substituted in the pyridine ring with one or more lower alkyl groups, each lower alkyl substituent optionally substituted by one or more halogen atoms; lower alkylamino group; phenyl(lower)alkylamino group; phenyl(lower)alkenylphenol group; furyl(lower)alkyl group, optionally substituted in the furan ring by one or more lower alkoxycarbonyl groups; tetrazolyl(lower)alkyl group, optionally substituted in tetrazolium the Deputy ring, selected from the group consisting of a phenyl group, a phenyl(lower)alkyl groups, and cycloalkyl(lower)alkyl group; 1,2,4-oxadiazolyl(lower)alkyl group, optionally substituted in 1,2,4-oxadiazole ring of the phenyl group, and a phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups; isoxazolyl(lower)alkyl group, optionally substituted in isoxazoline ring by one or more lower alkyl groups; 1,3,4-oxadiazolyl(lower)alkyl group, optionally substituted in 1,3,4-oxadiazole ring of the phenyl group and phenyl for estately optionally substituted in phenyl ring by one or more lower alkyl groups; lowest alkanoyl(lower)alkyl group; thiazolyl(lower)alkyl group, optionally substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more halogen atoms; piperidinyl group, optionally substituted in piperidinium the ring one or more benzoline groups, each bentely Deputy optionally substituted in the phenyl ring by one or more halogen atoms; thienyl(lower)alkyl group; phenylthio(lower)alkyl group; carbamoylation lower alkyl group, optionally substituted by one or more lower alkyl groups; benzoyl(lower)alkyl group; pyridylcarbonyl(lower)alkyl group; imidazolyl(lower)alkyl group, optionally substituted in the imidazole ring by one or more phenyl(lower)alkyl groups; phenoxy(lower)alkyl group; a phenyl(lower)alkoxy-substituted lower alkyl group; 2,3-dihydro-1H-indenolol group or isoindoline(lower)alkyl group, optionally substituted in isoindoline the ring one or more exography.

The interaction of compounds (1gg) with compound (23)is carried out in the same conditions, as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Compounds (2), (4) and (8)used, as shown in the diagram above, as starting substances can be obtained, for example, by the reaction scheme below.

Scheme 17 reactions

where R1a, R2, R4, R5X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, R22represents the lowest alkylsulfonyl group, optionally containing at least one halogen atom, X2represents a halogen atom and M is equal to 1-4.

The interaction of the compound (24) with compound (25) or (26) and the interaction of the compound (30) with compound (25) or (26) can be carried out under the same conditions as described above in one of the methods (d), where the interaction of the compound (1j) with compound (11)shown above in scheme 6, halogenmethyl carboxylic acid (1j), i.e. the carboxylic gelegenheid, is subjected to the interaction with the amine (11).

Getting a connection (28) from compound (27) to obtain a compound (32) from the compound (31) can be provided by interaction of the compound (27) with cyanide the metal and the compound (31) with a metal cyanide, accordingly, in a suitable solvent in the presence of a catalyst.

Examples of cyanide metals are sodium cyanide, potassium cyanide, hydrogen cyanide silver cyanide zinc, copper cyanide, etc.

Examples of the solvents and catalysts used in these reactions include those that are used in the interaction of the compound (1dd) with compound (22), shown above in figure 15.

The catalyst is used in an amount of usually 0.01-1 mol, preferably 0.01 to 0.5 mol, per mol of compound (27) or (31).

The metal cyanide is used in the amount of usually at least 1 mol, preferably 1-3 mol, per mol of compound (27) or (31).

The reaction is conducted usually at a temperature from about room temperature to 200°C, preferably from about room temperature to about 150°C. the Reaction is usually completed within a time range from about 1 hour to about 1 week.

Obtaining compound (2a) from compound (28) to obtain a compound (2b) from the compound (32) is carried out in a suitable solvent in the presence of a reducing agent.

The examples used in this reaction solvents are formic acid and like aliphatic acid; dioxane, tetrahydrofuran, diethyl ether, dimethyl ether of diethylene glycol and the like ethers; benzene, toluene, xylene and similar aromatice the Kie hydrocarbons, dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like, halogenated hydrocarbons and mixtures of these solvents.

Examples of reducing agents are hydride diisobutylaluminum and similar hydrides alkylamine, Raney Nickel, etc. the Reducing agent is used usually in an amount at least equal to the mass of compound (28) or (32), preferably in amounts of from equal weight to 5 times the specified mass.

The reaction is carried out at a temperature in the range of typically from about room temperature to 200°C, preferably from about room temperature to about 150°C. the Reaction is usually completed within from about 0.5 to about 20 hours.

Compounds (2a) and (2b) can be obtained by reduction of compounds (28) and (32), respectively, under the same conditions as described above in connection with the reaction shown in scheme 1, to obtain the compound (1b) from the compound (1a) in the case of using a reducing agent for catalytic hydrogenation. It is desirable to introduce into the reaction system inorganic acid such as hydrochloric acid or sulfuric acid, in the amount of usually at least 1 mole, preferably 1-2 moles, per mole of the compound (28) or (32).

Obtaining the compound (29) of the compounds (2a) to obtain a compound (33) from the compound (2b) is carried out in a suitable is rastvoritele in the presence of acid to separate the interaction of compounds (2a) and compound (2b) with alcohol, represented by the formula

HO-(CH2)m-OH (51),

where M is as defined above.

Used in these reaction solvents and acids include those that are used when interacting compounds (2) with compound (3)shown above in scheme 1.

Usually it is advisable to use the acid in catalytic amount. The amount of compound (51) is generally at least 1 mol, preferably 1-5 mol, per mol of compound (2a) or (2b).

The reaction is carried out at a temperature in the range of typically from about room temperature to 200°C, preferably from about room temperature to about 150°C. the Reaction is usually completed within from about 0.5 hours to about 10 hours.

Interaction of the compound (24) with compound (10), compound (27) with compound (10), compound (28) with compound (10), compound (2a) from compound (10) and the compound (29) with compound (10) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown in scheme 3.

Obtaining compound (2a) from compound (29) to obtain a compound (2b) from compound (33) is carried out in the same conditions as described above in connection with the reaction of obtaining compound (9) from compound (8)shown in scheme 4. In these reactions as acids can be used on lesofat p-toluensulfonate pyridinium and such sulfonates.

Scheme 18 reactions

where R1a, R2, R4, R5, R15X1and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.

Getting from compound (34) of the compound (2c), where R15represents a hydrogen atom, and receiving from the compound (35) of the compound (2d), where R15represents a hydrogen atom, is carried out in a suitable solvent in the presence of a catalyst to separate the interaction of the compound (34) and compound (35) with the compound represented by the formula

X1(X2)CHOR24(52),

where X1and X2are as defined above, and R24represents a lower alkyl group.

Used in this reaction solvents include the solvents used in the interaction of the compound (1dd) with compound (22), shown above in figure 15.

Examples of catalysts are titanium tetrachloride and similar compounds of titanium, tin chloride(IV) and similar compounds of tin, aluminum chloride and similar compounds of aluminum, etc. the Catalyst is used usually in an amount of at least 1 mol, preferably 1-5 mol, per mol of compound (34) or (35).

Compound (52) is used in the share of the ve usually at least 1 mol, preferably 1-5 mol, per mol of compound (34) or (35).

The reaction is carried out at a temperature in the range of typically from about 0 to about 70°C, preferably from about 0 to about 50°C. the Reaction is usually complete within about 1 minute to about 1 hour.

Getting from compound (34) of the compound (2c), where R15represents a hydrogen atom, and receiving from the compound (35) of the compound (2d), where R15represents a hydrogen atom, can be carried out in the presence of a halogenation agent and acid separate interaction of the compound (34) and compound (35) withp-formaldehyde and hexamethylenetetramine.

Examples of the halogenation agent used in these reactions are hydrochloric acid, Hydrobromic acid, etc. are Examples of acids are sulfuric acid, phosphoric acid and like inorganic acids,p-toluensulfonate acid, formic acid, acetic acid and such organic acids and mixtures of these acids. Halogenation agent and the acid is usually used in large excess.

p-Formaldehyde is used usually in an amount of at least 0,1 times the mass of the compound (34) or (35), preferably in amounts of from 0.1 times the specified mass equal to the mass.

Hexamethylenetetramine ispolzuut amount of usually at least 1 mol, preferably 1-5 mol, per mol of compound (34) or (35).

The reaction is carried out at a temperature in the range of typically from about room temperature to about 150°C, preferably from about room temperature to about 100°C. the Reaction is usually complete within about 0.5 to about 10 hours.

Getting from compound (34) of the compound (2c), where R15represents a hydrogen atom, and receiving from the compound (35) of the compound (2d), where R15represents a hydrogen atom, can be carried out in a suitable solvent in the presence of acid separate interaction of the compound (34) and compound (35) with hexamethylenetetramine.

These effects are usually referred to as reactions Duff. Used in these reactions acids are acids which are preferably used in the reactions Duff, for example acetic acid, a mixture of boric acid-anhydrous glycerin, triperoxonane acid, etc. Acid is used in amount, usually at least equimolar, preferably in the range of from equimolar to a large excess per mole of the compound (34) or (35).

Used in these reaction solvents include the solvents used in the interaction of the compound (1dd) with compound (22), shown above in figure 15.

The reaction is carried out at a temperature in the range of usually from PR is about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually completed within from about 0.5 to about 10 hours.

Compound (2c), where R15represents a lower alkyl group, the compound (2d), where R15represents a lower alkyl group, get a single interaction, in a suitable solvent in the presence of acid compounds (34) and compound (35) with the compound represented by the formula

X1COR15a(53),

where X1is the same as defined above, and R15arepresents a lower alkyl group.

These effects are usually referred to as the reactions of the Friedel-and implement them in a suitable solvent in the presence of Lewis acid.

Used in these reactions, Lewis acid include any Lewis acid, typically used in these reactions Friedel -, and their examples include aluminum chloride, zinc chloride, iron chloride, tin chloride(IV), tribromide boron, boron TRIFLUORIDE, sulfuric acid, etc.

Examples of the used solvents include carbon disulfide, nitrobenzene, chlorobenzene and the like aromatic hydrocarbons, dichloromethane, dichloroethane, carbon tetrachloride, tetrachlorethane and like halogenated hydrocarbons, nitroethane, nitromethane and the like is haunted aliphatic nitrocompounds, mixed solvents of these solvents, etc.

The Lewis acid is used usually in an amount of from 1 to 6 mol per mol of compound (34) or (35).

Compound (53) is used in an amount of usually at least 1 mol, preferably 1-5 mol, per mol of compound (34) or (35).

The reaction is carried out at a temperature in the range of typically from about 0 to about 150°C, preferably from about 0 to about 100°C. the Reaction is usually completed within from about 0.5 to about 25 hours.

The interaction of the compound (34) with compound (10) and the interaction of the compound (2c) with compound (10) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Scheme 19 reactions

where R1a, R2, R4, R5X1X2and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.

Obtaining the compound (2e) from the compound (36) and the compound (2f) from the compound (37) is performed by the interaction of the compound (36) with gaseous carbon monoxide and compounds (37) with gaseous carbon monoxide, respectively, in a suitable solvent in the presence of a catalyst and a salt of an alkali metal with acid.

Examples of solvents and ka is alization, used in these reactions include those that are used in the interaction of the compound (1dd) with compound (22), shown above in figure 15.

Examples of alkali metal salts with acids are sodium formate, potassium formate, sodium acetate, potassium acetate, etc. Salt of an alkali metal acid is used in amount of usually at least 1 mol, preferably 1-5 mol, per mol of compound (36) or (37).

The catalyst is usually used in an amount of 0.01-1 mol per mol of compound (36) or (37).

Gaseous carbon monoxide is usually used in a large excess relative to the compound (36) or (37).

The reaction is carried out at a temperature in the range of typically from about room temperature to about 200°C, preferably from about room temperature to about 150°C. the Reaction is usually completed within from about 0.5 hours to about 10 hours.

The interaction of the compound (36) with compound (10) and the interaction of the compound (2e) with compound (10) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

Scheme 20 reactions

where R1, R2, R4, R5X1, R16X2and the relationship between the clauses 3 and 4 barbastelle SC the summer are such as specified above.

The interaction of the compound (38) with compound (39) is carried out in the same conditions as described above in connection with the interaction of the compound (34) with compound (53), shown above in figure 18.

Obtaining connection (41) of the compound (40) is performed by the recovery of the compound (40) in the same conditions as described above in connection with obtaining the compound (1b) from the compound (1a) using a hydride reducing agent, shown above in scheme 1.

Obtaining the compound (4a) of the compound (41) is performed by the interaction of the compound (41) with a halogenation agent in a suitable solvent or without solvent.

Examples of halogenation agents are hydrochloric acid, Hydrobromic acid and the like, mineral acids,N,N-diethyl-1,2,2-trichloroaniline, pentachloride phosphorus, pentabromide phosphorus, phosphorus oxychloride, thionyl chloride and a mixture of sulphonylchloride (methylchloride, Teilhard and the like) with the basic compounds, etc.

Used in this reaction the basic compounds are those that are used when interacting compounds (2) with compound (3)shown above in scheme 1.

Examples of the used solvents are dioxane, tetrahydrofuran, diethyl ether and like ethers, chloroform, methylene chloride, tetrachloro the carbon and the like, halogenated hydrocarbons, etc.

When the halogenation agent is a mixture of sulphonylchloride and grounds, sulfonylmethane used in the amount of usually at least 1 mole, preferably 1-2 moles, per mole of the compound (41). The primary connection is used usually in a catalytic amount, preferably in an amount of from catalytic to equimolar relative to the compound (41). When using other halogenation agents, halogenation agent is used in an amount of generally at least 1 mol, preferably 1-10 mol, per mol of compound (41).

The reaction is expediently carried out at a temperature in the range of usually from room temperature to 150°C, preferably from room temperature to 100°C. the Reaction is usually complete within about 1 to about 10 hours.

Scheme 21 reactions

where R1, R2, R4, R5X1, R15, R16, R17, A4and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.

The interaction of the compound (42) with compound (46) is carried out in the same conditions as described above in connection with the interaction of the compound (1e) with compound (7)shown above in scheme 3.

The reaction of obtaining compound (8) from compound (43) is carried out in a suitable solvent in the Pris is under halogenation agent in the presence or in the absence of the primary connection.

The examples used in this reaction halogenation agents are Br2, Cl2and similar molecules of halogen, idhari, sulfurylchloride, copper compounds such as copper bromide(I),N-bromosuccinimide and the likeN-halogenating etc.

Examples of the used solvents are diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, diglyme and the like ethers, dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like, halogenated hydrocarbons, acetic acid, propionic acid and like aliphatic acids, carbon disulfide, etc.

Examples of basic compounds include those that are used when interacting compounds (2) with compound (3)shown in scheme 1, above.

Halogenation agent is used in amounts of generally 1-10 mol, preferably 1-5 mol, per mol of compound (43).

The primary connection is used in amounts of generally 1-10 mol, preferably 1-5 mol, per mol of compound (43).

The reaction is carried out at a temperature in the range of typically from about 0 to about 200°C, preferably from about 0 to about 100°C. the Reaction is usually complete within from about 5 minutes to about 20 hours.

The interaction of the compound (44) with compound (46) is carried out in a suitable solvent is the presence of a basic compound.

The examples used in this reaction the basic compounds are sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate and the like inorganic basic compounds, sodium acetate and similar salts of alkali metals with aliphatic acids, piperidine, triethylamine, trimethylamine, pyridine, dimethylaniline,N-ethyldiethanolamine, dimethylaminopyridine,N-methylmorpholine, DBN, DBU, DABCO and the like organic bases, etc. These basic compounds may be used individually or in combination of two or more such compounds.

Suitable are any inert solvents, if only they do not impact adversely on the reaction, for example, water, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, aliphatic acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones, such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide,N,N-dimethylformamide, hexamethylphosphoric triamide, a mixture of the decree is different solvents, etc.

The primary connection is used usually in an amount of from about 0.1 to about 5 mol per mol of compound (45).

Compound (46) is used in an amount of usually at least 1 mol, preferably about 1-5 mol, per mol of compound (45).

The reaction temperature is usually from about room temperature to about 200°C, preferably from about 50 to about 150°C. the Reaction is usually complete within from about 5 minutes to about 30 hours.

Obtaining compounds (43) from the compound (46) is performed by the recovery of the compound (46) in the same conditions as described above in connection with the reaction of obtaining compound (1b) from the compound (1a), shown in scheme 1 where the use of a reducing agent for catalytic hydrogenation.

Scheme 22 reactions

where R1m, R1n, R1o, R2, R4, R5, M, m and the bond between positions 3 and 4 barbastelle skeleton are as defined above.

The interaction of the compound (47) with compound (21) is carried out in the same conditions as described above in connection with the interaction of the compound (1dd) with compound (21), shown above in figure 15.

The interaction of the compound (47) with compound (22) is carried out in the same conditions as described above in connection with the interaction of the compound (1dd) with compound (21), while the data above in scheme 15.

Interaction of the compound (23) with the initial connection(24), (34), (36), (38), (42) and (47), where R2represents a hydroxyl group, can be obtained from the corresponding compounds where R2represents a group as defined above in (2-2), (2-4), (2-5) and (2-7)to(2-32). Data reaction is carried out in the same conditions as described above in connection with the interaction of the compound (1gg) with compound (23), shown above in scheme 16.

Interaction of the compound (10) with the parent compounds (38) and (42), where R1represents a hydrogen atom, can be obtained from the corresponding compounds where R1represents a group defined above (1-2)-(1-29). Data reaction is carried out in the same conditions as described above in connection with the interaction of the compound (1h) with compound (10)shown above in scheme 5.

Each of the target compounds obtained in the above schemes reactions can be isolated from the reaction mixture and purified by performing, for example, after cooling the reaction mixture, the selection method such as filtration, concentration, extraction and so on, with the separation of the crude reaction product and the subsequent purification of the crude reaction product is a conventional method such as column chromatography, recrystallization, etc.

Carbocyanine compound of formula (1) to the present is the invention includes stereoisomers and optical isomers and a solvate, such as hydrates, etc.

Among the compounds of the present invention compounds that contain the main(s) the group or groups can easily form a salt with a conventional pharmaceutically acceptable acids. Examples of such acids include hydrochloric acid, Hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and other inorganic acid, methanesulfonate acid,p-toluensulfonate acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malic acid, lactic acid and other organic acid, etc.

Among the compounds of the present invention compounds which contain acid(s) the group or groups can easily form a salt when interacting with a pharmaceutically acceptable basic compounds. Examples of such basic compounds include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc.

Next, a description pharmaceutical preparations containing the compound of the present invention as the active component.

These pharmaceutical preparations are produced from the compound of the present invention in the form of normal forms using commonly used razbam the residents or excipients, such as fillers, enlargers volume, binders, wetting agents, disintegrant, surfactants, lubricants, etc.

The form of these pharmaceutical preparations may be selected from various shapes in accordance with the purpose of therapy. Specific examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injectable form (solution, suspension, etc. and the like.

For the manufacture of tablets can be used any of the many well-known media, including, for example, lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose and other excipients; water, ethanol, propanol, simple syrup, glucose solutions, solutions of starch solutions, gelatin, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone and other binders; dry starch, sodium alginate, powdered agar, laminography powder, sodium bicarbonate, calcium carbonate, polyoxyethylenesorbitan esters of fatty acids, sodium lauryl sulfate, the monoglyceride of stearic acid, starch, lactose and other disintegrant; white sugar, stearin, cacao butter, hydrogenated oils and other inhibitors of disintegration; Quaternary ammonium based is the W, sodium lauryl sulfate and other promoters of absorption; glycerin, starch and other wetting agents; starch, lactose, kaolin, bentonite, colloidal silicic acid and other adsorbents; purified talc, stearates, powdered boric acid, polyethylene glycol and other lubricants; and so on

These tablets can be, when needed, are covered by the conventional material for coating with obtaining, for example, tablets, sugar coated tablets, gelatin-coated tablets with intersolubility coated tablets film-coated, two - or multi-layer tablets, etc.

For the manufacture of pills can be used any of the many well-known media, including, for example, glucose, lactose, starch, cacao butter, hydrogenated vegetable oils, kaolin, talc and other excipients; powdered Arabian gum, powdered tragakant, gelatin, ethanol and other binders; laminaran, agar-agar and other disintegrant; etc.

For the manufacture of suppositories can be used any of the many well-known media, including, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthetic glycerides, etc.

For the manufacture of injectable form of solution, emulsion or suspension of sterilized the form and preferably make isotonic(Oh) with blood. Any of numerous known and widely used diluents may be used for the manufacture of a solution, emulsion or suspension. Examples of such diluents include water, ethanol, propylene glycol, ethoxylated isostearoyl alcohol, polioksidony isostearoyl alcohol, polyoxyethylenesorbitan esters of fatty acids, etc. In this case, the pharmaceutical preparation may contain sodium chloride, glucose or glycerin in an amount sufficient to obtain an isotonic solution, and may contain conventional soljubilizatory, buffers, analgesic substances, etc. and, in addition, if necessary, coloring agents, preservatives, corrigentov, sweeteners, etc. and/or other medicines.

The relative content of the compounds of the present invention in the pharmaceutical preparation is not limited and may be appropriately selected from a wide range. Usually preferably, the pharmaceutical preparation contains the compound of the present invention in the proportion of 1-70 wt.%.

Route of administration of the pharmaceutical preparation of the present invention and do not limit the drug is administered by a suitable form of the drug, age and sex of the patient, disease States and other conditions. For example, tablets, pills, solutions, suspensions, EMU is sii, granules and capsules are administered orally. Forms for injection is injected separately or in a mixture with conventional solutions for intravenous infusion, such as glucose, amino acid solutions or the like, or, if necessary, enter separately intramuscularly, intracutaneously, subcutaneously or intraperitoneally. Suppositories administered intrarectally.

The dose of a pharmaceutical product shall be chosen in accordance with the method of administration, the age and gender of the patient, severity of disease and other conditions and it is usually about 0.001 to 100 mg/kg of body weight per day, preferably 0.001 to 50 mg/kg of body weight per day, and is entered as a single dose or in divided doses.

Because the dose varies depending on various conditions, it may be sufficient dose is less than the specified range, or you may need a dose exceeding the specified range.

Carbocyanine derivative of the present invention induces the TFF products, such as products TFF2, and therefore useful as an active component of the inductor (control enhancement) TFF, in particular inductor TFF2.

The connection according to the present invention can be used on the basis of its inducing products TFF activity as agent for the prevention or treatment of various diseases, such as damage was slit the stand shell, in human therapy and veterinary medicine. Specific examples of diseases for which can be obtained preventive or therapeutic effects based on inducing products TFF activity, in particular by inducing the production of TFF2 activity include acute and chronic diseases of the digestive tract of various origins (e.g., ulcers, caused by the drug, peptic ulcer, ulcerative colitis, Crohn's disease, enteritis, caused by the drug, ischemic colitis, irritable bowel syndrome, ulcers that developed after endoscopic diakonale, acute gastritis, chronic gastritis, reflux esophagitis, esophageal ulcer syndrome Beretta, gastrointestinal mucositis (such as gastrointestinal mucositis caused by chemotherapy, radiation therapy etc), hemorrhoidal disease, etc.), diseases of the oral cavity (e.g., stomatitis (such as stomatitis caused by chemotherapy, radiation therapy, aphthous stomatitis, etc.), Sjogren syndrome, xerostomia, etc.), diseases of the upper respiratory tract (e.g., rhinitis, pharyngitis etc), respiratory disease (e.g. asthma, chronic obstructive pulmonary disease etc), eye diseases (such as dry eye, keratoconjunctivitis, etc.), cancer RA is s, etc.

The compound of the present invention has minor side effects and exhibits high safety.

Carbocyanine the compounds of formula (1) and their salts covered by the present invention, can be introduced in combination with TFF-peptides (TFF1, TFF2, TFF3, and so on), another type of compounds which induce the activity in relation to the products TFF, and/or other drugs (such as anti-inflammatory agents, anti-ulcer remedies and so on).

Patents, patent applications and publications cited in this specification, are included in this description by reference.

Figure 1 shows a schematic comparison between the nucleotide sequence of the PCR product cloned into plasmid pCR-Blunt-TFF2pro (number 1 in the sequence listing), and a copy of a region of the promoter hTFF2 registered in the Bank of genes (GenBank accession AB038162).

The best way of carrying out the invention

The following examples serve to further illustrate the present invention.

Reference example 1

Synthesis of 8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-carboxaldehyde

8-Methoxy-1-methyl-1H-quinoline-2-it (21,14 g, 0.11 mol) and paraformaldehyde (10.6 g) suspended in concentrated hydrochloric acid (105 ml) was added 4 ml of concentrated sulfuric acid, followed by stirring at 70-80°C is for 2.5 hours. After cooling to room temperature, to the reaction mixture were added ice water and was extracted with dichloromethane. The organic layer was washed with a saturated solution of sodium chloride and dried over anhydrous sodium sulfate. Then drove under reduced pressure the solvent. The residue was dissolved in 400 ml of chloroform and to the solution was added hexamethylenetetramine (4,25 g, 0.03 mol), followed by boiling under reflux for 2.5 hours. After cooling to room temperature drove the solvent under reduced pressure. To the residue was added 50% acetic acid (110 ml) and the mixture was stirred at 100°C for 2 hours. After cooling to room temperature was added water and was separated by filtration of the insoluble matter, and then it was dried with getting 13,81 g (yield: 57%) of 8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-carboxaldehyde in the form of light yellow powder.

