New esters of hydroximic acids and their pharmaceutical application

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.

EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.

29 cl, 746 ex, 6 tbl

 

The SCOPE of the INVENTION

This invention relates to new derivatives of esters, hydroxamic acids, intermediates and methods for their production, these compounds for use in therapy, pharmaceutical compositions comprising these compounds, methods of treating diseases, including introduction to the needy in this patient an effective amount of the compounds and use of these compounds in the manufacture of medicines.

BACKGROUND of the INVENTION

This invention relates to new compounds that can inhibit angiogenesis, i.e. which can inhibit the formation or development of new blood vessels. I believe that these compounds may be useful in the treatment of various diseases such as tumor diseases, in particular cancer.

Currently it is generally accepted that blocking angiogenesis around tumors may be an effective method of treatment of cancer, possibly as an auxiliary treatment. This is also reflected in the large number of research projects and clinical trials of angiogenesis inhibitors with any abscopal different approaches. Determined that currently, more than 300 drug candidates are in various stages of research [Matter, DDT, 6, 1005-1024, 2001]. Education new cravens what's vessels is a very complex process, you can plan a number of different ways. Therefore, drug candidates include inhibitors metalloprotease, inhibitors of the formation of vascular endothelial growth factor (VEGF), inhibitors of VEGF receptors, integrin antagonist, antibody, growth factor, and others

Of particular interest to the present invention are inhibitors of VEGF receptors, the most interesting inhibitors of receptor VEGFR-2 (KDR). Most clinically used inhibitor of VEGF receptors is semaxanib from Sugen, which recently discontinued in phase III studies. However, continued development of analogues of semaxanib. Another inhibitor of VEGF receptors, located on a clinical trial, is PTK-787 from Novartis, which recently entered phase III studies. Bilogo considers such inhibitors that are in clinical trials, Expert Opin. Investig. Drugs., 11, 737-745, 2002.

WO 01/29009 and WO 01/58899 describe derivatives of pyridine as tyrosine kinase inhibitors of VEGF receptors and VEGF-dependent proliferatio cells.

WO 02/090346 describes derivatives phthalazine as tyrosine kinase inhibitors of VEGF receptors with the angiogenesis-inhibitory activity.

WO 04/056806 describes the connection of 2-(1-H-indazol-6-ylamino)benzamide as inhibitors of protein kinases, which can be useful for the treatment of eye diseases.

PCT publication WO 00/2781, WO 00/27820, WO 01/55114, WO 01/81311, WO 01/85671, WO 01/85691, WO 01/85715, WO 02/055501, WO 02/066470, WO 02/090349, WO 02/090352, WO 03/000678, WO 02/068406, WO 03/040101 and WO 03/040102 describe amide derivatives of Anthranilic acid, which include compounds of the General structure A, receipt and use as tyrosine kinase inhibitors of VEGF receptors for the treatment of diseases associated with VEGF-dependent proliferatie cells.

The use of amide derivatives of Anthranilic acid for other therapeutic purposes disclosed previously, for example, in U.S. patent 3409668 (analgetic, anti-inflammatory agent, an antiulcer agent) and in EP 564356 (antagonist of angiotensin II).

PCT publication WO 02/06213 and WO 99/01426 describe derivatives substituted phenylaminopyrimidine acids include compounds of the General structure B as MEK inhibitors, pharmaceutical compositions and methods of use thereof.

U.S. patent 5155110 describes derivatives of hydroxamic acids having the properties of inhibition of cyclooxygenase and 5-lipoxygenase and pharmaceutical compositions for treating conditions that are favorable effect inhibition. The reference does not disclose tyrosinekinase inhibitory activity described derivatives of esters, hydroxamic acids.

SUMMARY of INVENTION

Allow the prevalence of the present invention unexpectedly discovered, the new class of esters, hydroxamic acid receptor shows high tyrosinekinase inhibitory activity on specific VEGF receptor, namely VEGFR-2, often referred to as the receptor KDR. New esters, hydroxamic acids of the present invention may have several advantages compared to known structurally related inorganic salts of Anthranilic acid. Compounds of the present invention may have improved pharmacokinetic and pharmacodynamic properties, such as improved solubility, absorption and metabolic stability compared to known structurally related inorganic salts of Anthranilic acid.

Thus, the invention concerns compounds of General formula I

where R1denotes hydrogen or linear, branched and/or cyclic, saturated or unsaturated hydrocarbon radical, optionally substituted by one or more substituents selected from the group comprising halogen, hydroxyl, amino, nitro and cyano;

D represents a nitrogen atom or C-R2;

E represents a nitrogen atom or C-R3;

F denotes a nitrogen atom or C-R4;

G represents a nitrogen atom or C-R5;

R2, R3, R4and R5are the same or different and individually represent water is od halogen, hydroxyl, amino, nitro, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, alkylsulfonyl, formyl, aminocarbonyl, alkylcarboxylic linear or branched, saturated or unsaturated hydrocarbon radical, optionally substituted by one or more substituents independently selected from the group comprising halogen, hydroxyl, amino, nitro, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, alkylsulfonyl, formyl, aminocarbonyl, alkylcarboxylic, or R2and R3or R3and R4or R4and R5together with the atoms to which they are attached, form a 5 - or 6-membered carbocyclic or heterocyclic ring;

W represents an oxygen atom, sulfur, two hydrogen atoms, =CH2, =N-O-R6or a group =N(R6);

R6denotes hydrogen, cycloalkyl, heteroseksualci, geteroseksualen, cycloalkenyl, aryl, heteroaryl, alkenyl, quinil or alkyl;

X and Y independently represent a radical of the formula -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)k-C(O)-(CH2)m-, -(CH2)n-, -(CH2)p-CH=CH-(CH2)q-, (CH 2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, -(CH2)w-C(O)-NH-(CH2)z-where i, j, k, m, n, p, q, r, s, t, u, w and z are equal integers from 0 to 6, and these radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;

R7denotes hydrogen, oxo, thioxo, halogen, hydroxyl, amino, imino, nitro, carboxy, carbarnoyl, cyano, cycloalkyl, alkyl, aryl, heteroaryl, heteroseksualci, geteroseksualen, heteroseksualci-heteroaryl, geterotsiklicheskikh, cycloalkenyl, alkenyl, quinil, alkoxy, alkoxyamino, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkenylboronic, alkoxycarbonyl, allylurea, allylthiourea, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, alkylsulfonyl, alkylsulfonyl, arylsulfonyl, formyl, aminocarbonyl, alkylcarboxylic, and these amino, imino, cycloalkyl, alkyl, aryl, heteroaryl, heteroseksualci, geteroseksualen heteroseksualci-heteroaryl, geterotsiklicheskikh, cycloalkenyl, alkenyl, quinil, alkoxy, alkoxyamino, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkenylboronic, alkoxycarbonyl, allylurea, allylthiourea, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, alkyls is phenylamino, alkylsulfonyl, arylsulfonyl, aminocarbonyl, alkylcarboxylic optionally are substituted by one or more substituents independently selected from the group comprising hydrogen, halogen, oxo, thioxo, hydroxyl, amino, imino, nitro, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, alkylsulfonyl, alkylsulfonyl, arylsulfonyl, aminocarbonyl, heteroarylboronic, formyl, aminocarbonyl, trifluoromethyl, alkylcarboxylic, heteroseksualci, geteroseksualen, aryl, allylurea, allylthiourea, heteroaryl, cycloalkyl, alkyl, cycloalkenyl, alkenyl, quinil and alkylaminocarbonyl;

B denotes aryl, heteroaryl, heteroseksualci, geteroseksualen, cycloalkyl or cycloalkenyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8;

R8denotes hydrogen, halogen, hydroxyl, amino, imino, oxo, thioxo, nitro, carboxy, cyano, alkoxy, phenoxy, alkylthio, alkoxycarbonyl, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, formyl, aminocarbonyl, allylurea, allylthiourea, is monocarbonate, alkylcarboxylic, geterotsiklicheskikh, heteroseksualci, geteroseksualen, aryl, heteroaryl, alkylaminocarbonyl and linear or branched, saturated or unsaturated hydrocarbon radical, and these amino, alkoxy, phenoxy, alkylthio, alkoxycarbonyl, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, aminocarbonyl, allylurea, allylthiourea, aminocarboxylate, alkylcarboxylic, geterotsiklicheskikh, heteroseksualci, geteroseksualen, aryl, heteroaryl, alkylaminocarbonyl and linear or branched, saturated or unsaturated hydrocarbon radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;

A denotes a linear, branched and/or cyclic, saturated or unsaturated hydrocarbon radical, heteroseksualci, geteroseksualen or heteroaryl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9;