1H-NMR (DMSO-d6) δ ppm: of 3.80 (3H, s)to 4.01 (3H, s), 6,79 (1H, d, J=9.9 Hz), was 7.45 (1H, d, J=8,4 Hz), 7,86 (1H, d, J=8,4 Hz), 9,05 (1H, d, J=9.9 Hz), 10,14 (1H, s).

Reference example 2

Synthesis of diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethylene)malonate

8-Methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-carboxaldehyde (18,9 g), diethylmalonate (26.5 ml) and piperidine (2.7 ml) was added to pyridine (90 ml) and the resulting mixture was stirred at 90-100°C for 6 hours. After cooling the to room temperature the reaction mixture was added to cold concentrated hydrochloric acid and precipitated precipitated solid substance was separated by filtration, washed with water and dried to obtain 16,62 g (yield: 53%) of diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethylene)malonate in the form of a yellow powder.

1H-NMR (DMSO-d6) δ ppm: 1,10 (3H, t, J=7.2 Hz), of 1.28 (3H, t, J=7.2 Hz), 3,80 (3H, s)to 3.92 (3H, s), 4,05 of 4.3 (4H, m), 6,69 (1H, d, J=9.8 Hz), 7,18 (1H, d, J=8.5 Hz), 7,30 (1H, d, J=8.5 Hz), to 7.84 (1H, d, J=9.8 Hz), 8,14 (1H, s).

Reference example 3

Synthesis of diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate

Diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethylene)malonate (16,62 g) and 10% palladium on carbon (1.6 g) was added to 300 ml of ethanol, followed by catalytic hydrogenation at room temperature and atmospheric pressure for 6 hours. The catalyst was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:1) to obtain the 13,59 g (yield: 81%) of diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate in the form of a light yellow oil.

1H-NMR (CDCl3) δ ppm: 1,15-1,3 (6H, m), of 3.45 (2H, d, J=7,6 Hz), 3,60 (1H, t, J=7,6 Hz)to 3.89 (3H, s), of 3.95 (3H, s), 4,1-of 4.25 (4H, m), of 6.75 (1H, d, J=9.8 Hz), of 6.96 (1H, d, J=8,3 Hz),? 7.04 baby mortality (1H, d, J=8,3 Hz), 7,86 (1H, d, J=9.8 Hz).

Reference example 4

Synthesis of diethyl-2-chloro-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate

Sodium hydride (60% in oil) (1.0 g) was added under ice cooling to tertrahydrofuran ring (THF) races the thief (140 ml) 13,59 g of diethyl-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate and the mixture was stirred until cessation of hydrogen evolution. Was added N-chlorosuccinimide (5.6 g), followed by stirring for 1 hour. The reaction mixture was added to cold dilute hydrochloric acid and was extracted with dichloromethane. After drying over anhydrous sodium sulfate dry product was concentrated under reduced pressure, was added to the residue diisopropyl ether, precipitated precipitated solid substance was separated by filtration and dried to obtain 12,77 g (yield: 86%) of diethyl-2-chloro-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate in the form of light yellow powder.

1H-NMR (CDCl3) δ ppm: of 1.28 (3H, t, J=7.2 Hz), 3,86 (2H, s)to 3.89 (3H, s)to 3.92 (3H, s), from 4.2 to 4.3 (4H, m), of 6.71 (1H, d, J=9.8 Hz), 6,98 (1H, d, J=8,4 Hz), 7,10 (1H, d, J=8,4 Hz), to 7.93 (1H, d, J=9.8 Hz).

Reference example 5

Synthesis of 2-chloro-3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propionic acid

Diethyl-2-chloro-2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)malonate (5,1 g) was added to a mixture of 20 ml of acetic acid and 15 ml of 6N. hydrochloric acid, followed by boiling under reflux for 9 hours. After cooling to room temperature, to the reaction mixture was added water, followed by cooling with ice. Precipitated precipitated solid substance was separated by filtration, washed with water and dried to obtain 3.1 g of 2-chloro-3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propionic acid as light yellow p the Rosca.

1H-NMR (DMSO-d6) δ ppm: 3,45-the 3.65 (2H, m), of 3.77 (3H, s), 3,86 (3H, s), 4,5 with 4.65 (1H, m), 6,62 (1H, d, J=9.8 Hz), 7,14 (1H, d, J=8,3 Hz), 7,21 (1H, d, J=8,3 Hz), 8,03 (1H, d, J=9.8 Hz), and 13.4 (1H, users).

Reference example 6

Synthesis of diethyl-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate

Sodium hydride (60% in oil) (0.5 g) was added under ice cooling to tertrahydrofuran ring (THF) solution (30 ml) diethylmalonate (2.2 ml) and the mixture was stirred until cessation of hydrogen evolution. Was added 5-(2-Iodate)-8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline (1.54 g), followed by stirring at room temperature over night. The reaction mixture was added to cold dilute hydrochloric acid and was extracted with dichloromethane. After drying over anhydrous sodium sulfate dry product was concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=50:1→40:1). The purified product was kept under reduced pressure to obtain 1.73 g (yield: quantitative) of diethyl-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate in the form of a yellow oil.

1H-NMR (CDCl3) δ ppm: 1,2-1,4 (6H, m), from 2.1 to 2.25 (2H, m), 2.8 to 3.0 (2H, m), 3,3-3,5 (1H, m), 3,88 (3H, s), 3,93 (3H, s), a 4.1 and 4.4 (4H, m), of 6.75 (1H, d, J=9.7 Hz), 6,9-7,1 (2H, m), 7,92 (1H, d, J=9.7 Hz).

Reference example 7

Synthesis of diethyl-2-chloro-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate

Hydra is d sodium (60% in oil) (0.21 g) was added under cooling with ice to a THF solution (30 ml) to 1.79 g of diethyl-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate and the mixture was stirred until cessation of hydrogen evolution. Was added N-chlorosuccinimide (0.7 g), followed by stirring for 1.5 hours. The reaction mixture was added to cold dilute hydrochloric acid and was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 2.38 g (yield: quantitative) of diethyl-2-chloro-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate in the form of a yellow oil.

1H-NMR (CDCl3) δ ppm: to 1.31 (6H, t, J=7,1 Hz), 2,47 (2H, t, J=8.7 Hz), 2,98 (2H, t, J=8.7 Hz), 3,88 (3H, s), 3,93 (3H, s), of 6.75 (1H, d, J=9.7 Hz), 6,9-7,1 (2H, m), 7,87 (1H, d, J=9.7 Hz).

Reference example 8

Synthesis of 2-chloro-4-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)butyric acid

Diethyl-2-chloro-2-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]malonate (2.38 g) was added to a mixture of acetic acid (10 ml) and 6N. hydrochloric acid (15 ml) and the resulting mixture was boiled under reflux overnight. After cooling to room temperature, to the reaction mixture were added water and a small amount of ethanol, followed by cooling with ice. Precipitated precipitated solid substance was separated by filtration, washed with water and dried to obtain 0,99 g (yield: 55%) of 2-chloro-4-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)butyric acid as a gray powder.

1H-NMR (DMSO-d6) δ ppm: 1,9-2,3 (2H, m), 2,8-3,1 (2H, m), of 3.77 (3H, s), 3,85 (3H, s), 4,4-4,6 (1H, m) of 6.61 (1H, d, J=9.7 Hz), 7,05 (1H, d, J=7,1 Hz), 7,18 (1H, d, J=7,1 Hz), 7,98 (1H, d, J=9.7 Hz), and 13.4 (1H, users).

Reference example 9

Synthesis of diethyl-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate

Sodium hydride (60% in oil) (0.39 g) was added under cooling with ice to a THF solution (30 ml) diethylmalonate (of 1.85 ml) and the mixture was stirred until cessation of hydrogen evolution. Was added 5-(3-improper)-8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline (2,89 g), followed by stirring at room temperature for 4.5 hours. The reaction mixture was added to cold dilute hydrochloric acid and was extracted with dichloromethane. After drying over anhydrous sodium sulfate dry product was concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=20:1). The purified product was concentrated under reduced pressure to get 2,94 g (yield: 93%) of diethyl-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate in the form of a yellow oil.

1H-NMR (CDCl3) δ ppm: of 1.27 (6H, t, J=7,1 Hz), 1,6-1,8 (2H, m), are 1.95 and 2.1 (2H, m), 2,87 (2H, t, J=7,7 Hz), of 3.56 (1H, t, J=7.5 Hz), with 3.89 (3H, s), of 3.95 (3H, s), a 4.1 and 4.4 (4H, m), of 6.73 (1H, d, J=9.8 Hz), 7,00 (2H, s), to 7.84 (1H, d, J=9.8 Hz).

Reference example 10

Synthesis of diethyl-2-chloro-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate

Sodium hydride (60% in oil) (0.33 g) was added under cooling with ice to a THF solution (30 ml) d is ethyl-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate (2,94 g) and the mixture was stirred until cessation of hydrogen evolution. Was added N-chlorosuccinimide (1.2 g), followed by stirring for 2 hours. The reaction mixture was added to cold dilute hydrochloric acid and was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to get as 4.02 g (yield: quantitative) of diethyl-2-chloro-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate in the form of a yellow oil.

1H-NMR (CDCl3) δ ppm: 1.26 in (6H, t, J=7,1 Hz), 1,6-1,9 (2H, m), 2,31 (2H, t, J=8.0 Hz), is 2.88 (2H, t, J=7,7 Hz), 3,88 (3H, s), of 3.94 (3H, s), 6,72 (1H, d, J=9.8 Hz), 6,99 (2H, s), 7,79 (1H, d, J=9.8 Hz).

Reference example 11

Synthesis of 2-chloro-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)valerianic acid

Diethyl-2-chloro-2-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]malonate (as 4.02 g) was added to a mixture of acetic acid (15 ml) and 6N. hydrochloric acid (20 ml), followed by boiling under reflux for 24 hours. After cooling to room temperature, to the reaction mixture was added water, followed by cooling with ice. Precipitated precipitated solid substance was separated by filtration, washed with water and dried to obtain 2.30 g (yield: 75%) of 2-chloro-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)valerianic acid as a pale yellow powder.

1H-NMR (DMSO-d6) δ ppm: 1.6 to about 2.2 (4H, m), of 2.7-3.1 (2H, m), of 3.77 (3H, s), of 3.84 (3H, s), 4,5 with 4.65 (1H, m), 6,9 (1H, d, J=9.7 Hz), 7,05 (1H, d, J=8.1 Hz), 7,17 (1H, d, J=8.1 Hz), to 7.99 (1H, d, J=9.7 Hz), and 13.2 (1H, users).

Reference example 12

Synthesis of 8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

8-Methoxy-3,4-dihydro-1H-quinoline-2-it (5 g) was dissolved in dichloromethane (100 ml) and to the solution was added dichlorodimethyl ether (6.4 ml) at room temperature and then cooled in a water bath with ice. Was added dropwise a titanium tetrachloride (85 ml) at a temperature not exceeding 10°C and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into ice water and the aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. To the residue was added diethyl ether and the resulting solid substance was separated by filtration and dried to obtain 5.2 g (yield: 90%) of 8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde.

1H-NMR (CDCl3) δ ppm: 2,63 (2H, t, J=7.4 Hz), of 3.54 (2H, t, J=7.4 Hz), of 3.97 (3H, s), 6,92 (1H, d, J=8.5 Hz), to 7.50 (1H, d, J=8.5 Hz), to 7.84 (1H, users), 10,02 (1H, s).

Reference example 13

Synthesis of 8-methoxy-1-ethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

8-Methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (2.0 g) was dissolved in DMF (20 ml) and to the solution was added of 0.43 g of sodium hydride (60% in oil) under ice cooling. After adding a mixture of paramesh the Wali at room temperature until cessation of hydrogen evolution. The resulting mixture was again cooled in a water bath with ice, was added dropwise 1.2 ml of ethyliodide and the mixture was stirred at room temperature for 8 hours. The reaction mixture was poured into cooled with ice water, hydrochloric acid, was extracted with methylene chloride and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel to obtain 2.1 g (yield: 91%) of 8-methoxy-1-ethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde.

1H-NMR (CDCl3) δ ppm: to 1.15 (3H, t, J=7,1 Hz), of 2.51 (2H, t, J=7,0 Hz)to 3.36 (2H, t, J=7.0 Hz), of 3.97 (3H, s)to 4.01 (2H, t, J=7.4 Hz), 6,98 (1H, d, J=8.6 Hz), 7,60 (1H, d, J=8.6 Hz), 10,06 (1H, s).

Reference example 14

Synthesis of 8-methoxy-1-methyl-3,4-dihydro-1H-quinoline-2-it

8-Methoxy-3,4-dihydro-1H-quinoline-2-it (15 g) was dissolved in DMF (150 ml) and to the solution was added 3.6 g of sodium hydride (60% in oil) under ice cooling. After the addition the mixture was stirred at room temperature until cessation of hydrogen evolution. The resulting mixture was again cooled with ice water was added dropwise 5.8 ml under the conditions, followed by stirring at room temperature over night. Drove the solvent under reduced pressure and the residue was purified by chromatography on a column of silica gel to obtain 16.7 g (yield: 96%) of 8-methoxy-1-methyl-3,4-dihydro-1H-shall inolin-2-it.

1H-NMR (CDCl3) δ ppm: 2,5-2,6 (2H, m), 2,8-2,9 (2H, m), 3,39 (3H, s), 3,85 (3H, s), 6.75 in-6,9 (2H, m), 7,0-7,05 (1H, m).

Reference example 15

Synthesis of 8-methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

8-Methoxy-1-methyl-3,4-dihydro-1H-quinoline-2-she (1.5 g) was dissolved in dichloromethane (15 ml) and to the solution was added dichlorodimethyl ether (0,86 ml) at room temperature and then cooled with ice water. Was added dropwise a titanium tetrachloride (10.5 ml) and the resulting mixture was stirred at room temperature overnight. Then added dichlorodimethyl ether (1,29 ml) and titanium tetrachloride (15,8 ml) and the mixture was stirred at room temperature for 5 hours. The reaction mixture was poured into ice water and the aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. To the residue was added hexane, and the obtained insoluble substance was separated by filtration and dried to obtain of 1.37 g (yield: 80%) of 8-methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde.

1H-NMR (CDCl3) δ ppm: a 2.5 to 2.55 (2H, m), 3,3-of 3.45 (2H, m), of 3.96 (3H, s), of 6.99 (1H, d, J=8.6 Hz), 7,60 (1H, d, J=8.6 Hz), 10,06 (1H, s).

Reference example 16

Synthesis of 1-(4-biphenylyl)-6-bromo-3,4-dihydro-1H-quinoline-2-it

Sodium hydride (60% in oil) (0,49 g) was added at 0°C to a DMF solution (20 ml) of 6-bromo-3,4-dig the DRO-1H-quinoline-2-it (2,54 g), followed by stirring for 30 minutes. Added 4-bromomethylbiphenyl (3,05 g) and the resulting mixture was stirred at room temperature overnight. To the reaction mixture was added ice water, extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:6→1:2). The purified product was recrystallized from a mixed solvent of chloroform-diisopropyl ether to obtain 4,06 g (yield: 92%) of 1-(4-biphenylyl)-6-bromo-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

1H-NMR (DMSO-d6) δ ppm: 2,65-2,78 (2H, m), 2,89-3,03 (2H, m)to 5.17 (2H, s), make 6.90 (1H, d, J=8.7 Hz), 7.23 percent-7,39 (4H, m), 7,39-to 7.50 (3H, m), 7,50-7,71 (4H, m).

Reference example 17

Synthesis of 1-(4-biphenylyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-carboxaldehyde

DMF solution (30 ml) of 1-(4-biphenylyl)-6-bromo-3,4-dihydro-1H-quinoline-2-it (2,80 g), sodium formate (0,171 g) and bestafootballahand (0.25 g) was stirred in an atmosphere of carbon monoxide at 100°C for 4 hours. To the reaction mixture was added ice water, extracted with ethyl acetate and the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:4→1:2). The purified product was recrystallized from a mixed solvent of chloroform-diethyl-the first broadcast from the receipt of 1.95 g (yield: 78%) of 1-(4-biphenylyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-carboxaldehyde in the form of a white powder.

1H-NMR (DMSO-d6) δ ppm: 2,78 (2H, t, J=8.0 Hz), of 3.07 (2H, t, J=8.0 Hz), of 5.24 (2H, s), to 7.15 (1H, d, J=8,4 Hz), 7,25-7,49 (5H, m), 7,55-of 7.82 (6H, m), 9,84 (1H, s).

Reference example 18

Synthesis of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-carboxaldehyde

Sodium hydride (60% in oil) (1.3 g) was added at 0°C to a DMF solution (50 ml) of 2-oxo-1,2-dihydroquinoline-4-carboxaldehyde (5,13 g), followed by stirring for 30 minutes. Added 4-Chlorobenzilate (7.0 g) and the resulting mixture was stirred at room temperature overnight. To the reaction mixture was added ice water, extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:10→1:4). The purified product was recrystallized from a mixed solvent of chloroform-diisopropyl ether-n-hexane to obtain 4,13 g (yield: 47%) of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-carboxaldehyde in the form of a white powder.

1H-NMR (DMSO-d6) δ ppm: of 5.55 (2H, s), from 7.24 (2H, d, J=8.5 Hz), 7,28-7,39 (4H, m), 7,45 (1H, d, J=8,4 Hz), 7,50-to 7.64 (1H, m), 8,68 (1H, DD, J=1,3, 8.1 Hz), 10,24 (1H, s).

Reference example 19

Synthesis of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxaldehyde

Sodium hydride (60% in oil) (1.3 g) was added at 0°C to a DMF solution (50 ml) of 2-oxo-1,2-dihydroquinoline-3-carboxaldehyde (5,13 g) with subsequent displacement is ywaniem within 30 minutes. Added 4-Chlorobenzyl bromide (7.0 g) and the resulting mixture was stirred at room temperature overnight. To the reaction mixture was added ice water, extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:10→1:4). The purified product was recrystallized from a mixed solvent of chloroform-diisopropyl ether to obtain to 6.57 g (yield: 72%) of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxaldehyde in the form of a white powder.

H-NMR (DMSO-d6) δ ppm: 5.56mm (2H, s), 7,21-7,39 (5H, m), 7,44 (1H, d, J=8.6 Hz), to 7.61-7,72 (1H, m), 8,02 (1H, DD, J=1,4, and 7.8 Hz), 8,59 (1H, s), 10,31 (1H, s).

Reference example 20

Synthesis of 5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it

Pyridine (30 ml) and triftormetilfullerenov anhydride (25 g) was added under stirring at 0°C to anhydrous dichloromethane solution (200 ml) of 5-hydroxy-3,4-dihydro-1H-quinoline-2-it (15.9 g), followed by stirring for 2 hours. The resulting mixture was concentrated under reduced pressure, to the residue was added water and was extracted with dichloromethane. The extract was washed with water, aqueous solution of potassium hydrosulfate and water in that order and dried over anhydrous sodium sulfate. After concentration under reduced pressure the residue paracrystal isofemale from a mixed solvent of ethyl acetate-diisopropyl ether to obtain 28 g (yield: 97%) of 5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it is in the form of a light brown powder.

1H-NMR (CDCl3) δ ppm: to 2.67 (2H, DD, J=6.3 Hz, J=8,8 Hz), of 3.07 (2H, t, J=7.2 Hz), 6,80-of 6.90 (1H, m), 6.90 to-7,02 (1H, m), 7,16-to 7.32 (1H, m), of 8.95 (1H, users).

Reference example 21

Synthesis of 5-cyano-3,4-dihydro-1H-quinoline-2-it

5-Tripterocalyx-3,4-dihydro-1H-quinoline-2-she (1.5 g), cyanide zinc (1.3 g) and tetrakis(triphenylphosphine)palladium (0,59 g) suspended in DMF (20 ml) and the suspension was stirred at 100°C for 2 hours. The insoluble substance was filtered and to the filtrate was added ethyl acetate, followed by washing with water. The resulting mixture was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and the residue was recrystallized from a mixed solvent of ethyl acetate-diethyl ether to obtain 0.71 g (yield: 81%) of 5-cyano-3,4-dihydro-1H-quinoline-2-it is in the form of a light brown powder.

1H-NMR (DMSO-d6) δ ppm: 2,45-2,60 (2H, m), 3,05 (2H, t, J=7.2 Hz), 7,08-to 7.18 (1H, m), 7,28-7,40 (2H, m), 10,37 (1H, users).

Reference example 22

Synthesis of 2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

5-Cyano-3,4-dihydro-1H-quinoline-2-he (100 mg) and Raney Nickel (100 mg) suspended in formic acid (10 ml) and the suspension is boiled under reflux for 2 hours. Was added 100 mg of Raney Nickel, followed by boiling under reflux for 1 hour. The reaction mixture was filtered to remove insoluble materials and the filtrate conc who was narrowly. To the residue was added ethyl acetate and water, and after mixing, the mixture was filtered through Celite. The filtrate was divided into layers, the organic layer was washed with water and dried over anhydrous sodium sulfate. After concentration under reduced pressure the residue was recrystallized from a mixed solvent of ethyl acetate-n-hexane to obtain 77 mg (yield: 76%) of 2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a light brown powder.

1H-NMR (DMSO-d6) δ ppm: 2,39 is 2.51 (2H, m)to 3.35 (2H, t, J=7.4 Hz), 7,10-7,17 (1H, m), 7,31-7,41 (1H, m), 7,44 is 7.50 (1H, m), 10,18 (1H, s), 10,26 (1H, users).

Reference example 23

Synthesis of 1-(4-biphenylyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

Sodium hydride (60% in oil) (0.25 g) was added at 0°C to a DMF solution (10 ml) of 2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (1.0 g), followed by stirring for 30 minutes. Added 4-bromomethylbiphenyl (1,69 g) and the resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added water and was extracted with ethyl acetate. The extract was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:4→1:2). The purified product was recrystallized from a mixed solvent chloropropiophenone ether with the receipt of 1.11 g (yield: 56%) of 1-(4-biphenylyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of colorless plate crystals.

1H-NMR (DMSO-d6) δ ppm: 2,65-2,78 (2H, m), of 3.45 (2H, t, J=7,6 Hz), of 5.24 (2H, s), 7,21-7,49 (7H, m), 7,49-EUR 7.57 (1H, m), EUR 7.57-of 7.70 (4H, m), 10,24 (1H, s).

Reference example 24

Synthesis of 5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-it

8-Methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (42 g) suspended in toluene (400 ml)to the suspension was added ethylene glycol (33,7 ml) and the monohydrate p-toluensulfonate acid (0,78 g) and the resulting mixture was boiled under reflux in an apparatus of the Dean-stark for 4.5 hours. The reaction mixture was cooled and added 10 ml of an aqueous solution containing 1,72 g of sodium bicarbonate. For some time the mixture was mixed, and the resulting solid substance was separated by filtration. The solid is washed with water and toluene and dried at 60°C to obtain 35.5 g (yield: 70%) of 5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-it is in the form of white crystals.

1H-NMR (DMSO-d6) δ ppm: 2,33 is 2.44 (2H, m), 2,85 are 2.98 (2H, m), with 3.79 (3H, s), 3,86-4,08 (4H, m), 5,78 (1H, s)6,86 (1H, d, J=8.5 Hz), 7,07 (1H, d, J=8.5 Hz), 8,97 (1H, s).

Reference example 25

Synthesis of 1-(6-chloropyridin-3-ylmethyl)-5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-it

Sodium hydride (55% in oil) (2.1 g) was added in small portions under ice cooling to a DMF solution (70 ml) of 5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-it (10 g) and the mixture was stirred at room temperature until PR is the reduction of hydrogen. The resulting mixture was again cooled with ice and added dropwise DMF solution (30 ml) of 2-chloro-5-chloromethylpyridine (9,74 g). After stirring at room temperature for 4 hours, the reaction mixture was poured into ice water and the resulting insoluble matter was separated by filtration. The solid is washed with water and diethyl ether and dried to obtain 11,84 g (yield: 79%) of 1-(6-chloropyridin-3-ylmethyl)-5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-it is in the form of a light yellow solid.

1H-NMR (DMSO-d6) δ ppm: 2,47 of $ 2.53 (2H, m), 2,88-to 2.94 (2H, m), 3,63 (3H, s), 3,91-Android 4.04 (4H, m), to 5.08 (2H, s)5,80 (1H, s), to 6.88 (1H, d, J=8.6 Hz), 7,19 (1H, d, J=8.6 Hz), 7,38 (1H, d, J=8,3 Hz), 7,60 (1H, DD, J1=2.3 Hz, J2=8,3 Hz), 8,19 (1H, d, J=2.3 Hz).

Reference example 26

Synthesis of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-[6-(N-methyl-N-phenylamino)pyridine-3-ylmethyl]-3,4-dihydro-1H-quinoline-2-it

1-(6-Chloropyridin-3-ylmethyl)-5-[1,3]dioxolane-2-yl-8-methoxy-3,4-dihydro-1H-quinoline-2-he (0.4 g), Tris(dibenzylideneacetone)dipalladium (48,8 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (92,6 mg) and tert-piperonyl sodium (0.15 g) suspended in toluene (10,6 ml). Was added N-methylaniline (0.17 g) and the resulting mixture was boiled under reflux in an argon atmosphere for 13 hours. After concentration under reduced pressure the residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:1→dihormati is:methanol=20:1). The purified product was concentrated under reduced pressure to obtain 0.45 g (yield: 95%) of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-[6-(N-methyl-N-phenylamino)pyridine-3-ylmethyl]-3,4-dihydro-1H-quinoline-2-it is in the form of an amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,52-of 2.58 (2H, m), 2,74 is 2.80 (2H, m), 3,40 (3H, s), 3,83 (3H, s), 3,98-4,12 (4H, m), with 5.22 (2H, s), of 5.81 (1H, s), to 6.39 (1H, d, J=8.7 Hz), 6,76 (1H, d, J=8.7 Hz), 7,13-7,26 (4H, m), 7,33-7,39 (3H, m), to 7.99 (1H, d, J=2.0 Hz).

Reference example 27

Synthesis of 8-methoxy-1-[6-(N-methyl-N-phenylamino)pyridine-3-ylmethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

p-Toluensulfonate pyridinium (PPTS) (0.54 g) was added to a mixed solution of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-[6-(N-methyl-N-phenylamino)pyridine-3-ylmethyl]-3,4-dihydro-1H-quinoline-2-she (0.95 g) in acetone (19 ml) and water (9.5 ml), followed by boiling under reflux for 2 hours. To the reaction mixture were added an aqueous solution of sodium bicarbonate and was extracted with ethyl acetate. The extract was washed twice with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:1). The purified product was concentrated under reduced pressure to get to 0.69 g (yield: 81%) of 8-methoxy-1-[6-(N-methyl-N-phenylamino)pyridine-3-ylmethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-Carbo is zaldehyde in the form of a light yellow amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,53 at 2.59 (2H, m), 3,28-to 3.34 (2H, m), 3,39 (3H, s), of 3.95 (3H, s), 5,23 (2H, s), 6,37 (1H, d, J=8,8 Hz), make 6.90 (1H, d, J=8.6 Hz), to 7.09 (1H, DD, J1=2.4 Hz, J2=8,8 Hz), 7,16-7,21 (3H, m), 7,33-7,39 (2H, m), 7,54 (1H, d, J=8.6 Hz), 7,94 (1H, d, J=2.4 Hz), 10,00 (1H, s).

Reference example 28

Synthesis of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-(6-thiophene-3-espiridion-3-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

1-(6-Chloropyridin-3-ylmethyl)-5-(1,3-dioxolane-2-yl)-8-methoxy-3,4-dihydro-1H-quinoline-2-he (0.4 g), tetrakis(triphenylphosphine)palladium (0.12 g) and 2n. an aqueous solution of sodium carbonate (2.5 ml) added 8 ml of 1,2-dimethoxyethane and was added 0.20 g of 3-tiefenbronn acid followed by boiling under reflux in an argon atmosphere for 4 hours. To the reaction mixture was added water and was extracted with ethyl acetate. The extract was washed twice with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:1). The purified product was concentrated under reduced pressure to obtain 0.45 g (yield: 95%) of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-(6-thiophene-3-espiridion-3-ylmethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of a light brown amorphous solid.

1H-NMR (DMSO-d6) δ ppm: 2,49 is 2.51 (2H, m), 2,89-only 2.91 (2H, m), 3,71 (3H, s), 3,91-Android 4.04 (4H, m), 5,19 (2H, s), 5,79 (1H, s), 6.87 in (1H, d, J=8 Hz), 7,16 (1H, d, J=8,8 Hz), 7,51-7,74 (4H, m), 8,09-8,10 (1H, m), 8,32 (1H, d, J=2.0 Hz).

Reference example 29

Synthesis of 8-methoxy-1-(6-thiophene-3-espiridion-3-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

p-Toluensulfonate pyridinium (PPTS) (0.24 g) was added to a mixed solution of 5-(1,3-dioxolane-2-yl)-8-methoxy-1-(6-thiophene-3-espiridion-3-ylmethyl)-3,4-dihydro-1H-quinoline-2-she (0.4 g) in acetone (8 ml) and water (4 ml), followed by boiling under reflux for 1.5 hours. The resulting mixture was concentrated under reduced pressure, extracted with dichloromethane, washed with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain 0.4 g (yield: quantitative) of 8-methoxy-1-(6-thiophene-3-espiridion-3-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a light brown amorphous solid.

1H-NMR (DMSO-d6) δ ppm: of 2.51-of 2.58 (2H, m), 3,34-to 3.41 (2H, m), 3,81 (3H, s), 5,19 (2H, s), to 7.09 (1H, d, J=8,8 Hz), 7,54-7,74 (5H, m), 8,09-8,10 (1H, m), 8,35 (1H, d, J=1,8 Hz), there is a 10.03 (1H, s).

Reference example 30

Synthesis of 5-(1,3-dioxolane-2-yl)-1-phenyl-3,4-dihydro-1H-quinoline-2-it

5-(1,3-Dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (2.30 g, 10.5 mmol), iadanza (3.5 ml, to 31.5 mmol), copper iodide(I) (400 mg, 2.10 mmol), TRANS-1,2-diaminocyclohexane (0,129 ml, 1.05 mmol) and cesium carbonate (6,84 g, 21,0 mmol) was stirred in 30 ml of 1,4-dioxane by copaceni the under reflux for three days. After cooling, the insoluble substance was filtered through a loose layer of Celite. To the filtrate was added ethyl acetate and water and the resulting mixture was washed twice with water and once with saturated sodium chloride solution), dried (MgSO4) and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:3→1:1) to obtain only 2.91 g (yield: 92%) of 5-(1,3-dioxolane-2-yl)-1-phenyl-3,4-dihydro-1H-quinoline-2-it is in the form of a white solid.

1H-NMR (CDCl3) δ ppm: 2,75-2,90 (2H, m), 3,11-of 3.27 (2H, m), 3,98-of 4.25 (4H, m), of 5.99 (1H, s), to 6.39 (1H, d, J=7,6 Hz), 7,05 (1H, t, J=8.0 Hz), 7,16-7,30 (3H, m), 7,35-7,56 (3H, m).

Reference example 31

Synthesis of 1-phenyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

2n. Hydrochloric acid (5 ml) was added to a solution of 5-(1,3-dioxolane-2-yl)-1-phenyl-3,4-dihydro-1H-quinoline-2-it (2,60 g) in THF (30 ml) followed by stirring at room temperature over night. After distillation THF under reduced pressure was added ethyl acetate and water and the resulting mixture was washed twice with water and once with saturated sodium chloride solution), dried (MgSO4) and concentrated under reduced pressure. The obtained solid substance was recrystallized from a mixture of chloroform-diethyl ether to obtain of 1.93 g (yield: 87%) of 1-phenyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a beige powder is.

1H-NMR (CDCl3) δ ppm: 2,75-2,89 (2H, m), 3,53-3,68 (2H, m), of 6.65 (1H, DD, J=0.9 Hz, J=8,2 Hz), 7,15-7,20 (3H, m), 7,39-to 7.61 (4H, m), 10,24 (1H, s).

Reference example 32

Synthesis of 5-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-8-carboxaldehyde

5-Methoxy-3,4-dihydro-1H-quinoline-2-he (5,00 g, 26 mmol) was dissolved in dichloromethane (100 ml) and to the solution was added dichlorodimethyl ether (7.65 ml, 85 mmol) at 0°C. was Added dropwise a titanium tetrachloride (12,4 ml, 113 mmol) at a temperature of not higher than 10°C. the Mixture was stirred at room temperature for 2 hours, the reaction mixture was poured into ice water and separated into layers. The aqueous layer was extracted with dichloromethane. The organic layers were combined and washed twice with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane, was added diethyl ether and the resulting insoluble matter was separated by filtration and dried to obtain 5.32 g (yield: 92%) of 5-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-8-carboxaldehyde in the form of a light brown powder.

1H-NMR (CDCl3) δ ppm: 2,55-to 2.67 (2H, m), 2,90 totaling 3.04 (2H, m), of 3.94 (3H, s), 6,69 (1H, d, J=8.6 Hz), 7,53 (1H, d, J=8.6 Hz), 9,79 (1H, s), or 10.60 (1H, users).

Reference example 33

Synthesis of 5-methoxy-8-methyl-3,4-dihydro-1H-quinoline-2-it

5-Methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-8-carboxaldehyde (1,00 g) and 1% palladium on carbon (100 mg) was added to a mixed solvent of acetic acid (10 ml) and ethanol (10 ml) followed by catalytic regeneration at 50°C for 1 hour. The catalyst was filtered and the filtrate was concentrated under reduced pressure. The residue was extracted with ethyl acetate and the extract was washed twice with water, a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-diethyl ether to obtain 826 mg (yield: 89%) of 5-methoxy-8-methyl-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

1H-NMR (CDCl3) δ ppm: 2,04 (3H, s), 2,54-to 2.65 (2H, m), 2,89-to 3.02 (2H, m), 3,81 (3H, s), 6,51 (1H, d, J=8,4 Hz), 6,97 (1H, d, J=8,4 Hz), 7,37 (1H, users).

Reference example 34

Synthesis of 5-hydroxy-8-methyl-3,4-dihydro-1H-quinoline-2-it

2n. Dichloromethane solution (52 ml) tribromide boron was added dropwise at -20°C to dichloromethane solution (100 ml) of 5-methoxy-8-methyl-3,4-dihydro-1H-quinoline-2-she (10.0 g). After stirring for 1 hour the reaction mixture was poured into ice water and separated into layers. The organic layer was washed twice with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-diethyl ether to obtain 9.4 g (yield: quantitative) 5-hydroxy-8-methyl-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

1H-NMR (CDCl3) δ..: 2,14 (3H, C)2,60-to 2.65 (2H, m), 2,94-to 2.99 (2H, m), of 5.50 (1H, users), of 6.45 (1H, d, J=8,2 Hz), to 6.88 (1H, d, J=8,2 Hz), 7,40 (1H, users).

Reference example 35

Synthesis of 8-methyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it

Pyridine (6.2 ml) and triftormetilfullerenov anhydride (10.3 ml) was added under stirring at 0°C to anhydrous dichloromethane solution (30 ml) of 5-hydroxy-8-methyl-3,4-dihydro-1H-quinoline-2-she (9.0 g), followed by stirring for 1 hour. The resulting mixture was concentrated under reduced pressure, to the residue was added water and was extracted with dichloromethane. The extract was washed with water, aqueous solution of potassium hydrosulfate and water in that order and dried over anhydrous sodium sulfate. After concentration under reduced pressure the residue was recrystallized from a mixed solvent of ethyl acetate-diisopropyl ether to obtain 28 g (yield: 97%) of 8-methyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it is in the form of a light brown powder.

1H-NMR (CDCl3) δ ppm: of 2.26 (3H, s), 2,60-by 2.73 (2H, m), 2,99-of 3.12 (2H, m), 6.89 in (1H, d, J=8.5 Hz), 7,11 (1H, d, J=8.5 Hz), to 7.67 (1H, users).

Reference example 36

Synthesis of 5-cyano-8-methyl-3,4-dihydro-1H-quinoline-2-it

8-Methyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-he (4.0 g), cyanide zinc (3,34 g) and tetrakis(triphenylphosphine)palladium (0,299 g) suspended in DMF (40 ml) and the suspension was stirred at 100°C for hours. The insoluble substance was filtered and to the filtrate was added ethyl acetate, followed by washing with water. After drying over anhydrous magnesium sulfate dry product was concentrated and the residue was recrystallized from a mixed solvent of DMF-ethanol to obtain 2.1 g (yield: 87%) of 5-cyano-8-methyl-3,4-dihydro-1H-quinoline-2-it is in the form of a light brown powder.

1H-NMR (CDCl3) δ ppm: 2,31 (3H, s), 2,64 is 2.75 (2H, m), 3,15-of 3.27 (2H, m), 7,14 (1H, d, J=7.9 Hz), 7,24 (1H, d, J=7.9 Hz), to 7.67 (1H, users).

Reference example 37

Synthesis of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

5-Cyano-8-methyl-3,4-dihydro-1H-quinoline-2-he (2.0 g) and Raney Nickel (10 g) is suspended in formic acid (40 ml) and the suspension is boiled under reflux for 6 hours. The reaction mixture was filtered to remove insoluble materials and the filtrate was concentrated. To the residue was added ethyl acetate and water, and after mixing, the mixture was filtered through Celite. The filtrate was divided into layers, the organic layer was washed with water and dried over anhydrous sodium sulfate. After concentration under reduced pressure the residue was recrystallized from a mixed solvent of ethyl acetate-diethyl ether to obtain 1.29 g (yield: 62%) of 8-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a light brown powder.

1H-NMR (DMSO-d6) δ m is.: of 2.30 (3H, C)2,37-of 2.50 (2H, m), 3,28-of 3.43 (2H, m), 7,26 (1H, d, J=7.8 Hz), 7,44 (1H, d, J=7.8 Hz), of 9.56 (1H, s), 10,15 (1H, s).

Reference example 38

Synthesis of 5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it

8-Bromo-5-methoxy-3,4-dihydro-1H-quinoline-2-he (10.0 g), tetrakis(triphenylphosphine)palladium (0.45 g) and potassium carbonate (5.4 g) suspended in dioxane (100 ml) and was added phenylboronic acid (5,24 g), followed by boiling under reflux in an argon atmosphere for 2 hours. The reaction mixture was concentrated under reduced pressure, to the residue was added water and the resulting mixture was extracted with ethyl acetate. The extract was washed twice with water, washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-n-hexane to obtain of 8.3 g (yield: 84%) of 5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it is in the form of light yellow powder.

1H-NMR (CDCl3) δ ppm: 2.57 m-of 2.64 (2H, m), 2,97 totaling 3.04 (3H, m), 3,88 (2H, s), of 6.66 (1H, d, J=8.5 Hz), to 7.09 (1H, d, J=8.5 Hz), 7,27-7,52 (6H, m).

Reference example 39

Synthesis of 1-(biphenyl-4-ylmethyl)-5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it

Sodium hydride (60% in oil) (0.87 g) was added at 0°C to a DMF solution (50 ml) of 5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-she (5.0 g), followed by stirring for 30 minutes. Added 4-bromomethylbiphenyl (537 g) and the resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added water and was extracted with ethyl acetate. The extract was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:10→1:5). The purified product was recrystallized from a mixed solvent of ethyl acetate-n-hexane-diethyl ether to obtain 6.8 g (yield: 82%) of 1-(biphenyl-4-ylmethyl)-5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

1H-NMR (CDCl3) δ ppm: 2,64-2,70 (2H, m), 2,84-2,96 (2H, m), 3,86 (3H, s), of 4.49 (2H, s), of 6.73 (1H, d, J=8.6 Hz), 6,91 (2H, d, J=8.1 Hz), 7,13 (1H, d, J=8.6 Hz), 7.24 to at 7.55 (12H, m).

Reference example 40

Synthesis of 1-(biphenyl-4-ylmethyl)-5-hydroxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it

Dichloromethane solution (12 ml) 2n. tribromide boron was added dropwise at -20°C to dichloromethane solution (50 ml) of 1-(biphenyl-4-ylmethyl)-5-methoxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it (5,00 g). After stirring for 4 hours the reaction mixture was poured into ice water and separated into layers. The organic layer was washed twice with water, washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of dichloromethane-diisopropyl ether to obtain 5,01 g (yield quantitative) 1-(biphenyl-4-ylmethyl)-5-hydroxy-8-phenyl-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

1H-NMR (CDCl3) δ ppm: 2,66-to 2.74 (2H, m), 2,84-2,90 (2H, m), 4,48 (2H, s), of 5.84 (1H, users), is 6.61 (1H, d, J=8,4 Hz), 6,92 (2H, d, J=8,2 Hz), 7,01 (1H, d, J=8,4 Hz), 7,22-7,54 (12H, m).

Reference example 41

Synthesis of 1-(biphenyl-4-ylmethyl)-8-phenyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it

Pyridine (1,12 ml) and triftormetilfullerenov anhydride (1,99 ml) was added under stirring at 0°C to anhydrous dichloromethane solution (40 ml) of 1-(biphenyl-4-ylmethyl)-5-hydroxy-8-phenyl-3,4-dihydro-1H-quinoline-2-she (4.0 g), followed by stirring for 1 hour. The resulting mixture was concentrated under reduced pressure, to the residue was added water and was extracted with dichloromethane. The extract was washed with water, aqueous solution of potassium hydrosulfate and water in order, dried over anhydrous sodium sulfate and concentrated under reduced pressure to get the 5.45 g (yield: quantitative) of 1-(biphenyl-4-ylmethyl)-8-phenyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-it is in the form of a white amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,67-of 2.81 (2H, m), 2,90-3,03 (2H, m), 4,48 (2H, s), 6,85 (2H, d, J=8,2 Hz), 7,05-to 7.15 (1H, m), 7,20-7,58 (13H, m).

Reference example 42

Synthesis of 1-(biphenyl-4-ylmethyl)-5-cyano-8-phenyl-3,4-dihydro-1H-quinoline-2-it

1-(Biphenyl-4-ylmethyl)-8-phenyl-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-he (5,2 g), cyanide zinc (2.50 g) and tetrakis(triphenylphosphine)palladium (0,224 g) WM who was enduropale in DMF (50 ml) followed by stirring at 100°C for 4 hours. The insoluble substance was filtered and to the filtrate was added ethyl acetate and the mixture washed with water. After drying over anhydrous magnesium sulfate dry product was concentrated to obtain 2.1 g (yield: 90%) of 1-(biphenyl-4-ylmethyl)-5-cyano-8-phenyl-3,4-dihydro-1H-quinoline-2-it is in the form of a white amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,75-2,82 (2H, m), 3,09 is 3.15 (2H, m), 4,48 (2H, s), 6,85 (2H, d, J=8,3 Hz), 7,20-EUR 7.57 (14H, m).

Reference example 43

Synthesis of 1-(biphenyl-4-ylmethyl)-8-phenyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

1-(Biphenyl-4-ylmethyl)-5-cyano-8-phenyl-3,4-dihydro-1H-quinoline-2-he (3.0 g) and Raney Nickel (15 g) suspended in formic acid (60 ml) and the suspension is boiled under reflux for 11 hours. The reaction mixture was filtered to remove insoluble materials and the filtrate was concentrated. To the residue was added ethyl acetate and water, and after mixing, the mixture was filtered through Celite. The filtrate was divided into layers and the organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:10→1:3). The purified product was concentrated with the receipt of 0.44 g (yield: 15%) 1-(biphenyl-4-ylmethyl)-8-phenyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a white amorphous solid matter what.

1H-NMR (CDCl3) δ ppm: 2,69-of 2.75 (2H, m), 2,37 is 2.43 (2H, m), 4,48 (2H, s), 6.87 in (2H, d, J=8,3 Hz), 7,25-of 7.55 (13H, m), to 7.61 (1H, d, J=8.0 Hz), and 10.20 (1H, s).

Reference example 44

Synthesis of 1-benzyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

Sodium hydride (60% in oil) (1.07 g) was added at 0°C to a DMF solution (50 ml) of 8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (5.0 g), followed by stirring for 30 minutes. Added benzylbromide (3,47 ml) and the resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added water and was extracted with ethyl acetate. The extract was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-n-hexane to obtain 6.6 g (yield: 92%) of 1-benzyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a white powder.

1H-NMR (CDCl3) δ ppm: 2,60 (2H, t, J=7.0 Hz), to 3.38 (2H, t, J=7.0 Hz), 3,82 (3H, s), from 5.29 (2H, s), PC 6.82 (1H, d, J=8.6 Hz), 7,0 is 7.3 (5H, m), and 7.5 (1H, d, J=8.6 Hz), 10,00 (1H, s).

Reference example 45

Synthesis of 1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

1-Benzyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (3.0 g) and 4-methylbenzoyl sodium (3,27 g) was added to DMSO (30 ml) followed by stirring at 100°C in accordance with the definition in 40 minutes. Was added to the reaction mixture water and an aqueous solution of potassium hydrosulfate was added and was extracted with ethyl acetate. The extract was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-n-hexane to obtain 6.6 g (yield: 92%) of 1-benzyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a light brown powder.

1H-NMR (DMSO-d6) δ ppm: 2,42 at 2.59 (2H, m), 3,19 is 3.40 (2H, m), 5,31 (2H, s), 6,85 (1H, d, J=8.5 Hz), 7,05-7,27 (5H, m), the 7.43 (1H, d, J=8.5 Hz), 9,94 (1H, s), 11,12 (1H, s).

Reference example 46

Synthesis of 1-(4-carbomethoxyamino)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

Sodium hydride (60% in oil) (2,87 g) was added at 0°C to a DMF solution (100 ml) of 8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde (13,4 g), followed by stirring for 30 minutes. Was added methyl 4-bromoethylene (18.0 g) and the resulting mixture was stirred at room temperature overnight. To the reaction mixture was added water and was extracted with ethyl acetate. The extract was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (ethyl acetate:n-hexane=1:4→1:2). Cleared about the SPS recrystallized from a mixed solvent of chloroform-diisopropyl ether to obtain 14,43 g (yield: 62%) of 1-(4-carbomethoxyamino)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a white powder.

1H-NMR (DMSO-d6) δ ppm: 2,50-2,61 (2H, m), 3,29-to 3.41 (2H, m), 3,71 (3H, s), with 3.79 (3H, s), is 5.18 (2H, s), 7,06 (1H, d, J=8.7 Hz), 7,25 (2H, d, J=8,2 Hz), 7,60 (1H, d, J=8.7 Hz), 7,81 (2H, d, J=8,2 Hz), 10,02 (1H, s).

Using the appropriate source materials and following the method of reference example 41 was synthesized compounds of reference examples 47-50.

Reference example 47

8-Chloro-5-tripterocalyx-3,4-dihydro-1H-quinoline-2-he

1H-NMR (CDCl3) δ ppm: 2,63-of 2.75 (2H, m), 3,02 is 3.15 (2H, m)6,94 (1H, d, J=8,9 Hz), 7,34 (1H, d, J=8,9 Hz), the 7.85 (1H, users).

Reference example 48

6 Tripterocalyx-3,4-dihydro-1H-quinoline-2-he

1H-NMR (CDCl3) δ ppm: 2,60-by 2.73 (2H, m), a 3.01 (2H, t, J=8.0 Hz), for 6.81-6,92 (1H, m), 7,00 for 7.12 (2H, m), which is 9.09 (1H, users).

Reference example 49

7 Tripterocalyx-3,4-dihydro-1H-quinoline-2-he

1H-NMR (CDCl3) δ ppm: 2,60-a 2.71 (2H, m)of 3.00 (2H, t, J=8.0 Hz), 6,70-6,77 (1H, m), 6,84-to 6.95 (1H, m), 7,16-7,30 (1H, m), 8,80 (1H, users).

Reference example 50

8 Tripterocalyx-3,4-dihydro-1H-quinoline-2-he

1H-NMR (CDCl3) δ ppm: 2,63-of 2.75 (2H, m), 3,05 (2H, t, J=7.9 Hz), 7,03 (1H, t, J=7.9 Hz), 7,12-7,28 (2H, m), 7,78 (1H, users).

Reference example 51

Synthesis of 6-oxo-5,6-dihydropteridine-2-carbonitrile

Ethyl ester of 2-(4,4-dimethyl-[1,3,2]dioxaborolan-2-yl)benzoic acid (19,84 g), 2-iodine-4-cyanoaniline (18,47 g), tetrakis(triphenylphosphine)palladium (8,75 g) and potassium phosphate (up RUB 35.36 g) were added to dioxane (360 ml) and the resulting mixture is boiling the or under reflux overnight. The reaction solution was cooled and the resulting solid substance was separated by filtration, washed with water and dried to obtain 17.3 g (yield: quantitative) specified in the title compound as a yellow solid.

1H-NMR (DMSO-d6) δ ppm: 7,47 (1H, d, J=8.5 Hz), about 7.6 to 8.0 (3H, m), of 8.1 to 8.2 (1H, m), 8,3 an 8.4 (1H, m), 8,98 (1H, s), a 12.05 (1H, users).

Reference example 52

Synthesis of 5-benzyl-6-oxo-5,6-dihydropteridine-2-carbonitrile

6-Oxo-5,6-dihydropteridine-2-carbonitrile (1 g) suspended in DMF (20 ml)was added 60% sodium hydride (0.2 g) under ice cooling and the mixture was stirred until cessation of hydrogen evolution. Added benzylbromide (0,59 ml) followed by stirring at room temperature for 1 hour. Added water and the resulting solid substance was separated by filtration and was purified by chromatography on silica gel (dichloromethane:n-hexane=1:1) to obtain 0.68 g (yield: 48%) indicated in the title compounds as colorless crystals.

1H-NMR (DMSO-d6) δ ppm: to 5.57 (2H, s), 7,1-7,5 (6H, m), 7,6-of 7.95 (3H, m), of 8.27 (1H, d, J=8,3 Hz), 8,58 (1H, d, J=1,8 Hz), 8,63 (1H, DD, J=8,3 Hz, J=1.8 Hz).

Using the appropriate source materials and following the method of reference example 52 was synthesized compounds of reference examples 53-54.