R9denotes hydrogen, oxo, halogen, trifluoromethyl, hydroxyl, amino, nitro, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic alkoxycarbonyl, alkaluria, allylthiourea, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylboronic, alkylsulfonyl, formyl, aminocarbonyl, alkylcarboxylic, alkylaminocarbonyl, aminocarbonyl, heteroseksualci, geteroseksualen, heteroaryl and linear or branched, saturated or unsaturated hydrocarbon radical, and these amino, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, allylurea, allylthiourea, alkylsulphonyl, alkoxycarbonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylboronic, alkylsulfonyl, aminocarbonyl, alkylcarboxylic, alkylaminocarbonyl, aminocarbonyl, heteroseksualci, geteroseksualen, heteroaryl and linear or branched, saturated or unsaturated hydrocarbon radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;

and their pharmaceutically acceptable salt, hydrate or solvate;

provided that the connection is not

2-[(2-chloro-4-itfeel)amino]-4-fluoro-N-(2-hydroxyethoxy)-N-methylbenzamide,

2-[(2,6-dichloro-3-were)amino]-N-methoxy)-N-methylbenzamide,

2-[(2,6-dichlorophenyl)amino]-N-is hydroxy-N-methylbenzamide,

N-methoxy-2-[3-((E)-2-pyridin-2-elwenil)-1H-indazol-6-ylamino]benzamide,

N-isopropoxy-2-[3-((E)-2-pyridin-2-elwenil)-1H-indazol-6-ylamino]benzamide or

N-allyloxy-2-[3-((E)-2-pyridin-2-elwenil)-1H-indazol-6-ylamino]benzamide.

In another aspect, the invention concerns pharmaceutical compositions containing a compound of formula I or its pharmaceutically acceptable salt, hydrate or MES together with a pharmaceutically acceptable carrier or excipient.

In another aspect, the invention concerns a method of preventing, treating or alleviating diseases or conditions associated with unregulated angiogenesis, the method includes introducing an effective amount of the compounds of formula I need in this patient.

In another aspect of the invention concerns the use of compounds of formula I for the manufacture of a medicinal product for the prevention, cure or relief of diseases or conditions associated with deregulated angiogenesis, such as cancer.

In another aspect, the invention relates to intermediate compounds suitable for the synthesis of compounds of formula I, methods of preparing compounds of formula I and the above intermediate products.

BRIEF DESCRIPTION of DRAWINGS

The drawing shows the structure of the fused protein GST-KDR-cyt and GST-PLCy.

A. protein containing the intracellular domain(amino acids 793 at 1357) KDR and N-terminal attached to GST, designed for expression in insect cells Sf9.

B. protein containing two SH2 domain and two phosphorylation site (amino acids 541 on 797) and N-terminal attached to GST constructed and expressed in E. coli.

TM: transmembrane domain; GST: glutathione-S-transferase; SH2 domain of Src-homology 2; SH3 domain of Src-homology 3.

DETAILED description of the INVENTION

Definitions

Assume that the expression "hydrocarbon radical" means a radical containing only atoms of hydrogen and carbon, which may include one or more double and/or triple carbon-carbon bonds and contain cyclic fragments in combination with a branched or linear fragments. The specified hydrocarbon contains 1-20 carbon atoms and preferably contains from 1 to 12, for example 1-6, for example 1-4, for example 1-3, for example 1-2 carbon atoms. This expression includes alkyl, alkenyl, cycloalkyl, cycloalkenyl, quinil and aryl, which are listed below.

In this context implies that the term "alkyl" refers to a radical derived from a hydrocarbon removed one hydrogen atom. The specified alkyl contains 1-20, preferably 1-12, for example 2-6, for example 3-4 carbon atoms. This term includes the subclasses of normal Akilov (n-Akilov), secondary and tertiary Akilov, for example methyl, ethyl, n-propyl, isop the filing, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl and isohexyl.

It is implied that the term "cycloalkyl" denotes a saturated cycloalkenyl radical, including polycyclic radicals, for example, bicyclic, or tricyclic radical containing 3-20 carbon atoms, preferably 3-10 carbon atoms, in particular 3 to 8 carbon atoms, for example 3 to 6 carbon atoms, for example 4-5 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl and substituted.

It is implied that the term "cycloalkenyl" denotes a mono-, di-, tri - or tetradentate non-aromatic cyclic hydrocarbon radicals, including polycyclic radicals containing 3-20 carbon atoms, usually 3 to 10 carbon atoms, for example 3 to 6 carbon atoms, for example 4-5 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclo[2.2.1]heptenyl or bicyclo[4.1.0]heptenyl.

It is implied that the term "alkenyl" denotes a mono-, di-, tri-, Tetra - or pentanediamine hydrocarbon radical containing 2-10 carbon atoms, in particular 2 to 6 carbon atoms, for example of 2-4 carbon atoms, such as ethynyl, allyl, propenyl, butenyl, pentenyl, nonanol or hexenyl.

It is implied that the term "quinil" denotes a hydrocarbon Radik is l, containing 1-5 triple C-C bond and from 2 to 20 carbon atoms, alanovoy chain, usually containing 2-10 carbon atoms, in particular 2 to 6 carbon atoms, for example of 2-4 carbon atoms, such as ethinyl, PROPYNYL, butynyl, pentenyl or hexenyl.

It is implied that the term "heteroaryl" includes radicals consisting of heterocyclic aromatic ring, optionally condensed with carbocyclic rings or heterocyclic rings containing 1-6 heteroatoms (selected from O, S and N) and 1-20 carbon atoms, for example 1-5 heteroatoms and 1-10 carbon atoms, for example 1-5 heteroatoms and 1-6 carbon atoms, for example 1-5 heteroatoms and 1 to 3 carbon atoms, in particular 5 - or 6-membered rings with 1-4 heteroatoms, or 1-2 heteroatoms selected from O, S and N, or optionally condensed bicyclic rings with 1-4 heteroatoms, which at least one ring is aromatic, such as, for example, pyridyl, hinely, ethanolic, indolyl, tetrazolyl, thiazolyl, imidazolyl, imidazo[1,2-a]pyrimidinyl, pyrazolyl, oxazolyl, oxadiazolyl, thiophenyl, 1,2,4-triazolyl, isoxazolyl, pyrrolidinyl, thienyl, pyrazinyl, pyrimidinyl, [1,2,3]triazolyl, isothiazolin, tetrahydrofuranyl, imidazo[2,1-b]thiazolyl, benzimidazolyl, benzofuranyl, 2H-chromenes or benzofuranyl.

It is implied that the term "heteroseksualci" means the CEC is oakely radical, identified above, including polycyclic radicals, optionally condensed with carbocyclic rings containing 1-6 heteroatoms, preferably 1-3 heteroatoms selected from O, N or S, such as tetrahydropyranyl, morpholine, imidazolidine, benzo[1,3]dioxole or piperidinyl.

It is implied that the term "geteroseksualen" means cycloalkenyl radical, which is defined above, including polycyclic radicals, optionally condensed with carbocyclic rings containing 1-6 heteroatoms, preferably 1-3 heteroatoms selected from O, N or S, for example 1,6 - dihydropyridine, 2,3-dihydrobenzofuranyl, 4,5-dihydro-1H-[1,2,4]-triazolyl, 4,5-dihydrooxazolo, 1H-indazole, 1H-pyrazolyl or 4,5-dihydroisoxazole.

It is implied that the term "aryl" refers to a radical consisting of aromatic carbocyclic rings containing 6-20 carbon atoms, for example 6-14 carbon atoms, preferably 6-10 carbon atoms, in particular 5 - or 6-membered ring, optionally condensed carbocyclic rings, at least one aromatic ring, such as phenyl, naphthyl, anthracene, indenyl or indanyl.

The term "carbocyclic" includes aryl, cycloalkenyl and cycloalkenyl, which is defined above.

The term "heterocyclic" includes heteroaryl, heterotic alkyl and geteroseksualen, which is defined above.

It is implied that the term "halogen" denotes a Deputy from the 7th main group of the Periodic system, preferably fluorine, chlorine and bromine.

It is implied that the term "alkenylboronic" refers to a radical of the formula-O-C(O)-R, where R denotes alkenyl identified above, for example, acryloyloxy.

It is implied that the term "amino" means a radical of the formula-NR2where each R independently represents hydrogen, alkyl, alkenyl, cycloalkyl or aryl defined above, for example-NH2, AMINOPHENYL, methylamino, diethylamino, cyclohexylamino, -NH-phenyl, tert-butylamino or ethylamino.

It is implied that the term "imino" refers to a radical of the formula =N-R, where R denotes hydrogen or alkyl, which is defined above.

It is implied that the term "alkoxy" refers to a radical of the formula-OR, where R is alkyl or alkenyl defined above such as methoxy, ethoxy, n-propoxy, isopropoxy, butoxy and other

It is implied that the term "alkylthio" refers to a radical of the formula-S-R, where R is alkyl, as defined above.

It is implied that the term "alkoxycarbonyl" refers to a radical of the formula-C(O)-O-R, where R is alkyl, as defined above, such as methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and other

Units is Malaysia, the term "alkylcarboxylic" refers to a radical of the formula-O-C(O)-R, where R is alkyl, as defined above, for example, methylcarbonate or ethylcarbonate.

It is implied that the term "alkoxycarbonyl" refers to a radical of the formula-O-C(O)-O-R, where R is alkyl, as defined above.

It is implied that the term "alkylaryl" refers to a radical of the formula "-C(O)-R, where R is alkyl, as defined above, for example acetyl.

It is implied that the term "alkaluria" refers to a radical of the formula-NR'-C(O)-NH-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for hydrogen, alkyl or cycloalkyl defined above, for example-NH-C(O)-NH2macilwraith, amiloride, tert-butylurea, cyclohexylurea, methylthiourea, isopropylamino or n-propylurea.

It is implied that the term "allylthiourea" refers to a radical of the formula-NR'-C(S)-NH-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for hydrogen, alkyl or cycloalkyl defined above, for example-NH-C(S)-NH2.

It is implied that the term "alkoxycarbonyl" represents a radical of the formula-O-S(O)2-O-R, where R is alkyl, as defined above.

It is implied that the term "aminosulfonyl" refers to a radical of the formula

-S(O)2-NR2where each R, independent what about the denotes hydrogen, alkyl or aryl, which is defined above.

It is implied that the term "aminocarbonyl" refers to a radical of the formula-NR'-C(O)-O-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for alkyl, as defined above, such as aminocarbonyl-tert-butoxy.

It is implied that the term "alkylsulfonyl" refers to a radical of the formula-NR'-S(O)2-R, where R is alkyl, as defined above, and R' denotes hydrogen or alkyl, as defined above, for example, methylsulfonylamino.

It is implied that the term "arylsulfonyl" refers to a radical of the formula-NR'-S(O)2-R, where R is aryl, as defined above, and R' denotes hydrogen or alkyl, as defined above, for example, phenylcarbonylamino.

It is implied that the term "heteroarylboronic" refers to a radical of the formula-NR'-S(O)2-R, where R denotes heteroaryl, which is defined above, and R' denotes hydrogen or alkyl, as defined above, for example, thiazolecarboxamide.

It is implied that the term "alkoxyamino" refers to a radical of the formula =N-O-R, where R is alkyl, as defined above, for example, methoxyimino.

It is implied that the term "alkoxycarbonyl" refers to a radical of the formula-C(O)NR'-O-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for alkyl, which ODA is defined above.

It is implied that the term "aminocarbonyl" refers to a radical of the formula-C(O)-NR'2where each R' independently represents hydrogen, alkyl, alkenyl or aryl defined above, for example, carbarnoyl, methylaminomethyl, ethylaminomethyl, propylaminoethyl or butylaminoethyl.

It is implied that the term "alkylcarboxylic" refers to a radical of the formula-NR'-C(O)-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for alkyl, as defined above, for example acetylamino.

It is implied that the term "geterotsiklicheskikh" refers to a radical of the formula-NR'-C(O)-R, where R' denotes hydrogen or alkyl, as defined above, and R denotes heteroseksualci identified above, for example, pyrrolidinylcarbonyl.

It is implied that the term "arylsulfonyl" refers to a radical of the formula-NR'-S(O)2-R, where R' denotes hydrogen or alkyl, as defined above, and R stands for aryl, which is defined above.

It is implied that the term "arylsulfonyl" refers to a radical of the formula-S(O)2-R, where R stands for aryl, which is defined above.

It is implied that the term "alkylsulfonyl" refers to a radical of the formula

-S(O)2-R, where R is alkyl, as defined above, for example methylsulphonyl.

It is implied that the term "farmatsevticheskaia salt" refers to salts, obtained by the interaction of the compounds of formula I with a suitable inorganic or organic acid, such as hydrochloric, Hydrobromic, uudistoodetena, sulphuric, nitric, phosphoric, formic, acetic, 2,2-dichloracetic, adipic, ascorbic, L-aspartic, L-glutamic, galactosemia, lactic, maleic, L-malic, phthalic, citric, propionic, benzoic, glutaric, gluconic, D-glucuronic methansulfonate, salicylic, succinic, malonic, tartaric, benzolsulfonat, ethane-1,2-disulfonate, 2-hydroxyethanesulfonic acid, toluensulfonate, sulfamic or fumaric the acid. Pharmaceutically acceptable salts of compounds of formula I can also be obtained by the interaction with a suitable base, such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, silver hydroxide, ammonia or the like.

It is implied that the term "MES" means the class obtained by the interaction of the compounds, for example compounds of formula I and a solvent such as alcohol, glycerine or water, where the specified class is in solid form. If water is the solvent, then the specified class is referred to as a hydrate.

Preferred variants of the compounds of formula I

In a preferred present embodiment of the invention, W represents oxygen.

In each the m preferred embodiment of the invention R 1denotes hydrogen.

In another preferred variant of the invention, D represents C-R2E represents C-R3F denotes the C-R4and G represents C-R5.

In another preferred embodiment of the invention R2, R3, R4and R5denote hydrogen, chlorine, bromine, fluorine, methoxy or methyl.

In another preferred embodiment of the invention D is nitrogen, E represents C-R3F denotes the C-R4and G represents C-R5.

In another preferred embodiment of the invention R3, R4and R5denote hydrogen.

In another preferred variant of the invention, D represents C-R2E represents nitrogen, F denotes the C-R4and G represents C-R5.

In another preferred embodiment of the invention R2, R4and R5denote hydrogen.

In another preferred embodiment B represents phenyl or pyridyl, for example 2-pyridyl, 3-pyridyl or 4-pyridyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8.

In another embodiment, B denotes naphthyl, 2,3-dihydrobenzofuranyl, benzofuranyl, 2H-chromenes, thiazolyl, 4,5-dihydro-1H-[1,2,4]-triazolyl, tetrahydropyranyl, 1,6-dihydropyridine, imidazolyl, imidazolidinyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-a]is rimidine, 1,2,4-triazolyl, piperidinyl, pyrrolidinyl, 4,5-dihydrooxazolo, isoxazolyl, 4,5-dihydroisoxazole, pyrimidinyl, 1H-pyrazolyl, 1H-indazol-6-yl, chinolones or ethanolamines, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8.

In another embodiment, B represents 1H-indazol-6-yl, substituted at the 3 position by one Deputy, is independently selected from the group consisting of R8and specified 1H-indazol-6-yl optionally is optionally substituted by one or more substituents independently selected from the group consisting of R8.

In another preferred embodiment, R8denotes hydrogen, halogen, alkoxy, phenoxy, alkoxycarbonyl, carboxy, aminocarbonyl, cyano, alkyl, oxo, hydroxy, amino, heteroseksualci, geteroseksualen, alkylsulfonyl, alkylsulfonyl, allylurea, allylthiourea, alkylcarboxylic, geterotsiklicheskikh or aminocarboxylate where specified alkoxy, phenoxy, alkoxycarbonyl, alkoxycarbonyl, aminocarbonyl, alkyl, amino, heteroseksualci, alkylsulfonyl, alkylsulfonyl, allylurea, allylthiourea, alkylcarboxylic, geterotsiklicheskikh or aminocarbonyl optionally is substituted one or more is their deputies, independently selected from the group consisting of R7.

In another preferred embodiment, R8denotes hydrogen, fluorine, chlorine, bromine, cyano, carboxy, oxo, -NH2, hydroxy, methoxy, phenoxy, methoxycarbonyl, etoxycarbonyl, methoxycarbonyl, methylaminomethyl, pyrrolidinylcarbonyl, ethylaminomethyl, propylaminoethyl, butylaminoethyl, methyl, ethyl, propyl, morpholine, pyrrolidine, methylsulfonylamino, methylsulphonyl, macilwraith, amiloride, tert-butylurea, cyclohexylurea, methylthiourea, isopropylamino, n-propylurea, methylamino or ethylamino where specified methoxy, phenoxy, methoxycarbonyl, etoxycarbonyl, methoxycarbonyl, tert-butoxycarbonyl, methylaminomethyl, pyrrolidinylcarbonyl, ethylaminomethyl, propylaminoethyl, butylaminoethyl, methyl, ethyl, propyl, morpholine, pyrrolidine, methylsulfonylamino, methylsulphonyl, macilwraith amiloride, tert-butylurea, cyclohexylurea, methylthiourea, isopropylamino, n-propylurea, methylamino or ethylamino optionally is substituted by one or more substituents independently selected from the group consisting of R7.

In another embodiment, X and Y independently denotes a radical of the formula -(CH2)iNH-C(O)-(CH2)j, -(CH2)k-C(O)-(CH2)m-, -(CH2/sub> )n-, -(CH2)p-CH=CH-(CH2)q-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, -(CH2)w-C(O)-NH-(CH2)z-where i, j, k, m, n, p, q, r, s, t, u, w and z are equal integers from 1 to 5, for example from 2 to 4 or 3, where these radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;

In another preferred embodiment X is a bond, -CH2-, -(CH2)2-, -CH(CH3)-, -C(O)-, -C(O)-CH2-, -(CH2)2-O-CH2- or-CH=CH-.