Reference example 53

5-Ethyl-6-oxo-5,6-dihydropteridine-2-carbonitril

1H-NMR (DMSO-d6) δ ppm: USD 1.43 (3H, t, J=71 Hz), 4,47 (2H, t, J=7,1 Hz), 7,35 to 7.9 (4H, m), of 8.27 (1H, d, J=8,3 Hz), 8,5-8,65 (2H, m).

Reference example 54

5-(1-Biphenyl-4-ylmethyl)-6-oxo-5,6-dihydropteridine-2-carbonitril

1H-NMR (DMSO-d6) δ ppm: to 5.57 (2H, s), 7,1-7,5 (6H, m), 7,6-of 7.95 (3H, m), of 8.27 (1H, d, J=8,3 Hz), 8,58 (1H, d, J=1,8 Hz), 8,63 (1H, DD, J=8,3 Hz, J=1.8 Hz).

Reference example 55

Synthesis of 5-benzyl-6-oxo-5,6-dihydropteridine-2-carboxaldehyde

5-Benzyl-6-oxo-5,6-dihydropteridine-2-carbonitrile (1.24 g) and Raney Nickel (0.8 g) is suspended in 75% formic acid (25 ml). The suspension is boiled under reflux for 1 hour and 40 minutes and filtered hot. The filtrate was concentrated and purified by chromatography on silica gel (methylene chloride:methanol=50:1) to obtain 1.08 g (yield: 80%) indicated in the title compounds as colorless crystals.

1H-NMR (DMSO-d6) δ ppm: 5,69 (2H, s), 7,15-to 7.35 (6H, m), 7.5 to with 8.05 (3H, m), of 8.47 (1H, d, J=7.9 Hz), to 8.70 (1H, d, J=8.1 Hz), 8,63 (1H, d, J=1.4 Hz), 10,08 (1H, s).

Using the appropriate source materials and following the method of reference example 55, synthesized the compound of reference example 56.

Reference example 56

5-Ethyl-6-oxo-5,6-dihydropteridine-2-carboxaldehyde

1H-NMR (DMSO-d6) δ ppm: to 1.45 (3H, t, J=7,1 Hz), 4,50 (2H, t, J=7,1 Hz), 7,15-to 7.35 (6H, m), 7.5 to 8,15 (4H, m), 8,39 (1H, d, J=8.1 Hz), 8,56 (1H, DD, J=8,1 Hz, J=1.3 Hz), 8,81 (1H, d, J=1,8 Hz), 10,11 (1H, s).

Using the appropriate source materials and following the methodology with alonoso example 13, synthesized compounds of reference examples 104-130, 133, 134 and 137-141.

Using the appropriate source materials and following the method of reference example 19 was synthesized compounds of reference examples 147 and 148.

Using the appropriate source materials and following the method of reference example 21 was synthesized compounds of reference examples 57-63.

Using the appropriate source materials and following the method of reference example 23 was synthesized compounds of reference examples 144-145 and 152-156.

Using the appropriate source materials and following the method of reference example 24 was synthesized compounds of reference examples 70, 71 and 81.

Using the appropriate source materials and following the method of reference example 25 was synthesized compounds of reference examples 64-69, 72, 79, 80, 82, and 83.

Using the appropriate source materials and following the method of reference example 26 was synthesized compounds of reference examples 75-77.

Using the appropriate source materials and following the method of reference example 28 was synthesized compounds of reference examples 74 and 78.

Using the appropriate source materials and following the method of reference example 29 was synthesized compounds of reference examples 98, 99, 100-103, 131, 135, 136 and 146.

Using the appropriate source materials and following the method of reference example the and 31, synthesized compounds of reference examples 84-97 and 142.

Using the appropriate source materials and following the method of reference example 37 was synthesized compounds of reference examples 149-151.

Table 1-22 (see the end of the description).

In tables 1-22 Me means methyl and tBu means tert-butyl.

Reference example 158

Synthesis of 5-(1,3-dioxolane-2-yl)-1-{4-[(N-methyl-N-phenylamino)methyl]benzyl}-3,4-dihydro-1H-quinoline-2-it

1-(4-Chloromethylbenzene)-5-(1,3-dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (100 mg, 0.28 mmol), N-methylaniline (0,045 ml, 0.42 mmol) and potassium carbonate (57,9 mg, 0.42 mmol) were added to acetonitrile (1 ml), followed by boiling under reflux for 4 hours. After cooling to room temperature, to the reaction mixture was added water and was extracted with dichloromethane. The organic layer was washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. The dry product was concentrated under reduced pressure and the residue was purified preparative thin-layer chromatography on silica gel (n-hexane:ethyl acetate=1:1). The purified product was concentrated to dryness under reduced pressure to obtain 80 mg (yield: 67%) of 5-(1,3-dioxolane-2-yl)-1-{4-[(N-methyl-N-phenylamino)methyl]benzyl}-3,4-dihydro-1H-quinoline-2-it is in the form of a light yellow amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,72-2,78 (2H, m), 2,98 (3, C)is 3.08-of 3.12 (2H, m), 4,06-4,16 (4H, m), 4,48 (2H, s), of 5.15 (2H, s)5,94 (1H, s), 6,67-6,74 (3H, m), 6.90 to (1H, d, J=8.1 Hz), 7,09-7,26 (8H, m).

Reference example 159

Synthesis of 5-(1,3-dioxolane-2-yl)-1-(6-piperidinomethyl-2-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

1-(6-Chloromethylpyridine-2-ylmethyl)-5-(1,3-dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (1.0 g, 2.8 mmol) was added to piperidine (2 ml), followed by stirring in an argon atmosphere at 100°C for 2 hours. After cooling to room temperature, to the reaction mixture were added water and a small amount of acetic acid and was extracted with ethyl acetate twice. The organic layers were combined, washed twice with water and once with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The dry product was concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=20:1). The purified product was concentrated to dryness under reduced pressure to obtain 0.73 g (yield: 64%) of 5-(1,3-dioxolane-2-yl)-1-(6-piperidinomethyl-2-ylmethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of a light yellow amorphous solid.

1H-NMR (CDCl3) δ ppm: 1,44-1,49 (2H, m), 1.56 to of 1.65 (4H, m), 2,42 is 2.46 (4H, m), 2,74 is 2.80 (2H, m), 3,09 is 3.15 (2H, m)to 3.64 (2H, s), 4,01-4,17 (4H, m), 5,27 (2H, s), 5,95 (1H, s), 6,95-7,02 (2H, m), 7,11 (1H, t, J=7.9 Hz), of 7.23-7,31 (2H, m), 7,54 (1H, t, J=7,7 Hz).

Reference example 160

Synthesis of 5-(1,3-dioxolane-2-yl)-1-(4-phenylsulfanyl ensil)-3,4-dihydro-1H-quinoline-2-it

1-(4-Chloromethylbenzene)-5-(1,3-dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (1.0 g, and 2.79 mmol), thiophenol (0,37 ml, 3.63 mmol) and 1,8-diazabicyclo[5,4,0]undecene-7 (DBU) (0,84 ml, 5,59 mmol) was added to THF (30 ml), followed by boiling under reflux for 7 hours. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=1:1). The purified product was concentrated to dryness under reduced pressure to obtain 1.13 g (yield: 94%) of 5-(1,3-dioxolane-2-yl)-1-(4-phenylsulfanyl)-3,4-dihydro-1H-quinoline-2-it is in the form of a white solid.

1H-NMR (CDCl3) δ ppm: 2,73-and 2.79 (2H, m), 3,06-of 3.12 (2H, m), 4,01-4,17 (6H, m), 5,14 (2H, s), 5,95 (1H, s), 6,85-to 6.88 (1H, m), 7,09-7,17 (4H, m), 7,19-to 7.32 (7H, m).

Reference example 161

Synthesis of 1-[2-(1-biphenyl-4-reparacin-4-yl)ethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

The palladium acetate (34 mg, 0.15 mmol), tri-tert-butyltetrahydrofuran (66 mg, 0.23 mmol) and tert-piperonyl sodium (218 mg, of 2.27 mmol) was added to a toluene solution (10 ml) of 5-(1,3-dioxolane-2-yl)-1-(2-piperidine-4-retil)-3,4-dihydro-1H-quinoline-2-she (500 mg, of 1.52 mmol) and 4-bromobiphenyl (424 mg, 1.82 mmol), followed by stirring in an argon atmosphere at 100°C for 7.5 hours. After cooling to room temperature, to the reaction mixture were added water and ekstragirovaniem. The extract was dried over sodium sulfate and concentrated under reduced pressure and the residue was purified by chromatography on a column with a basic silica gel (n-hexane:ethyl acetate=2:1). The purified product was concentrated under reduced pressure and the residue was dissolved in acetone (10 ml). Added monohydrate p-toluensulfonate acid (104 mg) and water (2 ml), followed by boiling under reflux for 15 minutes. The resulting mixture was cooled to room temperature and concentrated under reduced pressure. The residue was made basic by addition of an aqueous potassium carbonate solution and washed for 10 minutes in the apparatus for ultrasonic cleaning. The obtained insoluble substance was separated by filtration, washed with water and dried to obtain 213 mg (yield: 32,1%) 1-[2-(1-biphenyl-4-reparacin-4-yl)ethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a colorless solid.

1H-NMR (CDCl3) δ ppm: 1,2-2,3 (7H, m), 2,6-2,7 (2H, m), from 3.0 to 3.25 (2H, m), 3,4-3,55 (2H, m), 3,65-3,8 (2H, m), 3.95 to a 4.1 (2H, m), 7,18 (1H, d, J=8.0 Hz), 7,25 to 7.7 (10H, m), to 7.84 (1H, d, J=8.1 Hz), 10,22 (1H, s).

Reference example 162

Synthesis of 1-[3-(4-chlorophenylsulfonyl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

1-(3-Bromopropyl)-5-(1,3-dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (797 mg, 2.34 mmol), 4-chlorothiophenol (407 mg, of 2.81 mmol) and potassium carbonate (421 mg, of 3.05 mmol) was added to acetonitrile (ml), followed by boiling under reflux for 5 hours. After cooling to room temperature, to the reaction mixture was added water and was extracted with ethyl acetate. The extract was dried over sodium sulfate and concentrated under reduced pressure and the residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=3:1→2:1). The purified product was concentrated under reduced pressure and the residue was dissolved in acetone (16 ml). Added monohydrate p-toluensulfonate acid (53,5 mg) and water (3 ml) followed by stirring at room temperature over night. Was added to the reaction mixture an aqueous solution of potassium carbonate and was extracted with dichloromethane. The organic layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 700 mg (yield: 83%) of 1-[3-(4-chlorophenylsulfonyl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a colorless oil.

1H-NMR (CDCl3) δ ppm: 1,9-of 2.05 (2H, m), 2,55-to 2.65 (2H, m), 2,9-3,05 (4H, m), 4,0-4,2 (6H, m)5,94 (1H, s), of 6.96 (1H, d, J=7.9 Hz), a 7.2 to 7.35 (6H, m).

Reference example 163

Synthesis of 1-[3-(4-benzylpiperidine-1-yl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde

1-(3-Bromopropyl)-5-(1,3-dioxolane-2-yl)-3,4-dihydro-1H-quinoline-2-he (790 mg, 2.32 mmol), 4-benzylpiperidine (0,49 ml, and 2.79 mmol) and potassium carbonate (142 mg, of 1.03 mmol) was added to acetonitrile (15 ml), followed Ki is achenium under reflux for 1.5 hours. After cooling to room temperature the reaction mixture was filtered to remove insoluble substances. The solid is washed with acetonitrile and the filtrate and wash water were combined and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=3:1→ethyl acetate:methanol=50:1). The purified product was concentrated under reduced pressure and the residue was dissolved in acetone (15 ml). Added monohydrate p-toluensulfonate acid (368 mg) and the resulting mixture was boiled under reflux for 2 hours. Was added to the reaction mixture an aqueous solution of potassium carbonate, followed by concentration under reduced pressure. To the residue was added water and was extracted with dichloromethane. The organic layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 672 mg (yield: quantitative) of 1-[3-(4-benzylpiperidine-1-yl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde in the form of a colorless oil.

1H-NMR (CDCl3) δ ppm: 1.2 to 1,95 (9H, m)to 2.35 (2H, t, J=7.0 Hz), 2,4-2,7 (4H, m), 2,8-3,1 (4H, m), 3,9-4,2 (6H, m)5,94 (1H, s), and 7.1 to 7.4 (8H, m).

Using the appropriate source materials and following the method of reference example 24 was synthesized compounds of reference examples 178 and 185, shown below./p>

Using the appropriate source materials and following the method of reference example 25 was synthesized compounds of reference examples 164, 165, 167-172, 176, 177, 179, 183 and 184, as shown below.

Using the appropriate source materials and following the method of reference example 26 was synthesized compounds of reference examples 186 to 190, 192, 193, 197, 198, 203 and 206-209, shown below.

Using the appropriate source materials and following the method of reference example 27 was synthesized compounds of reference examples 166 and 180-182 shown below.

Using the appropriate source materials and following the method of reference example 30 was synthesized compounds of reference examples 73, 196, 200, 201 and 210, shown below.

Using the appropriate source materials and following the method of reference example 158, synthesized the compound of reference example 175, shown below.

Using the appropriate source materials and following the method of reference example 159, synthesized the compounds of reference examples 173 and 174, as shown below.

Using the appropriate source materials and following the method of reference example 161 was synthesized compounds of reference examples 202, 204, 205 and 214, as shown below.

Using the appropriate source materials and following the method of reference example 162 was synthesized compounds of reference examples 191 and 195, pok is related below.

Using the appropriate source materials and following the method of reference example 163 was synthesized compounds of reference examples 194, 199 and 211-213 shown below.

Using the appropriate source materials and following the method of reference example 32, synthesized the compound of reference example 132, shown below.

Using the appropriate source materials and following the method of reference example 41 was synthesized compound of reference example 143, shown below.

Using the appropriate source materials and following the method of reference example 22, synthesized the compound of reference example 157, shown below.

Table 23-34 (see the end of the description).

Example 1

Synthesis of 5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)thiazolidine-2,4-dione

1.0 g of 2-chloro-3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propionic acid, 0.45 g of thiourea and 0.4 g of sodium acetate was added to 20 ml of methoxyethanol and the mixture was stirred at 110°C for 7.5 hours. The reaction mixture was concentrated under reduced pressure, to the residue was added an aqueous solution of sodium bicarbonate to precipitate solids and precipitated precipitated solid substance was separated by filtration. The filtrate was extracted with dichloromethane, the extract was dried over anhydrous sodium sulfate and concentrated. Concentrated OST the current and solid, collected by filtration, were combined and added to a mixed solvent of 10% hydrochloric acid and ethanol followed by heating and boiling under reflux overnight. Drove the solvent under reduced pressure and the residue was recrystallized from aqueous DMF to obtain 0,41 g of 5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)thiazolidine-2,4-dione as a yellow powder.

Melting point: 254°C to 255°C

Example 2

Synthesis of 5-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl]thiazolidine-2,4-dione

912 mg of 2-chloro-4-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)butyric acid, 390 mg of thiourea and 394 mg of sodium acetate was added to 20 ml of methoxyethanol, followed by stirring at 110°C for 4 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added water and the mixture was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated. The residue was added to a mixed solvent of 10 ml of 10% hydrochloric acid and 10 ml of ethanol followed by heating and boiling under reflux overnight. Drove the solvent under reduced pressure and the residue was recrystallized from a mixed solvent of DMF-ethanol to obtain 332 mg (31% yield) of 5-[2-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ileti]thiazolidin-2,4-dione as a yellow powder.

Melting point: 222°C 224°C

Example 3

Synthesis of 5-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]thiazolidin-2,4-dione

1 g of 2-chloro-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)valerianic acid, 380 mg of thiourea and 380 mg of sodium acetate was added to 20 ml of methoxyethanol, followed by stirring at 110°C for 5 hours. The reaction mixture was concentrated under reduced pressure and to the residue was added water and a small amount of ethanol to precipitate solids. Precipitated precipitated solid substance was separated by filtration. The solid is collected by filtration, was added to a mixed solvent of 10 ml of 10% hydrochloric acid and 10 ml of ethanol followed by heating and boiling under reflux overnight. Drove the solvent under reduced pressure and the residue was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated. The concentrated residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=100:1→10:1) and recrystallized from a mixed solvent of ethanol-ether to obtain 332 mg (29% yield) of 5-[3-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)propyl]thiazolidin-2,4-dione as a pale yellow powder.

Melting point: 172°C-175°C

Example 4

Synthesis of 5-(8-methoxy-1-methyl-2-oxo-1,2-d is hydrochinon-5-yl)thiazolidin-2,4-dione

to 3.02 g of chloro-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)ethyl acetate, 1.4 g of thiourea and 2 g of sodium acetate were added to 50 ml of methoxyethanol, followed by stirring at 110°C for 2.5 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added water to precipitate solids and precipitated precipitated solid substance was separated by filtration. The cooled solid was added to a mixed solvent of 30 ml of 10% hydrochloric acid and 30 ml of ethanol followed by heating and boiling under reflux overnight. The resulting mixture was concentrated under reduced pressure to half of its original volume. Added water and the mixture was cooled with ice to precipitate solids. Precipitated precipitated solid substance was separated by filtration. The solid is recrystallized from a mixed solvent of DMF-ethanol to obtain 1.68 g (57% yield) 5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)thiazolidin-2,4-dione in the form of a grey powder.

Melting point: 255°C (decomposition)

Example 5

Synthesis of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-iletiler]thiazolidin-2,4-dione

1.50 g of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-carboxaldehyde and 0,826 g of 2,4-thiazolidinedione suspended in 30 ml of toluene. Added five drops piperidin the a and five drops of acetic acid followed by heating and boiling under reflux for 6 hours. The resulting mixture was allowed to cool to precipitate solids and precipitated precipitated solid substance was separated by filtration and dried to obtain 1.01 g (50% yield) of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-iletiler]thiazolidin-2,4-dione as a light brown powder.

1H-NMR (DMSO-d6) δ ppm: of 5.53 (2H, s)6,76 (1H, s), 7,11-7,49 (6H, m), 7,53-to 7.64 (1H, m), 7,81 (1H, d, J=8.1 Hz), of 8.04 (1H, s), 12,21-13,32 (1H, usher.).

Example 6

Synthesis of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-iletiler]thiazolidin-2,4-dione

1.50 g of 1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxaldehyde and 0,826 g of 2,4-thiazolidinedione suspended in 30 ml of toluene and added five drops of piperidine and five drops of acetic acid followed by heating and boiling under reflux for 6 hours. The resulting mixture was allowed to cool to precipitate solids. Precipitated precipitated solid substance was separated by filtration and dried to obtain 1,36 g of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-iletiler]thiazolidin-2,4-dione as a yellow powder (68% yield).

1H-NMR (DMSO-d6) δ ppm: of 5.55 (2H, s), 7,18 was 7.45 (6H, m), 7,53-the 7.65 (1H, m), 7,88-of 8.00 (2H, m), 8,21 (1H, s), 12,59 (1H, users).

Using the appropriate source materials, used a technique similar to example 6, to obtain the compounds of the following examples 7-13.

Example 7

5-[1-(1-Biphenyl-4-and the methyl-2-oxo-1,2-dihydroquinoline-4-yl)methylidene]thiazolidin-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 5,59 (2H, users), is 6.78 (1H, s), 7.18 in-7,70 (12H, m), 7,82 (1H, d, J=8.0 Hz), with 8.05 (1H, s), 12,81 (1H, users).

Example 8

5-[1-(1-Biphenyl-4-ylmethyl-2-oxo-1,2-dihydroquinoline-3-yl)methylidene]thiazolidin-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 5,61 (2H, users), 7,21-7,51 (7H, m), 7,51-to 7.68 (5H, m), 7,87-of 8.00 (2H, m), by 8.22 (1H, s), 12,60 (1H, users).

Example 9

5-[1-(8-Methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)methylidene]thiazolidin-2,4-dione

Melting point: 300°C or higher

1H-NMR (DMSO-d6) δ ppm: of 3.80 (3H, s), of 3.95 (3H, s)6,70 (1H, d, J=9.8 Hz), 7,35-7,45 (2H, m), with 8.05 (1H, d, J=9.8 Hz), 8,14 (1H, s), 12,63 (1H, users).

Example 10

5-[1-(8-Methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-yl)methylidene]-3-methylthiazolidine-2,4-dione

Melting point: 270°C (decomposition)

Example 11

5-{1-[8-Methoxy-1-(4-bromobenzyl)-2-oxo-1,2-dihydroquinoline-5-yl]methylidene}thiazolidin-2,4-dione

1H-NMR (DMSO-d6) δ ppm: the 3.65 (3H, s), 5,67 (2H, s), to 6.80 (1H, d, J=9.8 Hz), 7,03 (2H, d, J=8.5 Hz), 7,25-7,40 (2H, m), 7,40-7,52 (2H, m), 8,16 (2H, d, J=10,9 Hz), 12,64 (1H, users).

Example 12

5-[1-(1-Biphenyl-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)methylidene]thiazolidin-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 2,70-2,84 (2H, m), 2,97-to 3.09 (2H, m), with 5.22 (2H, users), 7,12 (1H, s), 7,15-of 7.25 (1H, m), 7,25-7,49 (6H, m), 7,56-7,71 (5H, m), to 12.52 (1H, users).

Example 13

5-[1-(1-Biphenyl-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-8-yl)methylidene]thiazolidin-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 2,55 of 2.68(2H, m), 2,80-to 2.94 (2H, m), to 4.98 (2H, s), 6,98-7,16 (3H, m), 7,22-7,63 (9H, m), of 7.75 (1H, s), 12,57 (1H, users).

Example 14

Synthesis of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-ylmethyl]thiazolidine-2,4-dione

0.96 g of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-iletiler]thiazolidin-2,4-dione, 0,735 g diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and 0.96 g of silica gel was added to 30 ml of toluene, followed by heating and boiling under reflux overnight. Drove the solvent and the residue was purified by chromatography on a column of silica gel (dichloromethane:ethyl acetate=10:1→3:1) and the purified product was recrystallized from a mixed solvent of chloroform-ether to obtain 0.87 g (91% yield) of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 142,1°C-143,7°C

Example 15

Synthesis of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-ylmethyl]thiazolidine-2,4-dione

1,207 g of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-3-iletiler]thiazolidin-2,4-dione, 0,924 g of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and 1.2 g of silica gel was added to 30 ml of toluene, followed by heating and boiling under reflux overnight. Was added to the reaction solution even of 0.77 g of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate followed by heating and boiling under reflux within the eyes. Drove the solvent and the residue was purified by chromatography on a column of silica gel (dichloromethane:ethyl acetate=10:1→3:1). The purified product was recrystallized from a mixed solvent of chloroform-ether to obtain 0.74 g (61% yield) of 5-[1-(4-Chlorobenzyl)-2-oxo-1,2-dihydroquinoline-4-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 230,7°C-231,9°C

Using the appropriate source materials, used a technique similar to example 15, to obtain the compounds of the following examples 16-19.

Example 16

5-(2-Oxo-1,2-dihydroquinoline-3-ylmethyl)thiazolidine-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 2,45-to 2.55 (1H, m), 3,35-3,5 (1H, m), 4,9-5,0 (1H, m), 7,15-in 7.7 (4H, m), to 7.84 (1H, s), 11,91 (1H, users), 12,08 (1H, users).

Example 17

5-[1-(Biphenyl-4-ylmethyl)-2-oxo-1,2-dihydroquinoline-3-ylmethyl]thiazolidine-2,4-dione

Melting point: 220,4°C-221,8°C

Example 18

5-[1-(Biphenyl-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-ylmethyl]thiazolidine-2,4-dione

Melting point: 213,2°C-213,7°C

Example 19

5-[1-(Biphenyl-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-8-ylmethyl]thiazolidine-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 2,40 of $ 2.53 (2H, m), 2,70-to 2.85 (2H, m), 3,09 is 3.25 (1H, m), 3,50-of 3.64 (1H, m), 4,79-of 4.90 (1H, m), 4,90-5,16 (2H, m), 7,02 (1H, t, J=7.5 Hz), 7,08-7,21 (4H, m), 7,28-to 7.64 (7H, m), 12,04 (1H, s).

Example 20

Synthesis of 5-[8-methoxy-1-(4-nitrobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

600 mg of 5-[methoxy-1-(4-nitrobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler]thiazolidin-2,4-dione, 415 mg of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and 600 mg of silica gel was added to 20 ml of toluene followed by heating and boiling under reflux for 14 hours. Drove the solvent and the residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=4:1→1:1). The purified product was recrystallized from a mixed solvent of ethyl acetate-ether to obtain 585 mg (97% yield) of 5-[8-methoxy-1-(4-nitrobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 246,5°C-246,6°C.

Example 21

Synthesis of 5-[1-(4-aminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

10 g of 10% palladium on carbon was added to a DMF solution (100 ml) 10.0 g of 5-[8-methoxy-1-(4-nitrobenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione and the mixture was subjected to catalytic recovery at 40°C for 5 hours. The catalyst was removed by filtration and the filtrate was concentrated. To the residue was added ethyl acetate and water and was carried out by filtration through celite. The filtrate was washed with water and dried over anhydrous magnesium sulfate, followed by concentration. The residue was purified by chromatography on silica gel (n-hexane:ethyl acetate=4:1→1:4) and the purified product was recrystallized with ethyl acetate receiving 7.98 g (86% yield) of 5-[1-(4-aminobenzyl)-8-is ethoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 174,1°C-174,8°C

Example 22

Synthesis of 5-{8-methoxy-1-[4-(2-naphthylamine)benzyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

0.52 g of triethylamine and 0.42 g of diethylphosphoramidite (DEPC) was added under ice cooling to a DMF solution (14 ml) 0.7 g of 5-[1-(4-aminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione and 0.59 g of 2-naphthoic acid, followed by stirring for 16 hours. Was added to the reaction solution, water and ethyl acetate and the resulting insoluble matter was separated by filtration. Assembled insoluble substance was dissolved in a mixed solvent of dichloromethane-methanol and concentrated. The residue was washed with diethyl ether and diisopropyl ether. The residue was dried under reduced pressure to obtain 0.74 g (77% yield) of 5-{8-methoxy-1-[4-(2-naphthylamine)benzyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione as a white amorphous solid.

Melting point: 202°C to 208°C

1H-NMR (DMSO-d6) δ ppm: 2,44-2,52 (2H, m), 2,82-is 2.88 (2H, m), 3,03-3,13 (1H, m), 3,35 is-3.45 (1H, m), of 3.73 (3H, s), 4,79 (1H, DD, J1=4,1 Hz, J2=9.9 Hz), 5,20 (2H, s), 6,83 (1H, d, J=8.6 Hz), 6,91 (1H, d, J=8.6 Hz), 7,05 (2H, d, J=8,4 Hz), 7,58-7,66 (4H, m), 7,95-8,08 (4H, m), charged 8.52 (1H, s), 10,33 (1H, s), 12,06 (1H, s).

Example 23

Synthesis of 5-[1-(4-ventilatsioonikambri)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]TIA who alidin-2,4-dione

0.6 g of 5-[1-(4-aminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione suspended in dichloromethane (6 ml) was added 4 ml of pyridine under ice cooling to form a solution. To the resulting solution was added 0.26 g of ameliorate, followed by stirring for 1 hour. Was added to the reaction solution 1N. hydrochloric acid and the mixture was extracted with ethyl acetate. The extract was washed twice with water and once with saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=2:1→1:1) and recrystallized from diisopropyl ether to obtain 3.75 g (97% yield) of 5-[1-(4-ventilatsioonikambri)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 98°C-102°C.

Example 24

Synthesis of 5-[8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler]thiazolidin-2,4-dione

7.0 g of 8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde and 3.25 g of 2,4-thiazolidinedione suspended in 70 ml of toluene. Added ten drops of piperidine and ten drops of acetic acid followed by heating and boiling under reflux in the course is e 4 hours. The resulting mixture was allowed to cool to precipitate solids and precipitated precipitated solid substance was separated by filtration and dried to obtain 8.0 g (90% yield) of 5-[8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler]thiazolidin-2,4-dione as a pale yellow powder.

1H-NMR (DMSO-d6) δ ppm: 2,52-of 2.66 (2H, m), 2.91 in was 3.05 (2H, m), the 3.65 (3H, s), with 3.79 (3H, s)to 5.17 (2H, s), 7,02 (1H, d, J=8.7 Hz), 7,16 (1H, d, J=8.7 Hz), 7,25 (2H, d, J=8,3 Hz), 7,74-of 7.90 (3H, m), 12,55 (1H, users).

Example 25

Synthesis of 5-[8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

7.0 g of 10% palladium on carbon was added to a DMF solution (70 ml) 7.0 g of 5-[8-methoxy-1-(4-methoxycarbonyl benzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler]thiazolidin-2,4-dione was carried out by catalytic reduction at 40°C for 5 hours. The catalyst was removed by filtration and the filtrate was concentrated. The residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=4:1→1:1). The purified product was recrystallized from a mixed solvent of ethyl acetate-diethyl ether to obtain 5,23 g (74% yield) of 5-[8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione as a white powder.

Melting point: 193,1°C-195,5°C

Example 26

Synthesis of 5-[8-methoxy-1-(4-carboxybenzoyl)-2-oxo-1,2,34-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

35 ml of 1N. an aqueous solution of lithium hydroxide was added to a mixed solution of ethanol (200 ml) and THF (200 ml) 4.0 g of 5-[8-methoxy-1-(4-methoxycarbonylbenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione, followed by stirring at room temperature over night. Drove the solvent under reduced pressure, to the residue was added dilute hydrochloric acid and the resulting insoluble matter was separated by filtration. Assembled insoluble substance was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=1:1→1:3) and recrystallized from ethyl acetate to obtain 3.75 g (97% yield) of 5-[8-methoxy-1-(4-carboxybenzoyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione as a white powder.

1H-NMR (DMSO-d6) δ ppm: 2,42-2,61 (2H, m), 2,70-to 2.94 (2H, m), 3,01 is 3.15 (1H, m), 3,34-of 3.48 (1H, m), of 3.56 (3H, s), 4,78 (1H, DD, J=4,4, 9.8 Hz), to 5.17 (2H, users), for 6.81 (1H, d, J=8.6 Hz), 6.90 to (1H, d, J=8.6 Hz), 7,17 (2H, d, J=8,2 Hz), to 7.77 (2H, d, J=8,2 Hz), 12,06 (1H, users), of 12.76 (1H, users).

Example 27

Synthesis of 5-{1-[4-(4-isopropylaminocarbonyl)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

0.34 g of triethylamine and 0.28 g of diethylphosphoramidite (DEPC) was added under ice cooling to a DMF solution (10 ml), 0.5 g of 5-[8-methoxy-1-(4-carboxybenzoyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione and 0.23 g of 4-isopropylaniline with p the following stirring for 0.5 hours. Was added to the reaction solution, water, and the mixture was extracted with ethyl acetate. The organic layer was washed twice with water and once with saturated sodium chloride solution and dried over anhydrous sodium sulfate. Drove the solvent under reduced pressure, the residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=100:1→20:1) and recrystallized from a mixed solvent of ethyl acetate and n-hexane to obtain 0,57 g (64% yield) of 5-{1-[4-(4-isopropylaminocarbonyl)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione as a white powder.

Melting point: 243°C-244°C.

Using the appropriate source materials, used a technique similar to example 27, to obtain the compounds of the following examples 28 and 29.

Example 28

5-{8-Methoxy-1-[4-(piperidine-1-carbonyl)benzyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

1H-NMR (DMSO-d6) δ ppm: to 1.25 and 1.80 (6H, m), 2,39-2,62 (2H, m), 2,72-2,95 (2H, m), 2.95 and-3,72 (9H, m), of 4.77 (1H, DD, J=4,3, 9.6 Hz), 5,16 (2H, s), for 6.81 (1H, d, J=8.6 Hz), 6.90 to (1H, d, J=8.6 Hz), to 7.09 (2H, d, J=8.0 Hz), 7,18 (2H,, d, J=8.0 Hz), a 12.05 (1H, users).

Example 29

5-[1-(4-Cyclohexanecarbonitrile)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

1H-NMR (DMSO-d6) δ ppm: 0,95-of 1.85 (10H, m), 2,39-2,60 (2H, m), 2,70-to 2.94 (2H, m), 3.00 and-3,19 (1H, m), 3,23-3,50 (1H, m), 3,63 (3H, s), 3,80-to 3.99 (1H, m), with 4.64-4,88 (1H, m), 5,19 (2H,s), to 6.80 (1H, d, J=8.6 Hz), 6.89 in (1H, d, J=8.6 Hz), 7,11 (2H, d, J=8.0 Hz), the 7.65 (2H, d, J=8.0 Hz), 8,03 (1H, d, J=7.8 Hz), 12,06 (1H, users).

Example 30

Synthesis of 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler)thiazolidin-2,4-dione

2.0 g of 1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde and 0,874 g of 2,4-thiazolidinedione suspended in 20 ml of toluene. Added ten drops of piperidine and ten drops of acetic acid followed by heating and boiling under reflux for 8 hours. The resulting mixture was allowed to cool to precipitate solids which precipitated precipitated solid substance was separated by filtration and dried to obtain 2.7 g (92% yield) 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler)thiazolidin-2,4-dione as a yellow powder.

1H-NMR (DMSO-d6) δ ppm: 2,41-2,60 (2H, m), 2,75 are 2.98 (2H, m), 5,31 (2H, s), at 6.84 (1H, d, J=8.6 Hz), 7,00-7,30 (6H, m), 7,81 (1H, s), of 10.72 (1H, s), 12,48 (1H, users).

Example 31

Synthesis of 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

2.2 g of 10% palladium on carbon was added to a DMF solution (20 ml) 2.2 g of 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-iletiler)thiazolidin-2,4-dione and the mixture was subjected to catalytic recovery at room temperature for 2 hours. The catalyst was removed by filtration and the filtrate was concentrated. The residue dissolve the Yali in ethyl acetate, washed with water and saturated sodium chloride solution and concentrated. The residue was purified by chromatography on a column of silica gel (dichloromethane:methanol=50:1). The purified product was recrystallized from a mixed solvent of dichloromethane-ether to obtain 1.9 g (88% yield) 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione as a white powder.

Melting point: 213,2°C-213,7°C

Example 32

Synthesis of 5-(1-benzyl-8-butoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

of 55.5 mg of tert-piperonyl potassium was added to a DMSO solution (1 ml) 90 mg of 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione, followed by stirring at room temperature for 1 hour. To the mixture was added to 29.8 μl of 4-iodobutane, followed by stirring at room temperature for 2 hours. Was added to the reaction solution, water, to the mixture was added potassium hydrosulfate and the resulting mixture was extracted with ethyl acetate. After washing with water, the extract was dried over anhydrous magnesium sulfate and concentrated. The residue was purified preparative thin-layer chromatography on silica gel (dichloromethane:methanol=20:1) to give 42 mg (41% yield) 5-(1-benzyl-8-butoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione as a colorless amorphous solid.

1H-NMR (CDCl3) δ ppm: of 0.93 (3H, t, J=7,3 Hz), 1,35 of 1.50 (2H, m), 1,57-of 1.73 (2H, m), 2,52-to 2.67 (2H, m), 2,67-2,95 (2H, m), 3,05 (1H, DD, J=10.1 Hz, J=14,0 Hz), 3,51 (1H, DD, J=4.0 Hz, J=14,0 Hz)to 3.89 (2H, t, J=6.6 Hz), 4,39 (1H, DD, J=4.0 Hz, J=10.1 Hz), 5,32 (2H, s)of 6.71 (1H, d, J=8.6 Hz), 6.87 in (1H, d, J=8.6 Hz), 7,02-of 7.25 (5H, m)to 9.15 (1H, users).

Example 33

Synthesis of 5-(1-benzyl-8-benzyloxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

of 55.5 mg of tert-piperonyl potassium was added to a DMSO solution (1 ml) 90 mg of 5-(1-benzyl-8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione, followed by stirring at room temperature for 1 hour. Added 30 μl of benzylbromide, followed by stirring at room temperature for 1 hour. Was added to the reaction solution, water, to the mixture was added potassium hydrosulfate and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified preparative thin-layer chromatography on silica gel (dichloromethane:methanol=20:1) obtaining of 84.5 mg (76% yield) 5-(1-benzyl-8-benzyloxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione as a colorless amorphous solid.

1H-NMR (CDCl3) δ ppm: 2,49-to 2.65 (2H, m), 2,65-to 2.94 (2H, m), of 3.07 (1H, DD, J=10.0 Hz, J=14,5 Hz), 3,51 (1H, DD, J=4,1 Hz, J=14,5 Hz), 4,39 (1H, DD, J=4,1 Hz, J=10.0 Hz), equal to 4.97 (2H, s), 5,32 (2H, s)6,76 (1H, d, J=8.6 Hz), 6,86 (1H, d, J=8.6 Hz), 6,93-7,02 (2H, m), 7.03 is-7,19 (3H, m), 7,29-745 (5H, m), 9,07 (1H, users).

Example 34

Synthesis of 5-(1-carboxymethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

of 4.16 g of 1-tert-butoxycarbonylmethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde and 1.66 g of 2,4-thiazolidinedione (1.00 equiv.) suspended in 40 ml of toluene and added two drops of acetic acid and two drops of piperidine followed by heating and boiling under reflux for 13 hours using traps Dean-stark. After cooling, the crystals were separated by filtration and washed with toluene. The obtained crystals suspended in a 3.15 g of silica gel, 2,09 g of dihydropyridines and 60 ml of toluene, followed by heating and boiling under reflux overnight. Added 3,15 g of silica gel, drove away the solvent under reduced pressure, the residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=2:1) and recrystallized from a mixture of ethyl acetate-hexane to obtain 2,13 g (38% yield) 5-(1-carboxymethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione as a white powder.

Melting point: 251°C to 255°C

Example 35

Synthesis of potassium salt of 5-{1-[N-(3-triptoreline)amino]carbonylmethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

500 mg of 5-(1-carboxymethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-metil)thiazolidin-2,4-dione was dissolved in 5 ml of DMF. To the solution was added 0.35 ml 3-triptorelin, 0.32 g of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC) and 0.25 g of 1-hydroxybenzotriazole (HOBT) followed by stirring at room temperature over night. Was added to the reaction solution, water, and the obtained solid substance was separated by filtration. The solid was dissolved in methylene chloride, washed with sodium chloride solution and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (methylene chloride:methanol=50:1) to give 412 mg of 5-{1-[N-(3-triptoreline)amino]carbonylmethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione.

Obtained 5-{1-[N-(3-trifluoromethyl phenyl)amino]carbonylmethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione was dissolved in 4 ml of THF. Added 84,5 mg of tert-butoxide potassium to dissolve the solids. Added diethyl ether and triturated. The obtained crystals were separated by filtration and dried to obtain 340 mg (49% yield) of the potassium salt of 5-{1-[N-(3-triptoreline)amino]carbonylmethyl-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione as a brown powder.

Melting point: 135°C-139,5°C.

Example 36

Synthesis of 5-(8-methoxy-1-piperidine-4-ylmethyl-2-the CSR-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

1.7 g of 5-[8-methoxy-1-(1-tert-butoxycarbonylamino-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione was added to 50 ml of 4n. an ethyl acetate solution of hydrogen chloride, followed by stirring at room temperature for 6 hours. The resulting mixture was concentrated under reduced pressure and to the residue was added an aqueous solution of sodium bicarbonate. The resulting insoluble matter was separated by filtration and dried to obtain 1.5 g (yield: quantitative) 5-(8-methoxy-1-piperidine-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione as a white powder.

1H-NMR (DMSO-d6) δ ppm: 1,05-1,3 (2H, m), 1,4-1,7 (3H, m), 2,3-2,9 (6H, m), from 3.0 to 3.25 (3H, m), 3,82 (3H, s), 4.00 points (2H, d, J=6.8 Hz), 4,63 (1H, DD, J=8.7 Hz, J=4, 2 Hz), 6,9-7,05 (2H, m).

Example 37

Synthesis of 5-(1-{2-[1-(4-methylbenzoyl)piperidine-4-yl]ethyl}-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione

2 ml of DMF was added to 100 mg of 5-{1-[2-(1-piperidine-4-yl)ethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione, 42.2 mg p-Truelove acid, to 59.4 mg of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC) and 43.5 mg of 1-hydroxybenzotriazole (HOBt) followed by stirring at room temperature for 2.5 hours. Added water, the mixture was stirred for some time and the obtained solid substance was separated by filtering what W. The cooled solid was dissolved in methylene chloride and purified by chromatography on silica gel (methylene chloride:methanol=20:1) to obtain the 68,4 mg (97% yield) of the target compound as a white solid.

Melting point: 60°C-65°C.

Example 38

Synthesis of 5-[1-(5-benzyl-6-oxo-5,6-dihydropteridine-2-yl)methylidene]thiazolidin-2,4-dione

592 mg of 5-benzyl-6-oxo-5,6-dihydropteridine-2-carboxaldehyde and 221 mg of 2,4-thiazolidinedione suspended in 10 ml of toluene. To the suspension was added two drops of acetic acid and two drops of piperidine followed by heating and boiling under reflux overnight. The reaction solution was cooled and the resulting solid substance was separated by filtration. The cooled solid was washed with a mixture of toluene : diethyl ether and dried to obtain 620 mg (80% yield) of 5-[1-(5-benzyl-6-oxo-5,6-dihydropteridine-2-yl)methylidene]thiazolidin-2,4-dione as a yellow solid.

1H-NMR (DMSO-d6) δ ppm: 5,67 (2H, s), 7,0-8,0 (10H, m), to 8.45 (1H, DD, J=8.0 Hz, 1.3 Hz), at 8.60 (1H, d, J=8.0 Hz), 8,80 (1H, d, J=1,8 Hz), and 12.6 (1H, users).

Example 39

Synthesis of 5-[1-(5-benzyl-6-oxo-5,6-dihydropteridine-2-yl)methyl]thiazolidin-2,4-dione

620 mg of 5-[1-(5-benzyl-6-oxo-5,6-dihydropteridine-2-yl)methylidene]thiazolidin-2,4-dione was dissolved 2.31 ml of THF. To the solution was added 2,31 ml of pyridine and 2,31 ml THF solution of 2M borohydride lit is I followed by heating and boiling under reflux for 4 hours. The reaction solution was cooled, acidified with diluted hydrochloric acid and was extracted with dichloromethane. The organic layer was washed with water, then saturated sodium chloride solution and dried over sodium sulfate. After filtration drove away the solvent under reduced pressure, the residue was led using dichloromethane and the resulting solid substance was separated by filtration. The solid is separated by filtration, subjected to air drying to obtain 232 mg (36% yield) of 5-[1-(5-benzyl-6-oxo-5,6-dihydropteridine-2-yl)methyl]thiazolidin-2,4-dione as white crystals.

1H-NMR (DMSO-d6) δ ppm: 3,1-3,7 (2H, m), 5,04 (1H, DD, J=a 13.8 Hz, J=4,8 Hz), USD 5.76 (2H, s), 7,1 was 7.45 (5H, m), about 7.6 to 8.0 (2H, m), of 8.3 and 8.6 (3H, m), 12,0 (1H, users).

Example 40

Synthesis of 5-{8-methoxy-1-[1-(2-methylbenzyl)piperidine-4-yl]methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

To 5-(8-methoxy-1-piperidine-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione (20 µmol, 1.0 EQ.) added a DMF solution (200 ál) 2-methylbenzaldehyde (24 mmol, 1.2 equiv.) and acetic acid (10 μl). We also added a mixture of Si-cyanoborohydride sodium. The solution was shaken for a few minutes, was added diisopropylethylamine (30 μl) and the reaction was performed at room temperature over night. The resin was removed by filtration and washed with dichloromethane. From what illitrate drove the solvent in a stream of gaseous nitrogen and the residue was purified HPLC (UV-trigger, column: CAPCELL CANCER C18, UG 120 S-5, 20 mmh mm, 0,05% triperoxonane acid-N2Oh, 0,05% triperoxonane acid-CH3JV). Confirmed the structure of LC-MS and was dried by freezing to obtain 5-{8-methoxy-1-[1-(2-methylbenzyl)piperidine-4-yl]methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione with the release of 50.5%.

MS: 508 (M+1)

Example 41

Synthesis of 5-{8-methoxy-1-[1-(tetrahydropyran-4-yl)piperidine-4-yl]methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

To 5-(8-methoxy-1-piperidine-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl)thiazolidine-2,4-dione (20 µmol, 1.0 EQ.) added a DMF solution (200 μl) tetrahydropyran-4-it (24 mmol, 1.2 equiv.) and acetic acid (10 μl). We also added a mixture of Mr triacetoxyborohydride sodium. Then the solution was shaken for several minutes, was added DIEA (30 μl) and the reaction was performed at 60°C over night. The resin was removed by filtration and washed with methylene chloride. Drove the solvent using nitrogen gas and the residue was purified HPLC (UV trigger, column: CAPCELL PAK C18, UG 120 S-5, 20 mm×50 mm, 0,05% triperoxonane acid-H2O, 0.05% of triperoxonane acid-CH3CN). Confirmed the structure of LC-MS and was dried by freezing to obtain 5-{8-methoxy-1-[1-(tetrahydropyran-4-yl)piperidine-4-yl]methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione with 30%yield.

+1)

Example 42

Synthesis of 5-[1-(4-methanesulfonylaminoethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione

To a dichloromethane solution (20 ml) and 1.00 g (0,00243 mm) 5-[1-(4-aminobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione was sequentially added pyridine (2.0 ml) and 0.21 ml (0,0027 mm) methanesulfonanilide under ice cooling with stirring. The mixture was stirred at the same temperature for 30 minutes and added water to terminate the reaction. The resulting mixture was washed twice with water and once with saturated sodium chloride solution), dried (magnesium sulfate) and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (dichloromethane:ethyl acetate=1:10→1:1) to obtain 1.1 g (92% yield) of the target compound as a white amorphous solid.

1H-NMR (DMSO-d6) δ ppm: 2,39-of 2.54 (2H, m), 2,72-2,87 (2H, m), is 2.88 (3H, s), 3,05 (1H, DD, J=10.0 Hz, J=14.4 Hz), 3,39 (1H, DD, J=4.0 Hz, J=14.4 Hz), to 3.67 (3H, s), was 4.76 (1H, DD, J=4.0 Hz, J=10.0 Hz), 5,13 (2H, s), to 6.80 (1H, d, J=8.6 Hz), 6.89 in (1H, d, J=8.6 Hz), 6,93-7,06 (4H, m), to 9.57 (1H, s), a 12.05 (1H, s).

Example 43

Synthesis of 3-methoxycarbonylmethyl-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)thiazolidine-2,4-dione

350 mg of 5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)thiazolidine-2,4-dione was dissolved in 5 ml of DMF. To the solution was added 0,156 ml methylpropan the Tata and 0.25 g of potassium carbonate, followed by stirring at room temperature over night. Added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated solution of sodium chloride and dried over sodium sulfate. After filtration drove away the solvent under reduced pressure. The residue was purified by chromatography on silica gel and recrystallized from methanol-acetone to obtain 245 mg (57% yield) of 3-methoxycarbonylmethyl-5-(8-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-5-ylmethyl)thiazolidine-2,4-dione as white crystals.

Melting point: 182°C 184°C

Example 44

Synthesis of 1-(biphenyl-4-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-3,4-dihydro-1H-quinoline-2-it

1.50 g of 1-(biphenyl-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde and 0,761 g 2 thioxo-1,3-thiazolidin-4-it is suspended in 20 ml of toluene. To the suspension was added two drops of piperidine and two drops of acetic acid followed by heating and boiling under reflux for 4 hours. Allowing the mixture to cool, precipitated precipitated solid substance was separated by filtration and dried to obtain 2,34 g (91% yield) of 1-(biphenyl-4-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of a yellow powder.

1H-NMR (DMSO-d6) δ ppm: was 2.76-of 2.81 (2H, m), 3.04 from-to 3.09 (2H, m), 5,23 (2H, m), 7,10-7,47 (8H, m), 7,54 (1H, s), to 7.59-the 7.65 (4H, m), 13,78 (1H, users).

Using the appropriate starting material, was used, and the illogical example 44, getting connection the following example 45.

Example 45

1-(4-Bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-3,4-dihydro-1H-quinoline-2-he

1H-NMR (DMSO-d6) δ ppm: 2,67 is 2.80 (2H, m), 2,93-to 3.09 (2H, m), 5,14 (2H, s),? 7.04 baby mortality (1H, d, J=8.6 Hz), 7,10-of 7.25 (2H, m), 7,32-EUR 7.57 (5H, m), 13,77 (1H, users).

Example 46

Synthesis of 1-(biphenyl-4-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

To 20 ml of toluene was added 1.4 g of 1-(biphenyl-4-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-3,4-dihydro-1H-quinoline-2-it, 1.01 g diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and 1.4 g of silica gel, followed by heating and boiling under reflux overnight. Drove the solvent and the residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=4:1→2:1). The purified product was recrystallized from toluene to obtain 0.84 g (60% yield) of 1-(biphenyl-4-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of white powder.

Melting point: 186,3°C-187,1°C

Example 47

Synthesis of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

50 mg of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-3,4-dihydro-1H-quinoline-2-it is suspended in a mixed solvent of 0.15 ml of methanol, 0.1 ml of water, and 0.08 ml of 1N. aqueous sodium hydroxide solution and 0.1 ml of THF. Then the suspension doba is Lyali 0,03 ml DMF solution (5 ml) 42 mg 6-hydrate of cobalt chloride and 250 mg dimethylglyoxime and the mixture was heated to 30°C-40°C. Was added an aqueous solution (0.1 ml) 15 mg of sodium borohydride, followed by stirring for 30 minutes. Was added a saturated aqueous solution of potassium hydrosulfate, the mixture was extracted with ethyl acetate and the extract was washed with water. The extract was dried over anhydrous magnesium sulfate and concentrated. The residue was purified preparative thin-layer chromatography on silica gel (ethyl acetate:n-hexane=1:1) obtaining of 44.7 mg (89% yield) of 1-(4-bromobenzyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of colorless amorphous solid, which is then recrystallized from a mixture of ethyl acetate-diethyl ether to obtain white powder.

Melting point: 191,3°C-USD 192.1°C

Using the appropriate starting material, was used a technique similar to example 47, to obtain the compound of the following example 48.

Example 48

Hydrochloride of 1-(6-chloropyridin-3-ylmethyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

Melting point: 70°C-80°C

Using the appropriate source materials, used a technique similar to example 6, to obtain the compounds of the following examples, 49-110.