In another preferred embodiment Y represents a radical of the formula -(CH2)iNH-C(O)-(CH2)j-where i is an integer from 1 to 4 and j is 0; or Y denotes a radical of the formula -(CH2)n-, where n is an integer from 0 to 6; or Y denotes a radical of the formula -(CH2)p-C(O)-NH-(CH2)qwhere p is an integer from 0 to 6 and q is 0; or Y denotes a radical of the formula -(CH2)r-O-(CH2)Swhere r is an integer from 0 to 6 and s is an integer from 0 to 1; or Y denotes a radical of the formula -(CH2)t-NH-(CH2)u-where t is an integer from 0 to 4; u is an integer from 0 to 1; where these radicals optionally are substituted by one or more substituents independently selected from the group, with the standing of R 7.

In particular, Y represents a bond, -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-O-, -(CH2)2-O-CH2-, -(CH2)3-O-CH2-, -(CH2)3-NH-C(O)-, -(CH2)4-NH-C(O)-, -CH2-CH(OH)-CH2-O-, -(CH2)2-NH-CH2-, -(CH2)4-NH-CH2-, -CH2-CH2-CH2-, -CH2-C(O)-, -CH2-C(O)-NH - or-CH(CH2NHSO2CH3)-.

In another preferred embodiment, A means (C6-C10)aryl, (C3-C10)heteroseksualci, (C3-C10)cycloalkyl, (C3-C6)cycloalkenyl, (C2-C5)alkenyl, (C1-C6)alkyl, (C2-C10)heteroaryl, geteroseksualen or toluyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9.

In another preferred embodiment, A represents methyl, ethyl, (C6)aryl, (C9)aryl, (C10)aryl, (C14)aryl, (C3)alkyl, (C4)alkyl, (C5)alkyl, (C2)alkenyl, (C3)alkenyl, (C4)alkenyl, (C5)alkenyl, (C3)cycloalkyl, (C4)cycloalkyl, (C5)cycloalkyl, (C6)cycloalkyl, (C7)cycloalkyl, (C8)cycloalkyl, (C10)cycloalkyl, (C6)cycloalkenyl, (C3)heteroaryl, (C4)heteroaryl, (C5)heteroaryl is, (C6)heteroaryl, (C7)heteroaryl, (C9)heteroaryl, (C4)heteroseksualci, (C5)heteroseksualci, (C3)geteroseksualen, (C4)geteroseksualen, (C5)geteroseksualen or toluyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9.

In particular, A represents methyl, ethyl, allyl, butenyl, phenyl, thiazolyl, pyridyl, tert-butyl, propyl, pentyl, isobutyl, benzo[1,3]dioxole, indanyl, naphthyl, anthracene, thiazolyl, thiophenyl, oxadiazolyl, isoxazolyl, cyclopropyl, cyclobutyl, [1,2,3]triazolyl, cyclopentyl, cyclohexyl, cyclohexenyl, substituted, bicyclo[2.2.1]heptenyl, bicyclo[2.2.1]heptyl, bicyclo[4.1.0]heptenyl, cycloheptyl, cyclooctyl, chinoline, tetrahydropyranyl, 4,5-dihydrooxazolo or tetrahydropyranyl that all optionally are substituted by one or more substituents independently selected from the group consisting of R9.

In another preferred embodiment, R9denotes hydrogen, nitro, halogen, oxo, cyano, trifluoromethyl, carboxy, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkenyl, quinil, alkylthio, heteroseksualci, geteroseksualen, heteroaryl, amino, arylsulfonyl, allylthiourea, allylurea, heteroarylboronic, alkyls is phenylamino, aminocarbonyl, aminocarbonyl, aryl, where the specified alkoxycarbonyl, alkyl, cycloalkyl, alkenyl, quinil, alkylthio, heteroseksualci, heteroaryl, amino, arylsulfonyl, allylthiourea, allylurea, heteroarylboronic, alkylsulfonyl, aminocarbonyl, aminocarbonyl or aryl, optionally is substituted by one or more substituents independently selected from the group consisting of R7.

In particular, R9denotes hydrogen, nitro, fluorine, chlorine, bromine, iodine, oxo, cyano, carboxy, ethynyl, ethinyl, PROPYNYL, butynyl, methoxy, aminomethyl, aminoethyl, AMINOPHENYL, morpholine, carbomethoxy, cyano, trifluoromethyl, methyl, tert-butoxy, ethyl, propyl, butyl, pentyl, cyclopentyl, nonanal, methylsulfanyl, aminocarbonyl-tert-butoxy, methylsulfonylamino, thiazolecarboxamide, phenylcarbonylamino, -NH-C(S)-NH2, -NH-C(O)-NH2morpholinyl, ethylaminomethyl, thiophene, amino or phenyl, where the specified ethynyl, ethinyl, PROPYNYL, butynyl, methoxy, ethoxy, aminomethyl, aminoethyl, morpholine, carbomethoxy, cyano, trifluoromethyl, methyl, ethyl, propyl, butyl, pentyl, cyclopentyl, nonanal, methylsulfanyl, methylsulfonylamino, thiazolecarboxamide, phenylcarbonylamino, -NH-C(S)-NH2, -NH-C(O)-NH2morpholinyl, ethylaminomethyl, thiophene, amino or phenyl optionally are substituted by one or is more substituents, independently selected from the group consisting of R7.

In one embodiment, the B-R8represents 4-pyridyl, 4-forfinal or 4-methoxyphenyl.

In one embodiment, the A-R9represents 2-nitrophenyl, 4-nitrophenyl, 3-triptoreline, 2-triptoreline, 4-triptoreline, 3-methoxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,3-dichlorophenyl, 3,6-dichlorophenyl, 2-forfinal, 3-forfinal, 4-forfinal, 6-fluoro-2-chlorophenyl, 4-fluoro-2-chlorophenyl, 2-fluoro-3-chlorophenyl, 4-carbomethoxybiphenyl, 4-cyanophenyl, quinoline-2-yl, phenyl, 2-methylthiazole-4-yl or 4-methoxyphenyl.

In another preferred embodiment, R7denotes hydrogen, halogen, hydroxy, carboxy, carbarnoyl, cyano, oxo, thioxo, aryl, alkyl, alkoxy, arylsulfonyl, aminocarbonyl, heterocyclisation, heteroseksualci, heteroaryl, geteroseksualen, alkoxycarbonyl, alkoxy, imino, alkoxyimino, alkylcarboxylic, alkenylboronic, cycloalkyl or amino, where the specified aryl, alkyl, alkoxy, alkoxyamino, arylsulfonyl, aminocarbonyl, heterocyclisation, heteroseksualci, heteroaryl, geteroseksualen, alkoxycarbonyl, alkoxy, imino, alkylcarboxylic, alkenylboronic, cycloalkyl or amino optionally is substituted one or not is how many deputies, independently selected from the group comprising halogen, alkenylacyl, hydroxy, cyano, amino, alkylcarboxylic, alkylcarboxylic, alkyl, alkoxy, aryl or oxo.

In particular, R7denotes hydrogen, hydroxy, amino, -NH2diethylamino, cyclohexylamino, tert-butylamino, oxo, thioxo, phenyl, pyridyl, acetylamino, chlorine, methyl, ethyl, propyl, butyl, morpholine, methoxy, tert-butoxy, cyclopropyl, hydroxyethyl, methoxyimino, -NH-phenyl, TRIFLUOROACETYL, acetyl, ethoxy, 2-acetylamino-4-methylthiazole, tert-butyl, methylpiperazine, 2-hydroxyethylpiperazine, methylthiazole, hydroxypyrrolidine, dimethylamino, toluyl, trifluoromethyl, methylamino, pyrrolidin, methoxycarbonyl, etoxycarbonyl, carboxy, carbarnoyl, cyano, methylcarbonate, ethylcarbonate, acryloyloxy, cyclopropyl or 2.5-dioxoimidazolidin.

In one embodiment, the A-R9represents 2-nitrophenyl, 4-nitrophenyl, 3-triptoreline, 2-triptoreline, 4-triptoreline, 3-methoxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,3-dichlorophenyl, 3,6-dichlorophenyl, 2-forfinal, 3-forfinal, 4-forfinal, 6-fluoro-2-chlorophenyl, 4-fluoro-2-chlorophenyl, 2-fluoro-3-chlorophenyl, 4-carbomethoxybiphenyl, 4-cyanophenyl, quinoline-2-yl, phenyl, 2-methylthiazole-4-yl or 4-methoxyphenyl.

Another preference is sustained fashion option B is 4-pyridyl, optionally substituted in position 2 by the radical R8or B denotes a phenyl, optionally having up to two substituents R8the same or different.