Using the appropriate source materials, used a technique similar to example 15, to obtain the compounds of the following examples, 111-119, 121-131, 134-138, 140-144, 148, 150-153, 156-159, 161 to 165, 173, 177-182, 184-188, 859-860,965-969, 975-976 and 986-1001.

Using the appropriate source materials, used a technique similar to example 21, to obtain the compounds of the following examples, 120 and 133.

Using the appropriate source materials, used a technique similar to example 22, to obtain the compounds of the following examples, 189-225 and 258-291.

Using the appropriate source materials, used a technique similar to example 23, to obtain the compounds of the following examples, 228-257, 292-309, 656-658, 664, 666-667, 681-686 and 690-694.

Using the appropriate source materials, used a technique similar to example 27, to obtain the compounds of the following examples, 176, 310-545 and 1034.

Using the appropriate source materials, used a technique similar to example 32, to obtain the compounds of the following examples 546-606.

Using the appropriate source materials, used a technique similar to example 35, to obtain the compounds of the following examples, 607-613, 614-655, 659-663, 665, 668-680 and 687-689.

Using the appropriate source materials, used a technique similar to example 38, to obtain the compounds of the following examples, 695-699 and 921-959.

Using the appropriate source materials, used a technique similar to example 39, to obtain the compounds of the following examples, 139, 145-147, 154-155, 166-172, 174-175, 700-704, 913-920, 960-964, 970-972 and 977-985.

Using the appropriate source is e substances, used a technique similar to example 40, to obtain the compounds of the following examples 705-759.

Using the appropriate source materials, used a technique similar to example 42, to obtain the compounds of the following examples 760-855.

Using the appropriate source materials, used a technique similar to example 43, to obtain the compounds of the following examples, 857 and 861-912.

Using the appropriate source materials, used a technique similar to example 6, to obtain the compounds of examples 1002-1031.

Using the appropriate source materials, used a technique similar to example 15, to obtain the compounds of examples 1032-1033, 1038, 1041-1045, 1047, 1050-1055, 1057-1058, 1069-1070, 1076-1079 and 1088.

Using the appropriate source materials, used a technique similar to example 23, to obtain the compound of example 1059.

Using the appropriate source materials, used a technique similar to example 35, to obtain the compounds of examples 1115-1314.

Using the appropriate source materials, used a technique similar to example 36, to obtain the compounds of examples 160 and 1056.

Using the appropriate source materials, used a technique similar to example 47, to obtain the compounds of examples 974, 1035-1037, 1039-1040, 1048, 1060-1068, 1071-1075, 1080-1087 and 1089-1090.

Used a technique similar to example 1, with the teachings of the compounds of example 856.

Using the appropriate source materials, used a technique similar to example 1317, to obtain the compounds of examples 1049 and 1091-1114.

Using the appropriate source materials, used a technique similar to example 25, to obtain the compounds of the following examples, 226, 227 and 1046.

Using the appropriate source materials, used a technique similar to example 26, to obtain the compounds of the following examples, 149, 858 and 973.

Using the appropriate starting material, was used a technique similar to example 31, to obtain the compound of the following example 183.

Using the appropriate starting material, was used a technique similar to example 34, to obtain the compound of the following example 132.

Table 35-182 (see the end of the description).

Example 1315

Synthesis of 8-methoxy-1-(3-methylbutyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it

3.0 g of 8-methoxy-1-(3-methylbutyl)-4-ylmethyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-carboxaldehyde and 1.53 g of 2-thioxo-1,3-thiazolidin-4-it is suspended in 30 ml of toluene. Added five drops of piperidine and five drops of acetic acid followed by heating and boiling under reflux overnight. Allowing the mixture to cool, precipitated precipitated solid substance was separated by filtration and dried, then suspended in 16 ml of toluene. To the suspension was added to 2.2 g of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and 4.0 g of silica gel, followed by heating and boiling under reflux overnight. From the reaction mixture kept off the solvent and the residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=3:1→1:1). The purified product was recrystallized from a mixed solvent of ethyl acetate-n-hexane to obtain 2,11 g (55,2% yield) of 8-methoxy-1-(3-methylbutyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it is in the form of a yellow powder.

Melting point: 139,5°C 141°C

Example 1316

Synthesis of 5-[1-(3-hydroxypropyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]-3-titillation-2,4-dione

DMF solution (10 ml) 1.0 g (2,99 mmol) 5-[1-(3-hydroxypropyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione and 0,455 g (3,29 mmol) of potassium carbonate was cooled with ice and added 0,876 g (totaling 3.04 mmol) triphenylmethylchloride, followed by stirring at room temperature over night. Was added to the reaction solution, water, and the mixture was extracted with ethyl acetate. The organic layer was washed twice with water and once with saturated sodium chloride solution and concentrated under reduced pressure. The residue was purified by chromatography on a column of silica gel (n-hexane:ethyl acetate=2:1→ethyl acetate). The purified product was concentrated under reduced pressure and evaporated to dryness to obtain 700 mg (40,6% yield) of 5-[1-(3-hydroxypropyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]-3-titillation-2,4-dione in the form of bescoto the amorphous solids.

Example 1317

Synthesis of 5-{1-[3-(4-methylphenoxy)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione

THF solution (2 ml) 100 mg (0.18 mmol) of 5-[1-(3-hydroxypropyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]-3-titillation-2,4-dione, 0,0363 ml (0,347 mmol) of p-cresol and to 91.1 mg (0.35 mmol) of triphenylphosphine was cooled with ice. Was added to the solution in an argon atmosphere 0,158 ml diethyl ester of azodicarboxylic acid (2,2M toluene solution). The mixture was stirred at room temperature for two hours and the reaction solution was added ethyl acetate. After washing with water the organic layer was concentrated under reduced pressure and the residue was purified preparative thin-layer chromatography on silica gel (n-hexane:ethyl acetate=1:1). The purified product was concentrated under reduced pressure and to the residue was added 2 ml of 4n. solution of hydrogen chloride in ethyl acetate. The mixture was stirred at room temperature overnight and then stirred at 70°C for 1.5 hours. The mixture was concentrated under reduced pressure and the residue was purified preparative thin-layer chromatography on silica gel (n-hexane:ethyl acetate=1:1). The purified product was concentrated under reduced pressure and evaporated to dryness to obtain 27,1 mg (34,4% yield) of 5-{1-[3-(4-methylphenoxy)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione in sidebusting amorphous solid.

1H-NMR (DMSO-d6) δ ppm: of 2.0-2.2 (2H, m), of 2.28 (3H, s), 2,55-of 3.25 (5H, m), 3,68 (1H, DD, J1=3,7 Hz, J2=14.4 Hz), was 4.02 (2H, t, J=5,9 Hz), 4,14 (2H, t, J=7.0 Hz), 4,46 (1H, DD, J1=3,7 Hz, J2=10.5 Hz), 6,92 (2H, d, J=7.5 Hz), was 7.08 (1H, d, J=8.0 Hz), 7,05 to 7.4 (4H, m).

Example 1 preparation

1-Methyl-8-methoxy-5-(4-oxo-2-thioxo-5-thiazolidine)methyl-3,4-dihydro-1H-quinoline-2-he5 mg
Starch132 mg
Magnesium stearate18 mg
Lactose45 mg
Total200 mg

Tablets having the above composition is a tablet, made in the traditional way.

Example 2 preparation

1-(2-Phenylethyl)-8-methoxy-5-(4-oxo-2-thioxo-5-thiazolidine)methyl-3,4-dihydro-1H-quinoline-2-he5 g
Polyethylene glycol (molecular weight: 4000)0.3 g
Sodium chloride0.9 g
Monooleate of polyoxyethylenesorbitan 0.4 g
Metabisulphite sodium0.1 g
Methylparaben0.18 g
Propylparaben0.02 g
Distilled water for injection100 ml

The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water at 80°C under stirring. The resulting solution was cooled to 40°C and dissolved therein a compound of the present invention, the polyethylene glycol and monooleate of polyoxyethylenesorbitan. Then to the solution add additional distilled water, bringing the solution to a finite amount. The resulting solution is subjected to sterilization by filtration, using a suitable filter paper and the filtered solution was dispensed into 1 ml in ampoules, and thus, injection solutions.

Example 1 test

Promoting transcription activity of the tested compounds in relation to gene human TFF2 factor (hTFF2) evaluated reporter analysis of gene hTFF2.

(1) Obtaining reporter vector pGL3-hTFF2pro gene hTFF2

Was isolated DNA from HeLa cells (CCL-2, DAINIPPON PHARMACEUTICAL CO., LTD.), using the kit (DNeasy™ Tissue Kit, the manufacturer of firms who QIAGEN) for separation of deoxyribonucleic acid (DNA). Using extracted DNA as template, amplified promoter region hTFF2 using polymerase chain reaction (PCR). As amplificare PCR primers were selected oligomers 5'-CACGCGTCAGACTGGCAACCCCCTGTC-3' and 5'-GAAGCTTCTAGCTCAGCTGCACCCCAG-3', based on the message of Beck and others (Beck, S., Sommer P., Blin N., P. Gott, 5'-flanking motifs control cell-specific expression of trefoil factor genes (TFF), Int. J. Mol. Med. 2(3), 353-361 (1998)). As the DNA polymerase used Platinum® Pfx DNA polymerase. PCR was performed under conditions of denaturation for 30 seconds at 95°C, annealing for 30 seconds at 55°C and elongation for 75 seconds at 68°C, and the above procedure was repeated for 32 cycles.

PCR products were separated and purified by electrophoresis in 1% agarose gel and cloned in the vector pCR-BluntII-TOPO attached to the kit for cloning (Zero Blunt® TOPO® PCR Cloning Kit, manufacturer company Invitrogen Corporation). The obtained plasmid pCR-Blunt-TFF2pro was introduced inE. colifor transformation (TOP 10 Ultracomp™ Cells, the manufacturer company Invitrogen Corporation) and the strain transformant pCR-Blunt-TFF2pro/TOP10 selectively cultured in LB agar medium containing 30 μg/ml of Zeocin (Zeocin, manufacturer company Invitrogen Corporation). pCR-Blunt-TFF2pro/TOP10 were cultured with shaking using 50 ml of LB medium containing 30 μg/ml of Zeocin, at 37°C over night and got plasmid using the set to obtain plasmids (Concert™ High Purity Midiprep System, the manufacturer company GIBCO BR).

Determined nucleotide sequence of the PCR product cloned into plasmid pCR-Blunt-TFF2pro. A specific nucleotide sequence was compared with a copy of the promoter region hTFF2 registered in the Bank of genes (GenBank accession AB038162). Nucleotide sequence region MluI-HindIII, cloned into pCR-Blunt-TFF2pro, was identical to GenBank accession AB038162 (figure 1).

Figure 1 shows the top register of the nucleotide sequence and numbering of the nucleotides of the promoter region hTFF2 registered in GenBank (accession AB038162). The lower register shows the nucleotide sequence (see attached sequence number 1 in the list of sequences) PCR product cloned into the plasmid pCR-Blunt-TFF2pro. Underlined sections indicate the sequence (ACGCGT) recognition restriction enzymes MluI and sequence (AAGCTT) recognition restriction enzyme HindIII. Nucleotide sequence of the region MluI-HindIII identical between the promotor region hTFF2 registered in GenBank, and the PCR product cloned into plasmid pCR-Blunt-TFF2pro. Plot ATG, a prisoner in a cage, is a start codon broadcast, and the arrow shows the site of transcription initiation.

Plasmid pCR-Blunt-hTFF2pro were digested with restriction enzymes MluI and HindIII, was fractionally electrophoresis in 1% agarose gel and promotor region hTFF2 about what imali, using the kit for purification of nucleic acids (Concert™ Matrix Gel Extraction System manufactured by GIBCO BRL). Promotor region hTFF2 inserted into the region of the MluI-HindIII commercial plasmids pGL-Basic (produced by Promega Corporation)using a set of ligation (Ligation high produced by TOYOBO CO., LTD.), obtaining pGL3-hTFF2pro. Plasmid pGL3-hTFF2pro was introduced inE. colifor transformation (DH5α Competent Cell manufactured by TOYOBO CO., LTD.) and the strain of transformant pGL3-hTFF2pro/DH5α selectively cultured in LB agar medium containing 100 μg/ml ampicillin.

Strain pGL3-hTFF2pro/DH5α was inoculable in 2-liter Erlenmeyer flask containing 400 ml of LB medium containing 100 μg/ml ampicillin, and cultured with shaking at 200 rpm at 37°C on a rotary shaker device during the night. Plasmid pGL3-hTFF2pro were extracted and purified from culture cells using the set to obtain plasmids (EndoFree Plasmid Maxi Kit manufactured by QIAGEN).

Commercial vector pWLneo (produced by Stratagene)containing the marker of choice of drug, was introduced inE. colifor transformation (DH5α Competent Cell manufactured by TOYOBO CO., LTD.) and the strain of transformant pWLneo/DH5α selectively cultured in LB agar medium containing 100 μg/ml ampicillin. Strain pWLneo/DH5α was inoculable in 1-liter Erlenmeyer flask containing 150 ml of LB medium containing 100 μg/ml ampicillin, and cultiv is listed with shaking at 200 rpm at 37°C on a rotary shaker device during the night. Plasmid pWLneo were extracted and purified from culture cells using the set to obtain plasmids (EndoFree Plasmid Maxi Kit manufactured by QIAGEN).

(2) obtaining a cell line pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6-2 for reporter analysis of the gene hTFF2

A line of cancer cells of human gastric MKN-45 (JCRB0254, Health Science Research Resources Bank) were cultured in medium (IMDM medium)composed of 500 ml of medium (Iscove''s Modified Dulbecco's Medium manufactured by SIGMA), 50 ml of serum fetal cow (produced by SIGMA)immobilized by heating at 56°C for 30 minutes, 5 ml penicillin-streptomycin fluid (Penicillin-Streptomycin liquid manufactured by SIGMA) and 20 ml of 200 mm L-glutamine (produced by SIGMA), using a Cup for the cultivation of diameter 10 cm (CORNING Incorporated), placed in an incubator with 5% CO2at 37°C. Cells were washed with buffer (Dulbecco''s Phosphate Buffered Saline manufactured by SIGMA) and subjected to treatment with trypsin (0.25% Tripsin-1 mm EDTA·4Na manufactured by SIGMA) for suspension. Cells suspended in IMDM medium, were stained using Trypan Blue Stain, and 0.4% (trademark, Invitrogen Corporation), and counted the number of unstained cells as human cells, using hemocytometer. Cells were washed once with buffer (Dulbecco''s Phosphate Buffered Saline manufactured by SIGMA) and 106living cells suspended in the solution for gene transfer (0,25M mannitol/0.1 mm CaCl2/0.1 mm MgCl2/0.2 mm Tris-HCl, pH7,2-7,), to which was added 10 μg of the obtained plasmids pGL3-hTFF2pro and 2 μg plasmid pWLneo. The cell suspension is added plasmid was transferred into a 1 mm cuvette (produced by Bio-Rad Laboratories, Inc.) and introduced genes into cells by electroporation using the apparatus of SSH-1 (Shimadzu Corporation) to merge cells. Cells suspended in IMDM medium was inoculable in the Cup for the cultivation of 10 cm in diameter (CORNING Incorporated) and cultured in an incubator with 5% CO2at 37°C for 2 days. Then there was selective cultivation, using IMDM medium containing 400 μg/ml of Geneticin (Geneticin manufactured by Invitrogen Corporation). Then first was inoculable 100 µl of culture medium in each well of 96-hole tablet (produced by BD Falcon), and then expanded cells were subjected to passage cultivation in 24-hole tablet (produced by BD Falcon) and then 6-hole tablet (produced by BD Falcon) to obtain cells pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6. The obtained cells pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6 suspended in IMDM medium containing 400 μg/ml of Geneticin, inoculable in 96-well plate, using limiting dilution cloning, with a single clone of cells pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6-2. Cells pGL3-hTFF2proδ·pWL-neo/MKN-45 No. 6-2 proliferated in 10 cm Cup, collected and preserved by freezing.

(3) Reporter analysis of gene hTFF2 to use the cation cell line pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6-2

Cell line pGL3-hTFF2pro·pWL-neo/MKN-45 No. 6-2 thawed from the frozen state to apply. The cells were inoculable in IMDM medium containing 400 μg/ml of Geneticin, 10 cm Cup for cultivation and then passivatable every 3-5 days. During the passage of the cultivation, the cells were washed with buffer (Dulbecco''s Phosphate Buffered Saline manufactured by SIGMA) was added trypsin (0.25% of Tripsin-1 mm EDTA·4Na manufactured by SIGMA) to separate the cells for 5 minutes at 37°C. cell Suspension was collected by adding IMDM medium and stained cells using Trypan Blue Stain, and 0.4% (trademark, Invitrogen Corporation), and counted the number of unstained cells as living cells using hemocytometer. Confirmed cell survival 90% or higher before the living cells used for reporter analysis of the gene hTFF2.

The day before adding the tested compounds 100 ál of cell suspension, containing approximately 7.5×104cells were inoculable in each well of 96-well plates (produced by COSTAR) and cultured in an incubator with 5% CO2at 37°C. the Prepared compound having a concentration 200 times the final concentration, with dimethylsulfoxide (Wako Pure Chemical Industries, Ltd.). Compound with a given concentration were subjected to 100-fold dilution of IMDM medium and 100 μl of the diluted compounds were distributed in wells of 96-well plates. D is methylsulfoxide was diluted 100-fold IMDM medium and added to the wells, which have not been added compound. After addition of test compounds, cells were cultured in an incubator with 5% CO2at 37°C for 24 hours. After cultivation has removed the culture supernatant and 96-well tablets froze in the fridge deep freeze (produced by SANYO Electric Co., Ltd.). 96-well tablets were thawed at room temperature, when measured luciferase activity, and to each well was added 100 μl of PicaGene LT2.0 (Wako Pure Chemical Industries, Ltd.), twice divorced buffer (Dulbecco''s Phosphate Buffered Saline manufactured by SIGMA). The tablets were allowed to stand at room temperature for at least 30 minutes and measured the luciferase activity using a Labsystems Luminoskan (produced by ICN Biomedicals Inc.).

Taking the average dimension of the groups of holes with added dimethylsulfoxide in each tablet for 100%, calculate the percentage for each of the test compounds relative to the groups of holes with added dimethylsulfoxide (control %).

The results are shown in table 183.

Table 183 promoting products TFF2 activity 1000% or higher, and promoting products TFF2 activity of 300% or higher when the concentration of the tested compounds 10-6M is indicated as "+".

The above results show that mo is the concentration of the compounds of the present invention, providing promoting products TFF2 activity of 300% or higher, is less than 10-5M, more preferably less than 10-6M

Example 2 test

Therapeutic effects in models of rats with acetic acid induced ulcers of the stomach

Rats were fed with the previous day. Each rat was done by laparotomy under ether anesthesia and were isolated stomach. Then, using a single syringe were injected with 20 µl of a 30% solution of acetic acid in the submucosa at the junction of the body glandular stomach and privratnikovogo caves to create stomach ulcers.

(2) the Introduction of the tested compounds

Each test compound suspended in 0.5% solution of carboxymethylcellulose (CMC) at a concentration of 0.75 or 2.5 mg/ml Suspension was administered to rats orally once daily for 8 days, starting from the fourth day after surgery, with doses of 3 or 10 mg/kg For oral administration used the feeding tube and syringe. The volumes of each of the test compounds and vehicle (0.5% CMC) was 4 ml/kg

(3) Autopsy

The next day after the last injection the rats of media and test compounds rats were killed by exsanguination under ether anesthesia and removed every stomach. Retrieved stomachs were fixed in 1% formaldehyde for 15 minutes, cut along the greater curvature of the stomach to exposure ulcers and Merali area of ulceration.

(4) measuring the area of ulceration

The area of ulceration was measured under a stereo microscope (10×) with an eyepiece micrometer (1 mm2/cell grid) and calculated the ratio of recovery, in percent. The test results are shown in table 184. The ratio of the recovery percentage was calculated by the following formula:

Ratio rate (%)=the average area of ulceration in the control group-the average area of ulceration of the group entered the test connection×100
the average area of ulceration in the control group

Table 184 demonstrates that the compounds of the present invention is effective in the prevention and/or treatment of damage to the mucosa. img src="https://img.russianpatents.com/1090/10905475-s.jpg" height="191" width="102" />

1. Carbocyanine the connection represented by the General formula (1)

or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds;
where a represents a direct bond, lower alkylenes group or lower alkylidene group;
X represents an oxygen atom or a sulfur atom;
the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond;
R4and 5each represents a hydrogen atom, provided that when the bond between positions 3 and 4 barbastelle skeleton is a double bond, R4and R5instead, can be associated with each other in the form of a group-CH=CH-CH=CH-;
R1represents one of the following substituents (1-1)-(1-29):
(1-1) a hydrogen atom,
(1-2) a lower alkyl group,
(1-3) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of phenyl group, lower alkyl groups, lower alkoxygroup, halogen atoms, groups(B)1NR6R7, nitro, carboxypropyl, lower alkoxycarbonyl groups, cyanopropyl, phenyl(lower)alkoxygroup, fenoxaprop, piperidinyl(lower)alkoxycarbonyl groups, amino(lower)alkoxycarbonyl groups, optionally substituted by one or more3-C8cycloalkenyl groups, 2-imidazoledicarboxylic groups, substituted in the 2-imidazoline ring by one or more lower alkylthiophene, 3-pyrrolidinylcarbonyl groups, substituted at the 3-pyrrolinone ring by one or more lower alkyl groups, thiazolidinediones groups, substituted in thiazolidinone ring of the phenyl group, 3-azabicyclo[3.2.2]noninterpolating groups, piperidinyl(Issa)alkyl groups, the aniline(lower)alkyl groups, substituted in the amino group by one or more lower alkyl groups, phenylthio(lower)alkyl groups, indolyl(lower)alkyl groups and piperidinylcarbonyl groups, optionally substituted in piperidinium ring by one or more lower alkyl groups,
(1-4)3-C8cycloalkyl(lower)alkyl group,
(1-5) phenoxy(lower)alkyl group,
(1-6) naphthyl(lower)alkyl group,
(1-7) a lower alkoxy(lower)alkyl group,
(1-8) carboxy(lower)alkyl group,
(1-9) low alkoxycarbonyl(lower)alkyl group,
(1-10) pyridyl(lower)alkyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms; piperidinyl groups; morpholinopropan; piperazinilnom groups, optionally substituted in piperazinovom ring by one or more members selected from the group consisting of a phenyl group and lower alkyl group; thienyl group; phenyl group; peredelnyh groups; piperidinyl(lower)alkyl groups; phenylthio(lower)alkyl groups; biphenylene groups; (lower)alkyl groups, optionally substituted by one or more halogen atoms; pyridylamino; pyridylcarbonyl; lower alkoxygroup; aniline(lower)ALK is selected groups, substituted in the amino group by one or more lower alkyl groups; and inlinegroup, optionally substituted in the amino group by one or more lower alkyl groups,
(1-11) cyano(lower)alkyl group,
(1-12) group-A1-CONR8R9,
(1-13) a group of the following formula