In another preferred embodiment, A represents 1-phenyl substituted in position 4 by bromine, fluorine, stands or chlorine, optionally additionally substituted by one or more substituents independently selected from the group consisting of R9.

In another preferred embodiment, A is a hydrocarbon radical containing 5 - or 6-membered carbocyclic ring, where the specified hydrocarbon moiety optionally is substituted by one or more substituents independently selected from the group consisting of R9.

In another preferred embodiment, A represents phenyl, substituted by at least one fluorine, optionally additionally substituted by one or more substituents independently selected from the group consisting of R9.

In another preferred at present embodiment, compounds of General formula I have a molecular weight below 1300 daltons, for example below 900 daltons, for example below 800 daltons, for example below 700 daltons, for example less than 600 daltons, for example less than 500 daltons.

In another preferred at present embodiment, A has no more than two substituents independently selected from the group consisting of R9other than hydrogen.

In another preferred at present embodiment, B has no more than two substituents, independently selected from the group consisting of R8other than hydrogen.

In particular, the compounds of formula I can be selected from the list including:

N-benzyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 1),

N-(4-nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 2),

N-(2-nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 3),

2-[(pyridine-4-ylmethyl)amino]-N-(3-triftormetilfosfinov)benzamide (compound 4),

2-[(pyridine-4-ylmethyl)amino]-N-(2-triftormetilfosfinov)benzamide (compound 5),

N2-[(pyridine-4-ylmethyl)amino]-N-(4-triftormetilfosfinov)benzamide (compound 6),

N-(4-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 7),

N-(3-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 8),

2-[(pyridine-4-ylmethyl)amino]-N-(3,4,5-trimethoxybenzoate)benzamide (compound 9),

N-(4-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 10),

N-(3-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 11),

N-(2-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 12),

N-(2-bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 13),

N-(2,4-dichloraniline)-2-[(feast of the DIN-4-ylmethyl)amino]benzamide (compound 14),

N-(3,4-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (connection

15),

N-(2,6-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 16),

N-(3,5-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 17),

N-(2,3-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 18),

N-(2,5-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 19),

N-(2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 20),

N-(3-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 21),

N-(4-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 22),

N-(2-chloro-6-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 23),

N-(2-chloro-4-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 24),

N-(3-chloro-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 25),

methyl ester of 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 26),

N-(4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 27),

2-[(pyridine-4-ylmethyl)amino]-N-(quinoline-2-ylethoxy)benzamide (compound 28),

n-phenoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 29),

N-(2-phenoxyethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 30),

N-(3-phenylpropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 31),

N-(methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 32),

N-benzyloxy-2-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 33),

2-(4-forbindelsen)-N-(4-methoxybenzyloxy)nicotinamide (compound 34),

2-(4-methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 35),

N-(4-cianfrocca)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 36),

N-(4-bromophenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 37),

N-(4-fluoro-2,6-dimethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 38),

N-(4-fluoro-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 39),

N-(2,3-debtor-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 40),

N-(3-fluoro-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 41),

N-(5-fluoro-2-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 42),

2-[(pyridine-4-ylmethyl)amino]-N-(2,3,5,6-titrator-4-methoxybenzyloxy)benzamide (compound 43),

N-(4-bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 44),

N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 45),

N-(3-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 46),

N-(4-Methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 47)

N-[2-(3,3-Dimethylbutan-1-enyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 48),

2-[(pyridine-4-ylmethyl)amino]-N-(2-streventname)benzamide (connect the tion 49),

N-[3-(3-hydroxyprop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 50),

N-[3-(5-CANopen-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 51),

N-[2-(3-hydroxyprop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 52),

2-[3-(2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}phenyl)prop-2-ynyloxy]

ethyl ester of acetic acid (compound 53),

N-[2-(3-methyl-3H-imidazol-4-ylethynyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 54),

N-[3-(3-methyl-3H-imidazol-4-ylethynyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 55),

N-(2-cyanomethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 56),

N-(2-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 57),

N-(4-hydroxymethylbenzene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 58),

N-(4-fluoro-2-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 59),

N-(2-fluoro-6-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 60),

N-(4-fluoro-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 61),

N-(4-methyl-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 62),

N-(4-methoxy-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 63),

N-(2-methoxybenzyl the XI)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 64),

N-(4-interoceanica)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 65),

2-[(pyridine-4-ylmethyl)amino]-N-(2-cryptomaterial)benzamide (compound 66),

2-[(pyridine-4-ylmethyl)amino]-N-(3-cryptomaterial)benzamide (compound 67),

2-[(pyridine-4-ylmethyl)amino]-N-(4-cryptomaterial)benzamide (compound 68),

N-(2-differentoccasions)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 69),

2-[(pyridine-4-ylmethyl)amino]-N-(2-triftormetilfullerenov)benzamide (compound 70),

N-(6-chlorobenzo[1,3]dioxol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 71),

N-(benzo[1,3]dioxol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 72),

N-(indan-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 73),

N-(3-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 74),

N-(2-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 75),

N-(4-cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 76),

N-(3-bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 77),

N-(2-chloro-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 78),

N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 79),

N-(4-cyano-2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 80),

N-(bromo-5-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 81),

N-(4-cyanonaphthalene-1 ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 82),

N-(4-(morpholine-4-ivasilaki)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 83),

N-(2-morpholine-4-yl-benzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 84),

N-(2-aminobenzoate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 85),

N-(2-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 86),

methyl ester of 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid

(compound 87),

3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 88),

4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 89),

N-[4-(morpholine-4-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 90),

N-{3-[4-(3-cyano-2-yl)piperazine-1-carbonyl]benzyloxy}-2-[(pyridine-4-

ylmethyl)amino]benzamide (compound 91),

N-[3-(4-methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 92),

N-[3-(morpholine-4-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 93),

N-[3-(3-hydroxypyrrolidine-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 94),

N-[4-(4-methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 95),

N-[3-(2-dimethylaminoethyl rebamol)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 96),

N-[3-(2-pyrrolidin-1-iletileri)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 97),

2-[(pyridine-4-ylmethyl)amino]-N-(2-thiophene-2-ivasilaki)benzamide (compound 98),

N-(4'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 99),

N-(naphthalene-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 100),

N-(1-phenylethane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 101),

2-[(pyridine-4-ylmethyl)amino]-N-[1-(2-triptoreline)ethoxy]benzamide (compound 102),

N-(pyridine-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 103),

N-(2,6-dichloropyridine-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 104),

2-[(pyridine-4-ylmethyl)amino]-N-(thiazole-4-ylethoxy)benzamide (compound 105),

N-(2-chlorothiazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 106),

N-(2-phenylthiazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 107),

N-(5-methylisoxazol-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 108),

N-(3,5-dimethylisoxazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 109),

N-(3-propylenoxide-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 110),

N-(5-chlorothiophene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 111),

N-[2-(4-cyanophenyl)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (link is 112),

N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 113),

N-cyclopropylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 114),

N-methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 115),

N-(2,2-DIMETHYLPROPANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 116),

N-(2-ethylbutane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 117),

N-(3-methylbutoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 118),

N-cyclobutylmethyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 119),

N-cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 120),

N-cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 121),

N-cyclooctylmethyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 122),

N-(1-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 123),

N-cyclohexyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 124),

N-(2-cyclopropylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 125),

N-(2-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 126),

N-(3-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 127),

N-(cyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 128),

N-(6-methylcyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 129),

N-(TRANS-4-hydroximate is cyclohexylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 130),

N-(3-methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 131),

N-(adamantane-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 132)

N-(bicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 133),

N-(6,6-dimethylbicyclo[3.1.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 134),

2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-2-ylethoxy)benzamide (compound 135),

2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-3-ylethoxy)benzamide (compound 136),

N-(3-methyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 137),

N-(3-ethyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 138),

N-(3-butyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 139),

2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-yloxy)benzamide (compound 140),

2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-4-ylethoxy)benzamide (compound 141),

2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 142),

4-fluoro-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 143),

2-fluoro-N-(2-methylthiazole-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 144),

5-fluoro-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 15),

3-methoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 146),

N-(4-chlorobenzoyloxy)-3-methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 147),

4,5-dimethoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 148),

N-benzyloxy-4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 149),

2-methyl-N-(2-methylthiazole-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 150),

N-benzyloxy-2-methyl-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 151),

5-methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 152),

N-benzyloxy-5-methyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 153),

5-bromo-N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 154),

N-benzyloxy-5-bromo-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 155),

N-(4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 156),

N-(2-chloro-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide

(compound 157),

N-(4-cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 158),

N-(3-bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 159),

N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 160),

N-(2-bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (with the unity 161),

N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 162),

N-(2-Methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 163),

N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 164),

N-benzyloxy-2-(4-forbindelsen)nicotinamide (compound 165),

N-benzyloxy-2-(4-chlorobenzylamino)nicotinamide (compound 166),

N-benzyloxy-2-(4-methoxybenzylamine)nicotinamide (compound No. 167),

N-benzyloxy-2-(isoquinoline-5-ylamino)nicotinamide (compound 168),

N-(4-cyano-2-methoxybenzyloxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 169),

N-benzyloxy-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 170),

N-(2-methylthiazole-4-ylethoxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 171),

N-benzyloxy-2-(4-forbindelsen)benzamide (compound 172),

N-(4-cyanobenzyl)-2-(4-forbindelsen)benzamide (compound 173),

2-(4-forbindelsen)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 174),

N-Benzyloxy-2-(3-cyano-4-forbindelsen)benzamide (compound 175),

N-(2-bromobenzylamine)-2-(3-cyano-4-forbindelsen)benzamide (compound 176),

methyl ester 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (compound 177),

methyl ester 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid(compound 178),

methyl ester 2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzoic acid (compound 179),

methyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-2-fermenting acid (compound 180),

5-[(2-cyclopentanecarbonitrile)methyl]-2-Formentera acid (compound 181).