(1-14) phenyl group,
(1-15) hinely(lower)alkyl group,
(1-16) lower alkoxy(lower)alkoxy-substituted lower alkyl group,
(1-17) replacement lower alkyl group,
(1-18) thiazolyl(lower)alkyl group, substituted in the thiazole ring by one or more members selected from the group consisting of halogen atoms, phenyl group, thienyl groups and peredelnyh groups,
(1-19) a lower alkyl group substituted by one or more atoms of halogen,
(1-20) lower alkylsilane(lower)alkyl group,
(1-21) phenoxy(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; halogen atoms; lower alkenyl groups; C3-C8cycloalkyl groups; nitro and phenyl groups,
(1-22) phenylthio(lower)alkyl group, substituted in finalromance one or more atoms of halogen,
(1-23) piperidinyl(lower)alkyl group, optionally substituted in piperidinium ring by one or more members selected from the group consisting of phenyl(lower)alkyl groups and phenyl groups,
(1-24) piperazinil(lower)alkyl group, optionally substituted in piperazinovom ring by one or more phenyl groups,
(1-25) 1,2,3,4-tetrahydroisoquinoline(lower)alkyl group,
(1-26) naphthyloxy(lower)alkyl group,
(1-27) benzothiazolinone(lower)alkyl group, optionally substituted in benzothiazoline ring by one or more alkyl groups,
(1-28) a lower alkyl group substituted by one or more members selected from the group consisting of chinalanoxin and ethanolammonium,
(1-29) pyridyloxy(lower)alkyl group, optionally substituted in the pyridine ring with one or more lower alkyl groups;
R2represents one of the following substituents (2-1)to(2-33):
(2-1) a hydrogen atom,
(2-2) the lower alkoxygroup,
(2-3) a lower alkyl group,
(2-4) carboxy(lower)alkoxygroup,
(2-5) the lowest alkoxycarbonyl(lower)alkoxygroup,
(2-6) a hydroxy-group,
(2-7) phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms is; the lower alkyl groups optionally substituted by one or more halogen atoms;
lower alkylthio, optionally substituted by one or more halogen atoms; lower alkoxygroup; nitro;
lower alkylsulfonyl groups; lower alkoxycarbonyl groups;
phenyl(lower)alkenyl groups; lower alkanoyloxy and 1,2,3-thiadiazolyl groups,
(2-8) piperidinyl(lower)alkoxygroup, optionally substituted in piperidinium ring by one or more lower alkyl groups,
(2-9) aminosilane lower alkoxygroup substituted by one or more lower alkyl groups,
(2-10) the lower alkenylacyl,
(2-11) pyridyl(lower)alkoxygroup, optionally substituted in the pyridine ring with one or more lower alkyl groups, each lower alkyl substituent optionally substituted by one or more atoms of halogen,
(2-12) the lower alkynylamino,
(2-13) phenyl(lower)alkyloxy,
(2-14) phenyl(lower)alkenylacyl,
(2-15) furyl(lower)alkoxygroup, optionally substituted in the furan ring by one or more lower alkoxycarbonyl groups,
(2-16) tetrazolyl(lower)alkoxygroup substituted in tetrazolium ring one member selected from the group consisting of phenyl groups, phenyl(neither the Shih)alkyl groups and C 3-C8cycloalkyl(lower)alkyl groups,
(2-17) 1,2,4-oxadiazolyl(lower)alkoxygroup substituted in 1,2,4-oxadiazole ring of the phenyl group, and a phenyl substituent substituted in the phenyl ring by one or more lower alkyl groups,
(2-18) isoxazolyl(lower)alkoxygroup substituted in isoxazoline ring by one or more lower alkyl groups,
(2-19) 1,3,4-oxadiazolyl(lower)alkoxygroup substituted in 1,3,4-oxadiazole ring of the phenyl group, and a phenyl substituent substituted in the phenyl ring by one or more lower alkyl groups,
(2-20) lower alkanoyl(lower)alkoxygroup,
(2-21) thiazolyl(lower)alkoxygroup substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more atoms of halogen,
(2-22) piperidinyloxy substituted in piperidinium the ring one or more benzoline groups, each bentely Deputy optionally substituted in the phenyl ring by one or more atoms of halogen,
(2-23) thienyl(lower)alkoxygroup,
(2-24) phenylthio(lower)alkoxygroup,
(2-25) carbamoylmethyl lower alkoxygroup, it is certainly substituted by one or more lower alkyl groups,
(2-26) benzoyl(lower)alkoxygroup,
(2-27) pyridylcarbonyl(lower)alkoxygroup,
(2-28) imidazolyl(lower)alkoxygroup substituted in the imidazole ring by one or more phenyl(lower)alkyl groups,
(2-29) phenoxy(lower)alkoxygroup,
(2-30) phenyl(lower)alkoxy-substituted lower alkoxygroup,
(2-31) 2,3-dihydro-1H-ingenjorsfirma,
(2-32) isoindoline(lower)alkoxygroup substituted in isoindoline the ring one or more exography,
(2-33) phenyl group;
R3represents one of the following substituents (3-1)to(3-19):
(3-1) a hydrogen atom,
(3-2) a lower alkyl group,
(3-3) replacement lower alkyl group,
(3-4) C3-C8cycloalkyl(lower)alkyl group,
(3-5) carboxy(lower)alkyl group,
(3-6) the lowest alkoxycarbonyl(lower)alkyl group,
(3-7) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; phenyl groups; lower alkoxycarbonyl groups; fenoxaprop; lower alkylthio; lower alkylsulfonyl groups; phenyl(lower)alkoxy the PP and amino groups, optionally substituted by one or more lower alkanolamine groups,
(3-8) naphthyl(lower)alkyl group,
(3-9) furyl(lower)alkyl group, substituted in the furan ring by one or more lower alkoxycarbonyl groups,
(3-10) thiazolyl(lower)alkyl group, substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and a phenyl group, each phenyl substituent substituted in the phenyl ring by one or more optionally halogen-substituted lower alkyl groups,
(3-11) tetrazolyl(lower)alkyl group, substituted in tetrazolium ring by one or more lower alkyl groups,
(3-12) benzothieno(lower)alkyl group, optionally substituted in benzothiophenes the ring one or more atoms of halogen,
(3-13) the lower alkylamino group,
(3-14) lower alkenylphenol group,
(3-15) phenyl(lower)alkenylphenol group,
(3-16) benzoimidazolyl(lower)alkyl group,
(3-17) pyridyl(lower)alkyl group,
(3-18) imidazolyl(lower)alkyl group, substituted in the imidazole ring by one or more phenyl(lower)alkyl groups,
(3-19) hinely(lower)alkyl group;
Represents a carbonyl group or a group-NHCO-;
1 is 0 or 1;
R6and R 7each independently represents one of the following substituents (4-1)-(4-79):
(4-1) a hydrogen atom,
(4-2) a lower alkyl group,
(4-3) the lower alkanoyloxy group,
(4-4) the lower alkylsulfonyl group, optionally substituted by one or more atoms of halogen,
(4-5) lower alkoxycarbonyl group, optionally substituted by one or more atoms of halogen,
(4-6) replacement lower alkyl group,
(4-7) pyridylcarbonyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of pyrrolidine groups and halogen atoms,
(4-8) pyridyloxy group substituted in the pyridine ring by one or more members selected from the group consisting of lower alkyl groups and lower alkoxygroup,
(4-9) pyridyl(lower)alkyl group,
(4-10) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms; fenoxaprop; lower alkoxygroup, optionally substituted by one or more halogen atoms; lower alkylthio; amino substituted by one or more members selected from the group consisting of lower alkyl is Rupp and lower alkanoyl groups; pyrrolidinyl groups, substituted in the pyrolidine ring one or more exography; piperidinyl groups, substituted in piperidinium ring by one or more lower alkyl groups; lower alkenyl groups; aminosulfonyl group; a hydroxy-group; carbamoyl groups substituted by one or more lower alkyl groups; phenyl(lower)alkoxygroup and ceanography,
(4-11)3-C8cycloalkyl group substituted in cycloalkene ring by one or more lower alkyl groups,
(4-12) benzoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; fenoxaprop; phenyl group; lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup; lower alkanoyl groups; nitro; ceanography; amino substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups; pyrrolidinyl groups, substituted in the pyrolidine ring one or more exography; pyrrolidine groups; pyrazolidine group; 1,2,4-triazolyl groups and imidazolinium groups,
(4-13) benzoyloxy group substituted in the phenyl ring by one or more lower alkyland what oxypropane,
(4-14)3-C8cycloalkylcarbonyl group,
(4-15) fuelleborni group,
(4-16) afterburning group,
(4-17) phenoxycarbonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, lower alkyl groups, halogen atoms and nitro,
(4-18) phenyl(lower)alkoxycarbonyl group substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and nitro,
(4-19) piperidinyloxy group, optionally substituted in piperidinium ring by one or more members selected from the group consisting of lower alkyl groups; lower alkanoyl groups; benzoline groups, optionally substituted in the phenyl ring by one or more halogen atoms; and phenyl groups, substituted phenyl ring one or more atoms of halogen,
(4-20) tetrahydropyranyl(lower)alkyl group,
(4-21)3-C8cycloalkyl(lower)alkyl group,
(4-22) lower alkenylphenol group,
(4-23) phenyl(lower)alkyl group, optionally substituted in the alkyl group by one or more lower alkoxycarbonyl groups and optionally substituted in the phenyl ring by one or more members selected from the group status is the present from halogen atoms, the lower alkyl groups optionally substituted by one or more halogen atoms, lower alkoxygroup, optionally substituted by one or more halogen atoms, and hydroxy-group,
(4-24) lower alkylenediamine phenyl(lower)alkyl group,
(4-25) furyl(lower)alkyl group,
(4-26) carbarnoyl(lower)alkyl group, substituted by one or more members selected from lower alkyl groups and a phenyl group, each phenyl substituent optionally substituted in the phenyl ring by one or more lower alkyl groups,
(4-27) lower alkoxy(lower)alkyl group,
(4-28) imidazolyl(lower)alkyl group, optionally substituted in the lower alkyl group by one or more members selected from the group consisting of carbamoyl group and lower alkoxycarbonyl groups,
(4-29) aminosilane lower alkyl group substituted by one or more lower alkyl groups,
(4-30) 2,3,4,5-tetrahydrofuryl group, substituted 2,3,4,5-tertrahydrofuran ring ring one or more exography,
(4-31) the lowest alkoxycarbonyl(lower)alkyl group,
(4-32) pyrrolidinyl(lower)alkyl group, optionally substituted in the pyrolidine ring by one or more lower alkyl groups,
(4-33) phenoxy(lower)alkane is safe group,
(4-34) morpholino(lower)alkyl group,
(4-35) indolenine group,
(4-36) thiazolidine group,
(4-37) 1,2,4-triazolyl group,
(4-38) pyridyl(lower)alkanoyloxy group,
(4-39) taylorsville group,
(4-40) thienyl(lower)alkanoyloxy group,
(4-41)3-C8cycloalkyl(lower)alkanoyloxy group,
(4-42) isoxazolecarboxylic group substituted in isoxazoline ring by one or more lower alkyl groups,
(4-43) pyrazinecarboxamide group,
(4-44) piperidinylcarbonyl group substituted in piperidinium ring by one or more members selected from bentilee group and lower alkanoyl groups,
(4-45) chromenickel group,
(4-46) isoindoline(lower)alkanoyloxy group substituted in isoindoline the ring one or more exography,
(About 4-47) diazolidinyl(lower)alkanoyloxy group substituted in thiazolidinone ring by one or more members selected from the carbonyl group and tocography,
(4-48) piperidinyl(lower)alkanoyloxy group,
(4-49) phenyl(lower)alkenylboronic group, optionally substituted in the phenyl ring by one or more atoms of halogen,
(4-50) phenyl(lower)alkenylboronic group substituted in the phenyl ring by one or more lower alkylenedioxy,
(4-51) pyridyl(lower)altercare the optimum group,
(4-52) pyridylthio(lower)alkanoyloxy group,
(4-53) indolocarbazole group,
(4-54) pyrrolidinedione group,
(4-55) pyrrolidinylcarbonyl group substituted in the pyrolidine ring one or more exography,
(4-56) benzofuranyl group,
(4-57) indolyl(lower)alkanoyloxy group,
(4-58) benzothiadiazole group,
(4-59) phenyl(lower)alkanoyloxy group, optionally substituted in the phenyl ring by one or more atoms of halogen,
(4-60) phenylsulfonyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxycarbonyl groups; ceanography; nitro; amino substituted by one or more alkanolamine groups; hydroxy-group; carboxyl group; a lower alkoxycarbonyl(lower)alkyl groups; halogen atoms; lower alkyl groups optionally substituted by one or more halogen atoms, and lower alkoxygroup, optionally substituted by one or more atoms of halogen,
(4-61) thienylmethyl group, optionally substituted in the thiophene ring by one or more members selected from the group consisting of halogen atoms and lower alkoxycarbonyl groups,
(4-62) henrylmoreno group,
(4-63) imidazolylalkyl g is the SCP, substituted in the imidazole ring by one or more lower alkyl groups,
(4-64) phenylsulfonyl group substituted in the phenyl ring by one or more lower alkylenedioxy,
(4-65) lower alkanesulfonyl group,
(4-66)3-C8cycloalkyl(lower)alkylsulfonyl group,
(4-67) of 3,4-dihydro-2H-1,4-benzocaineenthol group, a substituted 3,4-dihydro-2H-1,4-benzoxazinone ring by one or more lower alkyl groups,
(4-68) pyrazolylphenyl group, substituted in the pyrazol ring by one or more members selected from halogen atoms and lower alkyl groups,
(4-69) isoxazolecarboxylic group substituted in isoxazoline ring by one or more lower alkyl groups,
(4-70) triazolylmethyl group substituted in the thiazole ring by one or more members selected from the group consisting of lower alkyl groups and amino groups substituted by one or more lower alkanolamine groups,
(4-71) phenyl(lower)alkylsulfonyl group,
(4-72) phenyl(lower)alkanesulfonyl group,
(4-73) naphthalocyanine group,
(4-74) lower alkyloxyalkyl group,
(4-75) lower altneratively group,
(4-76) phenyl(lower)alkoxy-substituted lower alkoxycarbonyl group is,
(4-77)3-C8cycloalkylcarbonyl group substituted in cycloalkene ring by one or more lower alkyl groups,
(4-78) tetrazolyl group,
(4-79) isoxazolyl group substituted in isoxazoline ring by one or more lower alkyl groups; or
R6and R7can be connected to each other to form, together with the nitrogen atom to which they are attached, 1,2,3,4-tetrahydroisoquinoline group, isoindolyl group or a 5-7 membered saturated heterocyclic group, and heterocyclic group optionally contains one or more additional heteroatoms selected from S and N, and optionally substituted with one to three members from the following groups (5-1)-(5-28):
(5-1) lower alkyl groups,
(5-2) of the lower alkoxygroup,
(5-3) the carbonyl group,
(5-4) hydroxy-group,
(5-5) pyridyl(lower)alkyl groups,
(5-6) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; lower alkyl groups substituted by one or more halogen atoms; ceanography and hydroxy-group,
(5-7) low alkylenediamine phenyl(lower)alkyl groups,
(5-8) phenyl(lower)alkyl which groups, optionally substituted in the phenyl ring by one or more atoms of halogen,
(5-9) pyrimidinium groups,
(5-10) personilnya groups,
(5-11)3-C8cycloalkyl groups,
(5-12) phenyl(lower)alkoxygroup substituted in the phenyl ring by one or more atoms of halogen,
(5-13) benzoline groups, substituted in the phenyl ring by one or more atoms of halogen,
(5-14) benzoline groups, substituted in the phenyl ring by one or more lower alkylenedioxy,
(5-15) carbarnoyl(lower)alkyl groups substituted by one or more members selected from the group consisting of phenyl groups and lower alkyl groups,
(5-16) benzoxazolyl groups,
(5-17) lower alkoxycarbonyl groups,
(5-18) carbamoyl group,
(5-19) phenyl(lower)alkylidene groups, optionally substituted in the phenyl ring by one or more atoms of halogen,
(5-20) phenyl(lower)alkoxycarbonyl groups,
(5-21) peredelnyh groups, optionally substituted in the pyridine ring by one or more members selected from the group consisting of ceanography and lower alkyl groups,
(5-22) furyl(lower)alkyl groups,
(5-23) tetrahydropyranyl groups,
(5-24) imidazolyl(lower)alkyl groups,
(5-25) naftalina groups,
(5-26) 2,3-dihydro-1H-indanilnykh groups,
(5-27) 1,3-dioxol the Nile(lower)alkyl groups,
(5-28) groups(A3)mNR11R12;
A1represents the lowest alkylenes group;
R8and R9each independently represents one of the following substituents (6-1)-(6-25):
(6-1) a hydrogen atom,
(6-2) a lower alkyl group,
(6-3) phenyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkylthio; lower alkoxygroup, optionally substituted by one or more halogen atoms; halogen atoms; phenyl groups; lower alkylamino; ceanography; fenoxaprop; C3-C8cycloalkyl groups; pyrrolidinyl groups substituted by one or more exography; 1,2,3,4-tetrahydroisoquinolinium groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; 1,2,3,4-tetrahydroisoquinoline groups, optionally substituted by one or more lower alkyl groups; thiazolidine groups, optionally substituted by one or more phenyl groups; carbamoyl groups; phenyl(lower)alkoxygroup; lower alkylsulfonamides; inlinegroup, optionally substituted one and the multiple halogen atoms; phenyl(lower)alkyl groups and replacement of lower alkyl groups,
(6-4)3-C8cycloalkyl group,
(6-5)3-C8cycloalkyl(lower)alkyl group,
(6-6) carbarnoyl(lower)alkyl group,
(6-7) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; lower alkoxygroup, optionally substituted by one or more halogen atoms; halogen atoms and phenyl groups,
(6-8) lower alkyl substituted amino(lower)alkyl group,
(6-9) naftalina group,
(6-10) naphthyl(lower)alkyl group,
(6-11) tetrahydronaphthyl(lower)alkyl group,
(6-12) fluorenyl group,
(6-13) pyridyloxy group,
(6-14) pyridyl(lower)alkyl group,
(6-15) pyrimidinyl group,
(6-16) pyrazinyl(lower)alkyl group, substituted in pyrazinium ring by one or more lower alkyl groups,
(6-17) thiazolidine group,
(6-18) pyrazolyl(lower)alkyl group, substituted in the pyrazol ring by one or more lower alkyl groups,
(6-19) thienyl(lower)alkyl group
(6-20) piperidinyl group substituted in piperidinium ring by one or more States, using the data from the group consisting of lower alkyl groups; bentilee group and a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups,
(6-21) indolenine group,
(6-22) indazolinone group,
(6-23) 3,4-dihydroxybutyl, optionally substituted by one or more lower alkyl groups,
(6-24) pinolillo group, substituted by one or more lower alkyl groups,
(6-25) carbazolyl group, optionally substituted by one or more lower alkyl groups; or
R8and R9can be connected to each other to form, together with the nitrogen atom to which they are attached, 5-8-membered saturated heterocyclic group optionally containing one or more additional heteroatoms selected from S, O and N, and optionally substituted in the heterocyclic ring by one or more members selected from the group consisting of the following substituents (6-28-1)-(6-28-24):
(6-28-1) lower alkyl groups,
(6-28-2) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from
of halogen atoms and lower alkoxygroup, optionally substituted by one or more atoms of halogen,
(6-28-3) naphthas the l(lower)alkyl groups,
(6-28-4) phenyl(lower)allylcarbamate(lower)alkyl groups,
(6-28-5) phenylcarbamoyl(lower)alkyl groups,
(6-28-6) phenyl(lower)alkoxycarbonyl groups,
(6-28-7) phenoxy(lower)alkyl groups, substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups substituted by one or more atoms of halogen,
(6-28-8) biphenylene groups,
(6-28-9) phenyl group, optionally substituted in the phenyl ring by one or more atoms of halogen,
(6-28-10) 2,3-dihydroindole groups, optionally substituted by one or more atoms of halogen,
(6-28-11) benzothiazolyl groups, optionally substituted by one or more atoms of halogen,
(6-28-12) peredelnyh groups, optionally substituted by one or more atoms of halogen,
(6-28-13) benzothiazoline groups,
(6-28-14) benzothiazolyl groups,
(6-28-15) thienopyridine groups,
(6-28-17) phenyl(lower)alkoxygroup, optionally substituted in the phenyl ring by one or more atoms of halogen,
(6-28-18) fenoxaprop, optionally substituted by one or more atoms of halogen,
(6-28-19) benzoline groups, substituted in the phenyl ring by one or more members selected from halogen atoms and lower alkoxygroup,
(6-28-20) inlinegroup substituted in anilino ring by one or more lower alkyl groups, moreover, each lower alkyl substituent substituted by one or more atoms of halogen,
(6-28-21) inlinegroup substituted in the amino group by one or more lower alkyl groups and optionally substituted in the phenyl ring by one or more atoms of halogen,
(6-28-22) benzoperylene groups,
(6-28-23) naftalina groups,
(6-28-24) oxoprop; or
R8and R9can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered unsaturated heterocyclic group, and an unsaturated heterocyclic group optionally substituted in the heterocyclic ring by one or more members selected from the group consisting of the following substituents (6-29-1)-(6-29-3):
(6-29-1) phenyl groups optionally substituted by one or more atoms of halogen,
(6-29-2) 2,3-dihydroindole groups,
(6-29-3) benzothiazoline groups; or
R8and R9can be connected to each other to form, together with the nitrogen atom to which they are attached, 1,2,3,4-tetrahydroquinoline group; 1,2,3,4-tetrahydroisoquinoline group, 1,3-dihydroisoquinolines group; octahedral[1,2-a]personalni group substituted in pyrazinium ring by one or more lower alkyl groups, or 8-azabicyclo[3.2.1]octiles group, a substituted 8-AZ is bicyclo[3.2.1]octiles group of one or more phenoxypropane, with each peroxisomal substituted in the phenyl ring by one or more halogen atoms;
And2represents the lowest alkylenes group;
R10represents one of the following substituents (7-1)-(7-44):
(7-1) a hydrogen atom,
(7-2) a lower alkyl group,
(7-3) lower alkoxycarbonyl group, optionally substituted by one or more atoms of halogen,
(7-4) benzoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkyl groups optionally substituted by one or more halogen atoms; phenyl groups; halogen atoms; ceanography; fenoxaprop; lower alkoxycarbonyl groups; parasailing groups and lower alkoxygroup, optionally substituted by one or more atoms of halogen,
(7-5) lower alkanoyloxy group,
(7-6) phenyl(lower)alkanoyloxy group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups,
(7-7)3-C8cycloalkyl(lower)alkanoyloxy group,
(7-8) phenyl group, substituted phenyl ring by one or more lower alkyl groups,
(7-9) phenoxy(lower)alkanoyloxy group, optionally substituted in the phenyl to Lite one or more atoms of halogen,
(7-10) phenyl(lower)alkenylboronic group,
(7-11) pyridylcarbonyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent substituted by one or more atoms of halogen,
(7-12) fuelleborni group,
(7-13) taylorsville group,
(7-14) piperidinylcarbonyl group, optionally substituted in piperidinium ring by one or more lower alkanolamine groups,
(7-15) pyrrolidinylcarbonyl group, optionally substituted in the pyrolidine ring one or more exography,
(7-16) tetrahydropyranyloxy group,
(7-17) afterburning group,
(7-18) indolocarbazole group,
(7-19) benzofuranyl group,
(7-20) benzothiadiazole group, optionally substituted in benzothiophenes the ring one or more atoms of halogen,
(7-21) furyl(lower)alkyl group,
(7-22) pyridyl(lower)alkyl group, optionally substituted in the pyridine ring by one or more members selected from the group consisting of halogen atoms and lower alkyl groups, each lower alkyl substituent substituted by one or more atoms of halogen,
(7-23) thienyl(lower)alkyl which ing group, optionally substituted thiophene in the ring one or more atoms of halogen,
(7-24) phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of lower alkoxygroup, optionally substituted by one or more halogen atoms; ceanography; lower alkyl groups optionally substituted by one or more halogen atoms; amino groups substituted by one or more members selected from the group consisting of lower alkyl groups and lower alkanoyl groups; halogen atoms; lower alkoxycarbonyl groups; lower alkanoyloxy; lower alkylsulfonyl groups; lower alkylthio and pyrrolidinyl groups,
(7-25) thiazolyl(lower)alkyl group,
(7-26) imidazolyl(lower)alkyl group, substituted in the imidazole ring by one or more lower alkyl groups,
(7-27) pyrrolyl(lower)alkyl group, substituted in the pyrrole ring by one or more lower alkyl groups,
(7-28)3-C8cycloalkyl(lower)alkyl group,
(7-30) phenoxycarbonyl group substituted in the phenyl ring by one or more members selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxygroup,
(7-31) phenyl(lower)alkoxide manilow group, optionally substituted in the phenyl ring by one or more atoms of halogen,
(7-32) naphthalocyanine group,
(7-33) lower alkyloxyalkyl group,
(7-34)3-C8cycloalkylcarbonyl group,
(7-35) hinoklidilkarbinola group,
(7-36) group-CO-NR13R14,
(7-37) piperidinyl group substituted in piperidinium ring by one or more lower alkyl groups,
(7-38)3-C8cycloalkyl group,
(7-39) tetrahydropyranyloxy group,
(7-40) lower alkoxy(lower)alkyl group,
(7-41) tetrahydro-2H-cipirello group,
(7-42) naftalina group,
(7-43) biphenylene group,
(7-44) lower alkylsilane(lower)alkoxycarbonyl group;
And3represents the lowest alkylenes group;
m is 0 or 1;
R11and R12each independently represents one of the following substituents (8-1)to(8-5):
(8-1) a hydrogen atom,
(8-2) a lower alkyl group,
(8-3) lower alkanoyloxy group,
(8-4) phenyl(lower)alkanoyloxy group,
(8-5) phenyl group, substituted phenyl ring by one or more halogen atoms; or
R11and R12can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic group, optionally soda is containing one or more additional heteroatoms, selected from O and N, and the heterocyclic group optionally substituted by one to three members selected from the group consisting of the following substituents (9-1) and (9-2):
(9-1) lower alkyl groups,
(9-2) phenyl group; and
R13and R14each independently represents one of the following substituents (10-2)-(10-3):
(10-2) a lower alkyl group,
(10-3) phenyl group, or
R13and R14can be connected to each other to form, together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic group optionally containing one or more additional heteroatoms, selected from O and N.

2. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 1, where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond, and each of R4and R5represents a hydrogen atom.

3. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 2, where a group of the formula

where R3And X are as defined above in claim 1, attached in position 3, 4, 5, 6, 7 or 8 barbastelle is Caleta.

4. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 3, where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond, and a group of the formula

where R3And X are as defined above in claim 1, attached in position 5 or 6 barbastelle skeleton.

5. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 3 or 4, where a is a lower alkylenes group or lower alkylidene group.

6. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 5, where R1represents one of the substituents (1-2), (1-3), (1-4), (1-6), (1-10), (1-12), (1-13), (1-18) and (1-21)as defined above in claim 1.

7. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 6, where a group of the formula

where R3And X are as defined above in claim 1, attached in position 5 barbastelle skeleton.