2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzoic acid (compound 182),

5-[(2-benzyloxycarbonylamino)methyl]-2-Formentera acid (compound 183),

5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(2-hydroxyethyl)benzamide (compound 184),

5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 185),

5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(4-hydroxybutyl)benzamide (compound 186),

5-[(2-benzyloxycarbonylamino)methyl]-N-(3-dimethylaminopropyl)-2-perbenzoic (compound 187),

5-[(2-cyclopentanecarbonitrile)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 188),

N-cyclopentyloxy-2-[4-fluoro-3-(4-methylpiperazin-1-carbonyl)benzoylamino]benzamide (compound 189),

N-cyclopentyloxy-2-[4-fluoro-3-(morpholine-4-carbonyl)benzoylamino]benzamide (compound 190),

N-benzyloxy-2-(4-methoxybenzylamine)benzamide (compound 191),

2-(4-methoxybenzylamine)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 192),

N-benzyloxy-2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzamide (compound 193),

N-(4-cyanobenzyl)-2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzamide (compound 194),

2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 195),

N-(4-cyanobenzyl)-2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzamide (compound 196),

2-[(benzofuran-5-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 197),

2-[(benzofuran-5-ylmethyl)amino]-N-benzyloxybenzoate (compound 198),

2-[(benzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 199),

N-(4-cyanobenzyl)-2-[(2-oxo-2H-chromen-6-ylmethyl)amino]benzamide (compound 200),

N-(4-chlorobenzoyloxy)-2-(4-cyanobenzylidene)benzamide (compound 201),

2-[(3,5-dichloropyridine-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 202),

N-benzyloxy-2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzamide (compound 203),

2-[(2-bromopyridin-4-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 204),

N-(4-cyano-2-methoxybenzyloxy)-2-[(2-hydroxypyridine-4-ylmethyl)amino]benzamide (compound 205),

2-[(2-aminopyridine-4-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 206),

N-(4-forbindelse)-2-[(2-morpholine-4-yl-pyridine-4-ylmethyl)amino]benzamide (compound 207),

N-cyclopentyloxy-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (link is 208),

N-(4-cyanobenzyl)-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (compound 209),

N-(4-cyanobenzyl)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 210),

N-(4-cyano-2-methoxybenzyloxy)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 211),

N-cyclopentyloxy-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 212),

N-(2,3-debtor-4-methylbenzylamino)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 213),

ethyl ester of [3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 214),

ethyl ester of (3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (compound 215),

[3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 216),

(3-{4-[(2-cyclopentanecarbonitrile) methyl]pyridine-2-yl}ureido)acetic acid (compound 217),

2-[3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)ureido]ethyl ester 2-methylacrylate acid (compound 218),

2-(3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)ethyl ester 2-methylacrylate acid (compound 219),

N-(4-cyanobenzyl)-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}amino)benzamide (compound 220),

N-Cyclops is teletaxi-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}amino)benzamide (compound 221),

(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-ylcarbonyl)methyl ester acetic acid (compound 222),

{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-ylcarbonyl}methyl ether acetic acid (compound 223),

N-(4-cyanobenzyl)-2-{[2-(2-hydroxyacetylamino)pyridine-4-ylmethyl]amino}benzamide (compound 224),

ethyl ester of 4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)carbamino acid (compound 225),

N-(4-cyanobenzyl)-2-{[2-(cyclopropanecarbonyl)pyridine-4-ylmethyl]amino}benzamide (compound 226),

N-cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)pyridine-4-ylmethyl]amino}benzamide (compound 227),

N-cyclopentyloxy-2-({2-[2-(2,5-dioxoimidazolidin-4-yl)acetylamino]pyridine-4-

ylmethyl}amino)benzamide (compound 228),

2-[(2-aminopyridine-4-ylmethyl)amino]-N-Cyclopentasiloxane (compound 229),

N-benzyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 230),

N-(4-cyanobenzyl)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 231),

N-(2-methylthiazole-4-ylethoxy)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 232),

N-cyclopentyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 233),

2-[(quinoline-4-ylmethyl)amino]-N-(tetrahydropyran-4-ylethoxy)benzamide (compound 234),

N-(4-cyano-2-methoxybenzyloxy)-2-[(6-methoxypoly the Jn-3-ylmethyl)amino]benzamide (compound 235),

N-benzyloxy-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 236),

N-(4-cyanobenzyl)-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 237),

N-benzyloxy-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 238),

N-(2,4-dichloraniline)-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 239),

N-(2-methylthiazole-4-ylethoxy)-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 240),

N-benzyloxy-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 241),

N-benzyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 242),

N-cyclopentyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 243),

N-(4-cyanobenzyl)-2-(1-pyridine-4-ylethylamine)benzamide (compound 244),

2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 245),

N-cyclopentyloxy-2-{[2-(2-methoxyethylamine)pyridine-4-ylmethyl]amino}benzamide (compound 246),

N-(4-cyanobenzyl)-2-[(6-oxo-1,6-dihydropyridines-3-ylmethyl)amino]benzamide (compound 247),

N-cyclopentyloxy-2-[(tetrahydropyran-4-ylmethyl)amino]benzamide (compound 248),

N-(3-iodine-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 250),

N-(4-ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 251),

N-(4-isopropylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (connected to the e 252),

N-(4-tert-butylbenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 253),

N-(2-ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 254),

N-(2-non-1-universilence)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 255),

N-(4-phenylenedimethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 256),

N-(4-diethylaminoethylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 257),

N-(2-carbamoylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 258),

N-[4-cyano-2-(2-methoxyethoxy)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 259),

N-(4-cyanomethyl-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 260),

N-(5-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 261),

tert-butyl ester 2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}phenyl)carbamino acid (compound 262),

N-(2-acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 263),

N-(2-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 264),

N-(2-methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 265),

N-(4-acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 266),

N-(biphenyl-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 267),

N-(biphenyl-2-ylethoxy)--[(pyridine-4-ylmethyl)amino]benzamide (compound 268),

N-(3'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 269),

N-(2'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 270),

N-(3'-hydroxymethyluracil-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 271),

N-(3-phenoxybenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 272),

N-(anthracene-9-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 273),

N-[4-(2-methylthiazole-4-yl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 274),

N-(2-methanesulfonamido-1 venlafaxi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 275),

2-[(pyridine-4-ylmethyl)amino]-N-[2-(4-triptoreline)thiazole-4-ylethoxy]benzamide (compound 276),

2-[(pyridine-4-ylmethyl)amino]-N-(3-para-tolerization-5-ylethoxy)benzamide (compound 277),

N-(3-methylisoxazol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 278),

N-(3-utilization-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 279),

N-(3-butylisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 280),

N-(3-penilesecrets-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 281),

2-[(pyridine-4-ylmethyl)amino]-N-[5-(3-triptoreline)-[1,2,4]oxadiazol-3-ylethoxy]benzamide (compound 282),

N-(1-benzyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (Conn is out 283),

N-(1-cyclopentyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 284),

N-(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 285),

N-(3-phenoxypropane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 286),

N-(3-benzyloxypropionic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 287),

N-(2-benzyloxyethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 288),

N-[2-hydroxy-3-(4-methoxyphenoxy)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 289),

N-(3-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 290),

N-(4-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 291),

N-(2-methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 292),

N-(4-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 293),

N-(3-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 294),

N-[2-(4-cyanobenzenesulfonyl)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 295),

N-[3-(4-cyanobenzenesulfonyl)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 296),

N-(3-phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 297),

N-(2-phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 98),

N-[3-(2-acetylamino-4-methylthiazole-5-sulfonylamino)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 299),

N-[2-(2-acetylamino-4-methylthiazole-5-sulfonylamino)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 300),

N-(2-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 301),

N-(4-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 302),

tert-butyl ether (2-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}ethyl) - carbamino acid (compound 303),

tert-butyl methyl ether (3-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}propyl)carbamino acid (compound 304),

tert-butyl ester (4-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}butyl)carbamino acid (compound 305),