8. Carbocyanine connection or Ecosol with conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 7, where R1is a phenyl(lower)alkyl group, optionally substituted in the phenyl ring by one or more members selected from the group consisting of phenyl rings, halogen atoms, groups
-(B)1NR6R7where1, R6and R7are as defined in claim 1, lower alkoxycarbonyl groups and phenyl(lower)alkoxygroup.

9. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds of claim 8, where a is a lower alkylenes group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

10. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 7, where a is a lower alkylenes group, R1represents a lower alkyl group, R2represents a hydrogen atom or a lower alkoxygroup,
R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

11. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or farmacevticheskijj main compounds according to claim 7, where a represents a lower alkylenes group, R1represents naphthyl(lower)alkyl group, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

12. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 7, where a is a lower alkylenes group, R1represents a group of the formula

where R10and a2are as defined above in claim 1, R2represents a hydrogen atom or a lower alkoxygroup, R3represents a hydrogen atom and X represents an oxygen atom or a sulfur atom.

13. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 3, where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and a group of the formula

where R3And X are as defined above in claim 1, attached in position 3, 4 or 5 barbastelle skeleton.

14. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids and pharmaceutically acceptable basic compounds indicated in paragraph 13 where R1represents one of the substituents (1-2) and (1-3)as defined in claim 1.

15. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds 14, where a represents a lower alkylenes group or lower alkylidene group, and R2represents a hydrogen atom or a lower alkoxygroup.

16. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 1, where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and R4and R5connected to each other in the form of a group-CH=CH-CH=CH-.

17. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to clause 16, where a group of the formula

where R3And X are as defined above in claim 1, attached in position 7 barbastelle skeleton.

18. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds 17, where R1represents one of the substituents (1-2) and (1-3)as defined above in claim 1.

19. Barbastelle the compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds p, where a represents a lower alkylenes group or lower alkylidene group, R2and R3both represent hydrogen atoms and X represents an oxygen atom or a sulfur atom.

20. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 1, where a is a direct link.

21. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 1, where a is a lower alkylenes group.

22. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to claim 1, where a is a lower alkylidene group.

23. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds according to any one of p-22, where the relationship between the clauses 3 and 4 barbastelle skeleton is a single bond or a double bond, and each of R4and R5represents a hydrogen atom.

24. Carbocyanine compound or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic the compounds according to any one of p-22, where the relationship between the clauses 3 and 4 barbastelle skeleton is a double bond and R4and R5connected to each other in the form of a group-CH=CH-CH=CH-.

25. Carbocyanine a compound selected from the group consisting of the following compounds:
5-[1-(biphenyl-4-ylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,
5-[1-(4-Chlorobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,
5-[1-(4-bromobenzyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,
5-[1-(2-naphthylmethyl)-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,
5-[1-(1-biphenyl-4-reparacin-4-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl]thiazolidine-2,4-dione,
5-{1-[1-(4-were)piperidine-4-ylmethyl]-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,
5-{1-[4-(2-chlorobenzenesulfonamide)benzyl]-8-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-ylmethyl}thiazolidine-2,4-dione,
1-(biphenyl-4-ylmethyl)-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,
8-methoxy-1-methyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,
8-methoxy-1-(3-methylbutyl)-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,
1-propyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,
1-isobutyl-8-methoxy-5-(4-oxo-2-thioxothiazolidin-ylmethyl)-3,4-dihydro-1H-quinoline-2-it,
8-methoxy-1-phenethyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it
1-(4-phenylthiomethyl)benzyl-5-(4-oxo-2-thioxothiazolidin-5-ylmethyl)-3,4-dihydro-1H-quinoline-2-it; or their salts with conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds.

26. Pharmaceutical composition having activity against the promotion of products TFF2, containing as an active ingredient carbocyanine compound according to claim 1 or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds.

27. Preventive and/or therapeutic agent used in the disorder, which improves the regulation of TFF has a preventive and/or therapeutic effect, containing as an active ingredient carbocyanine compound according to claim 1 or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds.

28. Preventive and/or therapeutic agent according to item 27, where disorder that increases regulation of TFF has a preventive and/or therapeutic effect, is a disease of the digestive tract, disease of the oral cavity, the disease of the upper respiratory tract, respiratory disorder, zabolevaniya, cancer or wound.

29. Preventive and/or therapeutic agent according to item 27, where disorder that increases regulation of TFF has a preventive and/or therapeutic effect, is an ulcer caused by the drug, peptic ulcer, ulcerative colitis, Crohn's disease, enteritis, caused by the drug, ischemic colitis, irritable bowel syndrome, ulcer developed after endoscopic diakonale, acute gastritis, chronic gastritis, reflux esophagitis, esophageal ulcer syndrome Beretta, gastrointestinal mucositis, hemorrhoidal disease, disease, Sjogren syndrome, xerostomia, rhinitis, pharyngitis, bronchial asthma, chronic obstructive pulmonary disease, dry eye or keratoconjunctivitis.

30. Preventive and/or therapeutic agent according to item 27, where TFF is a TFF2.

31. Application barbastelle compound according to claim 1 or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds for the manufacture of a prophylactic and/or therapeutic drugs used in disorders that increase regulation of TFF has a preventive and/or therapeutic effect.

32. The method of obtaining barbastelle connection (1) of the following formula:

or its salt with a conventional pharmaceutically acceptable acids
or pharmaceutically acceptable basic compounds, where R1, R2, R3, R4, R5X and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined in claim 1, and a represents a lower alkylenes group or lower alkylidene group, including:
(i) the interaction of the compound (2) formula:

or its salts, where R1, R2, R4, R5and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and R15represents a hydrogen atom or a lower alkyl group, and a4represents a direct bond or lower alkylenes group,
connection (3) formula:

or its salt, where R3and X are as defined above, to obtain the compounds (1A) of the formula:

or its salt with a conventional pharmaceutically acceptable acids
or pharmaceutically acceptable basic compounds, where R1, R2, R3, R4, R5, R15, A4and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above, and
(ii) the reduction of compound (1A), as defined above, or its salt with normal farm is citiesi acceptable acids or pharmaceutically acceptable basic compounds with obtaining the compound (1b) of the formula:

or its salt with a conventional pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds, where R1, R2, R3, R4, R5, R15, A4and the relationship between the clauses 3 and 4 barbastelle skeleton are as defined above.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where R is a group selected from: i) hydrogen; ii) phenyl and iii) thiophenyl; Z is a substituted or unsubstituted [1,3,4]thiadiazol-2-yl group, R1 is selected from: i) hydrogen; ii) straight C1-C6alkyl; iii) C6 or C10 aryl; iv) C(O)OR5; and v) 2-methylthiazol-4-yl; R5 denotes a straight or branched C1-C6alkyl; and index x equals 0 or 1. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent having human protein tyrosine phosphatase beta (HPTP-β) inhibiting action and use in treatment.

EFFECT: compounds can be used as human protein tyrosine phosphatase beta inhibitors.

11 cl, 1 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds have activity and selectivity towards the GABA A receptor subunit α5. In formula I , R1 denotes hydrogen, halogen, phenyl, a 6-member heterocycyl with 2 heteroatoms selected from N, O, a 5-member heteroaryl with 1-2 heteroatoms selected from S, N, cyano, lower alkyl, -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl or -(CH2)n-OH; equals 0, 1 or 2; R denotes hydrogen or lower alkyl; R2 denotes C3-C7-cycloalkyl, phenyl, 5-6-member heteroaryl with 1 heteroatom selected from N, S or a 9-10-member bicyclic heteroaryl with 1-3 heteroatoms selected from N, which are possibly substituted with one or more substitutes selected from a group comprising halogen, cyano, nitro, oxo group, lower alkyl, lower alkyl substituted with a halogen, lower alkoxy, lower alkoxy substituted with a halogen, -C(O)O-lower alkyl, lower alkylsulphonyl, -NRaRb, -C(O)-NRaRb, -C(O)-(6-member heterocyclyl with 2 heteroatoms selected from N, O), benzyloxy, 6-member heterocyclyl with 1-2 heteroatoms selected from N, S, O, possibly substituted with hydroxy, 1-2 oxo-groups, halogen or lower alkyl, or selected from a 5-6-member heteroaryl with 1-3 heteroatoms selected from N, possibly substituted with lower alkyl; Ra and Rb independently denote hydrogen, lower alkylsulphonyl, -C(O)H, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-S(O)2-lower alkyl, (5-member heteroaryl with 1 heteroatom selected from S)-sulphonyl, lower alkyl, -(CH2)n-(5-6-member heterocyclyl with 1 heteroatom selected from O, N), possibly substituted with lower alkyl, oxo group, or denotes -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(5-6-member heteroaryl with 1-2 heteroatoms selected from N), possibly substituted with an oxo group, -(CH2)n-OH, -(CO)-R', where R' denotes C3-C7-cycloalkyl, a 5-member heteroaryl with 1 heteroatom selected from S, or lower alkyl; R' denotes a phenyl or a 6-member heteroaryl with 1 heteroatom selected from N which are possibly substituted with a halogen or lower alkyl, optionally substituted with a halogen. The invention also relates to a medicinal agent containing one or more compounds of formula I and use of the disclosed compounds to prepare a medicinal agent.

EFFECT: high effectiveness of derivatives.

16 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R3 has any

of the formulae , where R1 is selected from

,

where each R2 independently denotes hydrogen, halogen, C1-C8alkyl, C1-C8alkoxy- C1-C8alkyl, C1-C8alkoxy; R4 denotes a five- or six-member monocyclic ring system, having two heteroatoms selected from O, N and S, such as pyrazinyl, isoxazole or thiazolyl, each of which can be optionally substituted with one or more of the following substitutes: C1-C8alkyl or C1-C8alkoxy; R5 and R6 independently denote hydrogen or C1-C8alkyl; R7 and R8 together form a cyclopentyl ring; R9 independently denotes C1-C8alkyl; R9a independently denotes C1-C8alkylcarbonyl or phenylcarbonyl; R10 denotes hydrogen; R11 independently denotes C1-C8alkyl or C1-C8alkoxy; R12 denotes hydrogen or -COOR17; R13 independently denotes hydrogen, phenyl and a 6-member heteroaryl containing one heteroatom selected from N; R17 denotes hydrogen; R23 denotes (a) C1-C8alkyl, phenyl, a 5-member heteroaryl containing 1-2 heteroatoms selected from S and N, where any phenyl or heteroaryl residue is optionally substituted with a halogen, C1-C8alkyl or C1-C8alkoxy; R24 denotes C1-C8alkyl; R27 denotes H, C1-C8alkyl, C1-C8alkoxy, O-phenyl, S-phenyl; R29 denotes -(CH2)w-COOR17; where w=0; R31 denotes hydrogen; and pharmaceutically acceptable salts thereof. The invention also relates to a method of producing the disclosed compounds, a pharmaceutical composition, having dual acting ATI and ETA receptor antagonist properties, containing the disclosed compound as an active component, use of the compound in preparing a medicinal agent and methods of treating arterial hypertension.

EFFECT: high effectiveness of the compounds.

8 cl, 1 dwg, 39 ex

FIELD: chemistry.

SUBSTANCE: compound of formula (I) has antiviral activity toward the human cytomegalovirus (HCMV) or some other representative of the Herpes virida group. In formula (I)

, R1 is a group of formula , where * denotes the point of bonding to a carbonyl group, R3 denotes a pyridyl which can be substituted with a substitute independently selected from a group comprising C1-C6alkyl or a cyano group, R5 and R6 independently denote hydrogen, R2 denotes a phenyl which can be substituted with a substitute selected from a group comprising a trifluoromethoxy group, a difluoromethoxy group and a monofluoromethoxy group, A is a group of formula

or , where * denotes the point of bonding to the carbonyl group, # denotes the point of bonding to the nitrogen atom of urea, R7 denotes C1-C6alkyl which can be substituted with a substitute selected from a group comprising C3-C6cycloalkyl, R8 and R9 independently denote hydrogen, halogen or C1-C6alkyl. The invention also relates to a method of producing a compound of formula (I) from a compound of formula , a method of producing a compound of formula (V), a medicinal agent containing the disclosed compound, use of the compound in preparing a medicinal agent and a method of fighting viral infections, among them human cytomegalovirus (HCMV) or some other representative of the Herpes viridae group.

EFFECT: high antiviral activity.

9 cl, 1 tbl, 39 ex

FIELD: chemistry.

SUBSTANCE: formula (I) compound has antibacterial activity and can be used as a medicinal agent. In formula ,

R1 is hydrogen, halogen, C1-4alkyl; R2 is selected from hydrogen, halogen, C1-4alkyl; R3 is selected from hydrogen, halogen, cyano, C1-4alkyl; W is -N(R6)-; X is a single bond; ring A is an unsaturated or partially saturated ring containing 5-6 atoms, one or two of which are independently selected from nitrogen and sulphur; or an unsaturated or partially saturated bicyclic ring containing 9-10 atoms, one, two or three of which are selected from nitrogen and sulphur; R4 and R5 are substitutes on a carbon atom and are independently selected from a halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, formyl, hydroxy iminomethyl, C1-4alkoxyminomethyl, C1-4alkyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkoxy)carbamoyl, N-(C1-4alkyl)-N-(C1-4alkoxy)carbamoyl, C1-4alkylS(O)a, where a equals 0-2, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C1-4alkylsulphonylamino, (saturated or unsaturated carbocycle containing 3-7 atoms)-R10- or (saturated, partially saturated or unsaturated ring containing 5-6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R11-; where R4 and R5 can independently and optionally substituted at the carbon atom with one or more R12; R6 is hydrogen; n equals 1-4; where values of R4 can be identical or different; m equals 0-4; where values of R5 can be identical or different; R12 is selected from azido, halogen, cyano, hydroxy, amino, carboxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkylS(O)a, where a equals 0-2, (saturated or unsaturated cabocycle containing 3-7 atoms)-R14- or (saturated, partially saturated or unsaturated ring containing 5 or 6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R15-; where R12 can independently and optionally be substituted at the carbon atom with one or more R9; R10, R11, R14 and R15 are independently selected from a single bond, -C(O)-, -N(R19)C(O)- or -C(O)N(R20)-; where R19 and R20 are independently selected from hydrogen or C1-4alkyl; R16 is selected from halogen, cyano, hydroxy, carboxy, methyl and methoxy. The invention also relates to a pharmaceutical composition, having antibacterial activity, containing the disclosed compound as an active ingredient, use of the disclosed compound to prepare a medicinal agent and a method of producing the compound of formula (I).

EFFECT: high activity of the compounds.

22 cl, 52 tbl, 721 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds of formula I: formula I or its pharmaceutically acceptable salt, where the radical values R3, R4, R2, X1, X2, R1 are such as presented in claim 1. Also, the invention describes a pharmaceutical composition exhibiting a Tec-family kinase inhibitor activity and based on the compounds of formula I, a method of Tec-family kinase activity inhibition, and a method of producing the compound of formula I.

EFFECT: produced and described new compounds which are effective as Tec-family (eg, Tec, Btk, Itk/Emt/Tsk, Bmx, Txk/Rlk) protein kinase inhibitors, and acceptable compositions are applicable for treatment or prevention of some diseases, disorders or conditions including but not limited, autoimmune, inflammatory, proliferative or hyperproliferative, or immunologically mediated diseases.

50 cl, 18 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

EFFECT: compounds of the invention exhibit properties of a glucokinase activator.

33 cl, 1499 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-alkylamides of formula I

, where A is selected from such groups as -CH2-CH2-, -CH2-CH2-CH2- and -Y-CH2-CH2-, where Y is selected from O, S and NR11 and Y is bonded to a Het group; Het denotes a 5-member or 6-member monocyclic aromatic group which contains one or two identical or different heterocyclic ring elements selected from N, NR13 and S, and which can be substituted with one or more identical or different substitutes R5; X denotes a single bond; R1 and R2 together with a N-CO group which contains them, form a 4-10-member monocyclic or bicyclic saturated or unsaturated ring which, besides a nitrogen ring atom which is part of the N-CO group, can contain one or two additional heterocyclic ring elements selected from N, NR12, O and S, which can be identical or different, provided that two ring elements from O and S cannot be in neighbouring positions in the ring, where the ring, formed by R1 and R2 and the N-CO group containing them, can be substituted with one or more identical or different substitutes R8; R3 is selected from phenyl, naphthalinyl and heteroaryl, which all can be substituted with one or more identical or different substitutes selected from a halogen atom, (C1-C4)alkyl, (C1-C4)alkyloxy group, which can be substituted with one or more fluorine atoms, (C1-C4)alkylamino, di((C1-C4)alkyl)amino, ((C1-C4)alkyl)-CONH-, CONH2, CN, CF3, H2NSO2- and (C1-C4)alkyl-SO2-; R5 is selected from a halogen atom and (C1-C4)alkyl; R8 is selected from a halogen atom, (C1-C4)alkyl and an oxo-group; R11 denotes a hydrogen atom; R12 is selected from a hydrogen atom and (C1-C4)alkyl; R13 is selected from a hydrogen atom and (C1-C4)alkyl; heteraryl is a 5-member or 6-member monocyclic aromatic group which contains one, two or three identical or different heterocyclic ring elements selected from N, NR13, O and S; in any of its stereoisomeric forms or mixture of stereoisomeric forms in any ratio, or its physiologically acceptable salt; provided that the -N(R2)-CO-R1 group cannot be an unsubstituted 2-oxopyrrolidin-1-yl group or unsubstituted 2-oxoimidazolin-1-yl group if the -N(R2)-CO-R1 group simultaneously denotes a group of formula

,

in which the bond through which the group is bonded to group A, is denoted by a line starting from position 2 of the pyridine ring, and in which R90 is selected from imidazol-1-yl, isoxazol-5-yl, isothiazol-5-yl, 1,2,4-thiazol-1-yl, pyrazin-2-yl and pyrazol-3-yl, which can all be substituted with (C1-C4)alkyl and which can be substituted in the pyridine ring with at most four substitutes selected from (C1-C4)alkyl and a halogen atom; and provided that the -N(R2)-CO-R1 cannot be a 1,3-dioxoisoindol-2-yl group of formula

in which the bond through which the group is bonded to group A is denoted by a line beginning from the nitrogen atom. The invention also relates to a method of producing said compounds, a pharmaceutical composition for stimulating endothelia NO synthase, as well as to use thereof in preparing a medicinal agent.

EFFECT: novel compounds which can be used in conditions where high expression of the said enzyme, high content of NO or normalisation of low content of NO is desired are obtained and described.

18 cl, 87 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I and to its pharmaceutically acceptable salts. In formula I , R1 means hydrogen or ; is specified from phenyl, and a 5-member heteroaromatic ring containing 1 to 2 heteroatoms specified inhe group consisting of sulphur and nitrogen; X is specified from lower alkylene, cyclisated lower alkylene containing 3 to 6 carbon atoms, and hydroxy(lower alkylene); R5 and R6 are independently specified in the group including hydrogen, lower alkyl, halogen and lower alkoxygroup; R3 is specified from hydrogen and -NH-R7; R4 is specified from hydrogen and -O(CH2CH2O)y-R10; R7 means lower alkyl; R10 means lower alkyl; n means an integer within 0 to 1; and y is equal to 0; provided when n is equal to 0, and R1 means hydrogen, then R3/R4 both cannot mean hydrogen. The invention also concerns a pharmaceutical composition containing a therapeutically effective amount of the compound under the invention.

EFFECT: preparation of the new compounds which show CDK1 kinase inhibiting activity and can be effective in cancer treatment, particularly breast cancer, lung cancer, colon cancer and prostate cancer treatment.

45 cl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I and to its pharmaceutically acceptable salts. In formula I , Y means -S- or -NH-; R1 is specified from hydrogen, -C(O)O-[CH2CH2O]P-R4, -C(O)-R3 and R2-(X)n-; R3 is specified from lower alkyl, cycloalkyl containing 3 to 6 carbon atoms and ; R4 means lower alkyl; X is specified from lower alkylene and cyclisated lower alkylene; R2 means ; where is specified from phenyl, and a 5 or 6-merous heteroaromatic ring containing 1 to 2 heteroatoms specified in the group consisting of sulphur and nitrogen; R5 and R6 are independently specified in the group including hydrogen, lower alkyl, halogen, perfluor (lower alkyl) and lower alkoxygroup; n means an integer within 1 to 2; and r means 0. The invention also concerns a pharmaceutical composition containing a therapeutically effective amount of the compound under the invention.

EFFECT: preparation of the new compounds which show CDK1 kinase inhibiting activity and can be effective in cancer treatment, particularly breast cancer, lung cancer, colon cancer and prostate cancer treatment.

64 cl, 27 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds which possess inhibiting properties with respect to PI3-kinase of general formula (1), where R1 is selected from group, including -NHRC, -NHC(O)Rc, -NHC(O)ORc, -NHC(O)NRcRc and -NHC(O)SRc, R2 stands for residue, optionally substituted with one or two substituents R4, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, 5-6-member heterocycloalkyl with one heteroatom, selected from nitrogen and sulphur, phenyl, benzyl and 5-6-member heteroaryl, including 1-2 nitrogen atoms, R3 stands for optionally substituted with one or several substituents Re and/or Rf residue, selected from group, including phenyl and 5-6-member heteroaryl with 1-3 heteroatoms, selected from nitrogen and oxygen, R4 represents residue, selected from group, including Ra, Rb, and substituted with one or several identical or different substituents Rc and/or Rb , Ra in each case is independently selected from group, including C1-C6alkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 9-member heteroaryl with one atom of nitrogen as heteroatom, Rb in each case is independently selected from group, including =O, -ORc, -NRCRC, halogen, -CF3, -CN, -S(O)Rc, -C(O)Rc, -C(O)ORc, -C(O)NRcRc, -C(O)N(Rg)NRcRc, -N(Rg)C(O)Rc, -N(Rg)S(O)2Rc, -N(Rg)S(O)2NRcRc, -N(Rg)C(O)ORc and -N(Rg)C(O)NRcRc, RC in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents R and/or Re residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, C6-C9aryl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-6-member heteroaryl with 1-2 heteroatoms, selected from nitrogen, oxygen and sulphur, Rd in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Re and/or Rf residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-10-member heteroaryl with one atom of nitrogen, Re in each case is independently selected from group, including =O, -ORf, -SRf, -NRfRf, -CN, -S(O)2Rf, -C(O)Rf, -C(O)ORf, -C(O)NRfRf and -OC(O)Rf, Rf in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Rg residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen and 5-6-member heteroaryl with one heteroatom, selected from nitrogen and sulphur, Rg in each case independently represents hydrogen, C1-C6alkyl, C3-C8cycloalkyl and 4-7-member heterocycloalkyl with one nitrogen as heteroatom, as well as to their pharmaceutically harmless acid-additive salts. Invention also relates to compounds, used as intermediate products of synthesis of formula (I) compounds, pharmaceutical composition and application of compounds for preparation of medication, possessing properties of PI3-kinase inhibitor.

EFFECT: elaborated are novel compounds, which possess properties of PI3-kinase inhibitor.

11 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 2-[(1Z)-1-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)methyl]-3,5-diphenyl-1,3,4-thiadiazol-3-ium chloride of formula I . The invention also relates to a method for synthesis of the said compound.

EFFECT: obtaining a novel chemical compound which can be used in synthesis of novel heterocyclic compounds and in medicine as a potential antibacterial agent.

2 cl, 1 dwg, 6 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) , where Z means where R means hydrogen, C4-C6cycloalkyl group attached either through one of ring carbon atoms, or through a lower alkylene group attached to the ring, or a linearly chained or branched lower alkyl group or a lower hydroxyalkyl group, or a lower aminoalkyl group, or a phenyl(lower alkyl) group optionally substituted with 1-2 substitutes chosen from lower alkyl, lower alkoxy, halogen and hydroxy, or heteroaryl(lower alkyl)group where heteroaryl is chosen from the group consisting from thienyl, substituted with lower alkyl group, imidazolyl, and thiazolyl substituted with the lower alkyl group; n means 0 or 1; or Z means a group where R means the lower alkyl group; X1 means methylene or NH group; and X2 means methylene; or X1 means methylene and X2 means methylene or a bond; or X1 means methylene, and X2 means O, S or a bond; Y1 means methylene, and Y2 means methylene, vinylene, ethylene, or a bond; Ar1 means unsubstituted or substituted phenyl; Ar2 means unsubstituted or substituted phenyl, unsubstituted or substituted thienyl, unsubstituted or substituted furyl, unsubstituted or substituted pyridyl; and when Ar1 and Ar2 are substituted, each Ar1 and Ar2 are independently substituted with one or more substituted chosen from lower alkyl, lower alkoxy, hydroxy, lower hydroxyalkyl, halogen, di- and trihaloalkyl, di- and trihaloalkoxy, mono- and dialkylamino, alkilthio, alkyl ester and nitro; provided that Ar1 and Ar2 do not simultaneously mean unsubstituted phenyl; W means oxygen or sulphur; or to their pharmaceutically acceptable salts; provided those specified in cl. 1 of the patent claim. Besides the invention concerns the compounds chosen from the group, to compounds of formula (I), to pharmaceutical compositions, to a method of inhibition of monoamine receptor activity, to a method of inhibition of monoamine receptor activation, to a method of treating a diseased state associated with serotonin receptor, to a method of treating schizophrenia, to a method of treating migraine, and also to a method of treating psychosis.

EFFECT: preparation of the new biologically active compounds capable to inhibit monoamine receptor activity.

65 cl, 140 ex, 5 tbl

Iap inhibitors // 2425838

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex

Up!