N-[2-(3-phenylthioureido)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 306),

N-[4-(3-phenylthioureido)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 307),

N-[2-(3-phenylurea)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 308),

N-[3-(3-phenylurea)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 309),

N-[4-(3-phenylurea)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 310),

N-(2-aminoethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 311),

N-(3-aminopropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 312),

N-(4-aminobutoxy)-2-[(pyridine-4-ylmethyl)AMI is about]benzamide (compound 313),

N-(2-morpholine-4-yl-2-oksidoksi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 314),

N-[(2-methoxyphenylacetyl)methoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 315),

N-tert-butoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 316),

N-isobutoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 317),

N-(2-methylacrylate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 318),

N-(3-methylbut-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 319),

N-(4-hydroxyben-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 320),

N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 321),

N-cyclooctylamino-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 322),

N-(2-cyclohexylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 323),

N-(2-methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 324),

N-(4-methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 325),

N-(4-methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 326),

N-(3-methylbicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 327),

N-(bicyclo[2.2.1]hept-5-ene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 328),

tert-butyl ether benzyl-(2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}cyclohexyl)carbamino acid the (compound 329),

N-(2-benzylaminocyclohexanemethanol)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 330),

N-(3-propyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 331),

N-(3-pentyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 332),

4-methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 333),

N-(5-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 334),

2 benzylamino-N-benzyloxy-nicotinamide (compound 335),

2 benzylamino-N-(4-methoxybenzyloxy)nicotinamide (compound 336),

N-benzyloxy-2-(2-chlorobenzylamino)nicotinamide (compound 337),

2-(2-chlorobenzylamino)-N-(4-methoxybenzyloxy)nicotinamide (compound 338),

N-benzyloxy-2-(2,4-dichloraniline)nicotinamide (compound 339),

2-(3,5-dichloraniline)-N-(4-methoxybenzyloxy)nicotinamide (compound 340),

N-benzyloxy-2-(2-methoxybenzylamine)nicotinamide (compound 341),

2-(2-methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 342),

N-benzyloxy-2-(2-pyridin-4-ylethylamine)nicotinamide (compound 343),

N-(2-bromobenzylamine)-2-([1,2,4]triazole-4-ylamino)nicotinamide (compound 344),

tert-butyl ether 4-{[3-(4-methoxybenzyloxy)pyridine-2-ylamino]methyl}piperidine-1-carboxylic acid (compound 345),

N-benzyloxy-5-[(2-benzo is oxycarbonyl)methyl]-2-perbenzoic (compound 346),

N-(2-bromobenzylamine)-2-(3-cyano-4-methoxybenzylamine)benzamide (compound 347),

N-(2-bromobenzylamine)-2-(4-methanesulfonanilide)benzamide (compound 348),

2-[4-(methoxyaminomethyl)benzylamino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 349),

N-(2-bromobenzylamine)-2-[(2,6-dichloropyridine-4-ylmethyl)amino]benzamide (compound 350),

N-benzyloxy-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 351),

N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 352),

N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 353),

N-benzyloxy-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 354),

N-benzyloxy-2-[(3-bromopyridin-2-ylmethyl)amino]benzamide (compound 355),

2-[(3-bromopyridin-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 356),

N-(2,4-dichloraniline)-2-[(2,6-dimethoxypyrimidine-4-ylmethyl)amino]benzamide (compound 357),

N-benzyloxy-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 358),

N-(2,4-dichlorobenzyl)-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 359),

N-benzyloxy-2-[(1-methyl-1H-imidazol-2-ylmethyl)amino]benzamide (compound 360),

2-[(1-methyl-1H-imidazol-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 361),

N-benzyloxy-2-[(3-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 362),

2-[(3-methyl-3H-they are the azole-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 363),

N-benzyloxy-2-[(5-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 364),

2-[(5-methyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 365),

2-[(2-ethyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 366),

N-benzyloxy-2-[(2-ethyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 367),

N-(2,5-dichloraniline)-2-[(5-oxopyrrolidin-2-ylmethyl)amino]benzamide (compound 368),

N-benzyloxy-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 369),

N-benzyloxy-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 370),

ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 371),

ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 372),

ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 373),

N-(4-cyanobenzyl)-2-[(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 374),

N-(4-cyanobenzyl)-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 375),

N-(4-cyanobenzyl)-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 376),

ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]met the l}-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 377),

ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 378),

ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 379),

N-(4-cyanobenzyl)-2-[(3-methylisoxazol-5-ylmethyl)amino]benzamide (compound 380),

N-(4-cyanobenzyl)-2-[(3-utilization-5-ylmethyl)amino]benzamide (compound 381),

N-(4-cyanobenzyl)-2-[(3-propylenoxide-5-ylmethyl)amino]benzamide (compound 382),

N-(4-cyanobenzyl)-2-[(3,5-dimethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 383),

N-(4-cyanobenzyl)-2-[(3-ethyl-5-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 384),

N-(4-cyanobenzyl)-2-[(5-methyl-3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 385),

N-benzyloxy-2-[(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 386),

N-(4-cyanobenzyl)-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 387),

N-cyclopentyloxy-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 388),

N-(4-cyanobenzyl)-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 389),

N-cyclopentyloxy-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 390),

N-(4-cyanobenzyl)-2-[2-(3-propyl-4-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 391),

N-cyclopentyloxy-2-[2-(3-propyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 392),

N-benzyloxy-2-[2-(2,4-dioxo-imidazolidin-1-yl)ethylamino]benzamide (compound 393),

N-benzyloxy-2-[(6-chloroimidazo[2,1-b]thiazole-5-ylmethyl)amino]benzamide (compound 395),

N-benzyloxy-2-[(2-methylimidazo[1,2-a]pyrimidine-3-ylmethyl)amino]benzamide (compound 396),

N-benzyloxy-2-(2-benzyloxyaniline)benzamide (compound 397),

N-(2-benzyloxycarbonyl)isonicotinamide (compound 398),

N-benzyloxy-2-(2-pyridin-4-yl-acetylamino)benzamide (compound 399),

N-benzyloxy-N-methyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 400),

N-(5-oxopyrrolidin-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 402),

tert-butyl ether 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}piperidine-1-carboxylic acid (compound 403),

N-cyclopentyloxy-2-{[6-(cyclopropanecarbonyl)pyridine-3-ylmethyl]amino}benzamide (compound 404),

N-cyclopentyloxy-2-[(6-pyrrolidin-1-yl-pyridine-3-ylmethyl)amino]benzamide (compound 405),

2-[(6-aminopyridine-3-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 406),

N-(4-cyanobenzyl)-2-[(6-pyrrolidin-1-yl-pyridine-3-ylmethyl)amino]benzamide (compound 407),

N-cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)-4-methylthiazole-5-ylmethyl]amino}benzamide (compound 408),

2-[(6-aminopyridine-3-ylmethyl)amino]-N-Cyclopentasiloxane (compound 409),

N-[3-(2,2-dibromovinyl)cyclopentyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 410),

N-(3-hydroxymethylcellulose)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 411),

N-(2-hydroxyethylacrylate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 412),

N-[4-(4-methylpiperazin-1-ylmethyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 413),

N-{4-[4-(2-hydroxyethyl)piperazine-1-ylmethyl]benzyloxy}-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 414),

N-(4-cyanobenzyl)-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (compound 415),

N-(4-cyanobenzyl)-2-{[2-(3-ethylurea)pyridine-4-ylmethyl]amino}benzamide (compound 416),

N-cyclopentyloxy-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (compound 417),

N-cyclopentyloxy-2-{[2-(3-propylurea)pyridine-4-ylmethyl]amino}benzamide (compound 418),

N-cyclopentyloxy-2-{[2-(3-ethylurea)pyridine-4-ylmethyl]amino}benzamide (compound 419),

N-(3-hydroxycyclopent)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 420),

N-cyclopentyloxy-2-{[2-(3-methylthiourea)pyridine-4-ylmethyl]amino}benzamide (compound 421),

2-{[2-(3-tert-butylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 422),

N-(4-cyanobenzyl)-2-{[2-(3-cyclohexylurea)pyridine-4-ylmethyl]amino}benzamide (compound 23),

2-{[2-(3-cyclohexylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 424),

N-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}isonicotinamide (compound 425),

1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid {4-[(2-

cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide (compound 426),

(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide 1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid (compound 427),

{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide 1-acetylpiperidine-4-carboxylic acid (compound 428),

(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide 1-acetylpiperidine-4-carboxylic acid (compound 429),

N-cyclopentyloxy-2-[(2,4-dihydroxy-pyrimidine-5-ylmethyl)amino]benzamide (compound 430),

(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide, pyrrolidin-2-carboxylic acid (compound 431),

{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide pyrrolidin-2-carboxylic acid (compound 432) and 2-[(pyridine-4-ylmethyl)amino]-N-(4-vinylbenzoate)benzamide (compound 433).

The compounds of formula I can be obtained in crystalline form directly the concentration of the organic solvent or by crystallization or recrystallization from the solvent content of inorganic fillers, or a mixture of the solvent and co-solvent, which can be organic or inorganic, for example water. Crystals can be distinguished in form, essentially solvent free or in the form of MES, such as a hydrate. The invention covers all crystal modifications and forms, and mixtures thereof.

The compounds of formula I may contain asimmetricheskii substituted (chiral) carbon atoms and carbon-carbon double bond, which can exist in isomeric form, such as enantiomers, diastereomers and geometric isomers. The present invention applies to all such isomers in pure form or as mixtures thereof. The invention also concerns all possible tautomers of the compounds of formula I.

Compounds suitable as intermediate products for the synthesis of compounds of formula I, in particular, can be selected from a list including:

O-(3,4,5-trimethoxybenzyl)hydroxylamine (receiving 8),

O-(4-Chlorobenzyl)hydroxylamine (9),

4-aminoacetonitrile (10),

O-quinoline-2-almatygidrogeologiya (11),

O-(2-methylthiazole-4-ylmethyl)hydroxylamine (receiving 12),

O-(4-fluoro-2,6-dimethylbenzyl)hydroxylamine (13),

O-(4-fluoro-2-methoxybenzyl)hydroxylamine (getting 14),

O-(2,3-debtor-4-methylbenzyl)hydroxylamine (getting 15),

O-(3-fluoro-4-methylbenzyl)hydroxylamine (receipt is 16),

O-(5-fluoro-2-methylbenzyl)hydroxylamine (getting 17),

O-(2,3,5,6-titrator-4-methoxybenzyl)hydroxylamine (getting 18),

O-(4-bromobenzyl)hydroxylamine (getting 19),

O-(2-jobensis)hydroxylamine (20),

O-(3-jobensis)hydroxylamine (getting 21),

(2-aminoacetonitrile)acetonitrile (getting 22),

O-(2-benzensulfonamidelor)hydroxylamine (23),

(4-aminoantipyrine)methanol (getting 24),

O-(4-fluoro-2-trifloromethyl)hydroxylamine (getting 25),

O-(2-fluoro-6-trifloromethyl)hydroxylamine (getting 26),

O-(4-fluoro-3-trifloromethyl)hydroxylamine (getting 27),

O-(4-methyl-3-trifloromethyl)hydroxylamine (getting 28),

O-(4-methoxy-3-trifloromethyl)hydroxylamine (getting 29),

O-(2-methoxybenzyl)hydroxylamine (30),

O-(4-interoceanic)hydroxylamine (getting 31),

O-(2-cryptomaterial)hydroxylamine (getting 32),

O-(3-cryptomaterial)hydroxylamine (receiving 33),

O-(4-cryptomaterial)hydroxylamine (getting 34),

O-(2-deformational)hydroxylamine (getting 35),

O-(2-triftormetilfullerenov)hydroxylamine (getting 36),

O-(6-chlorobenzo[1,3]dioxol-5-ylmethyl)hydroxylamine (getting 37),

O-benzo[1,3]dioxol-5-almatygidrogeologiya (received 38),

O-indan-5-almatygidrogeologiya (getting 39),/p>

3-aminoacetonitrile (getting 40),

2-aminoacetonitrile (getting 41),

4-aminoacetyl-3-perbenzoate (getting 42),

4-aminoacetyl-2-bromobenzonitrile (getting 43),

4-aminoacetyl-3-chlorobenzonitrile (getting 44),

4-aminoacetyl-3-methoxybenzonitrile (45),

4-aminoacetyl-3-idententical (getting 46),

3-aminoacetyl-4-bromobenzonitrile (getting 47),

4-aminoacetyl-naphthalene-1-carbonitrile (getting 48),

O-(4-(morpholine-4-ylbenzyl)hydroxylamine (getting 49),

O-(2-morpholine-4-ylbenzyl)hydroxylamine (getting 50),

O-(2-aminobenzyl)hydroxylamine (getting 51),

methyl ether 3-aminooxyacetic acid (getting 52),

O-naphthalene-1-almatygidrogeologiya (receipt of 53)

O-(1-phenylethyl)hydroxylamine (getting 54),

O-[1-(2-triptoreline)ethyl]hydroxylamine (getting 55),

O-pyridine-2-almatygidrogeologiya (receiving 56),

O-(2,6-dichloropyridine-4-ylmethyl)hydroxylamine (getting 57),

O-thiazole-4-almatygidrogeologiya (getting 58),

O-(2-chlorothiazole-5-ylmethyl)hydroxylamine (getting 59),

O-(2-phenylthiazol-4-ylmethyl)hydroxylamine (getting 60),

O-(5-Methylisoxazol-3-ylmethyl)hydroxylamine (getting 61),

O-(3,5-dimethylisoxazol-4-ylmethyl)hydroxylamine (62 receiving),

O-(3-propylenoxide-5-ylmethyl)hydroxylamine (recip is of 63),

O-(5-chlorothiophene-2-ylmethyl)hydroxylamine (getting 64),

4-(2-aminoacetyl)benzonitrile (getting 65),

O-cyclopentanecarboxylate (getting 66),

O-cyclopropylmethoxy (getting 67),

O-(2,2-dimethylpropyl)hydroxylamine (getting 68),

O-(2-ethylbutyl)hydroxylamine (getting 69),

O-isobutylpyrazine (getting 70),

O-cyclobutanedicarboxylate (getting 71),

O-cyclohexylethylamine (receive 72),

O-cycloheptylmethyl (getting 73),

O-cyclooctatetraene (getting 74),

O-(1-cyclopentylmethyl)hydroxylamine (getting 75),

O-cyclohexylhydroxylamine (getting 76),

O-(2-cyclopropylethyl)hydroxylamine (getting 77),

O-(2-cyclopentylmethyl)hydroxylamine (getting 78),

O-(3-cyclopentylpropionyl)hydroxylamine (getting 79),

O-cyclohex-3-animatingdemocracy (80),

O-(6-methylcyclohex-3-animetal)hydroxylamine (getting 81),

(4-aminoacetanilide)methanol (getting 82),

O-(3-methoxycyclohexyl)hydroxylamine (getting 83),

O-adamantane-1-almatygidrogeologiya (getting 84),

O-bicyclo[2.2.1]hept-2-almatygidrogeologiya (getting 85),

O-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethyl)hydroxylamine (getting 86),

O-(tetrahydrofuran-2-ylmethyl)hydroxylamine (getting 87),

O-(tetrahydrofuran-3-yl is ethyl)hydroxylamine (getting 88),

O-(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (getting 89),

O-(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (getting 90),

O-(3-butyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (getting 91),

O-(tetrahydropyran-4-ylmethyl)hydroxylamine (getting 92),

O-(tetrahydropyran-2-ylmethyl)hydroxylamine (getting 93),

O-(3-iodine-4-methylbenzyl)hydroxylamine (getting 94),

O-(4-active compounds)hydroxylamine (getting 95),

O-(4-isopropylbenzyl)hydroxylamine (getting 96),

O-(4-tert-butylbenzyl)hydroxylamine(getting 97),

O-(2-active compounds)hydroxylamine (getting 98),

O-(2-non-1-universal)hydroxylamine (getting 99),

O-(4-phenylenedimethylene)hydroxylamine (100),

O-(4-diethylaminomethyl)hydroxylamine (getting 101),

2-(2-aminoacetonitrile)ndimethylacetamide (getting 102),

4-aminoacetyl-3-(2-methoxyethoxy)benzonitrile (getting 103),

(4-aminoacetyl-3-methoxyphenyl)acetonitrile (getting 104),

3-aminoacetyl-4-methoxybenzonitrile (getting 105),

tert-butyl ether (2-aminoacetonitrile)carbamino acid (106),

N-(2-aminoacetonitrile)ndimethylacetamide (getting 107),

N-(2-aminoacetonitrile)benzamide (getting 108),

N-(2-aminoacetonitrile)methanesulfonamide (getting 109),

N-(2-aminoacetonitrile)ndimethylacetamide (getting 110),

O-biphenyl-4-yl is ethylhydroxylamine (getting 111),

O-biphenyl-2-almatygidrogeologiya (getting 112),

O-(3'-methoxybiphenyl-2-ylmethyl)hydroxylamine (getting 113),

O-(2'-methoxybiphenyl-2-ylmethyl)hydroxylamine (getting 114),

(2'-aminoacetanilide-3-yl)methanol (getting 115),

O-(3-phenoxybenzyl)hydroxylamine (getting 116),

O-anthracene-9-almatygidrogeologiya (getting 117),

O-[4-(2-methylthiazole-4-yl)benzyl]hydroxylamine (getting 118),

N-(2-aminooxy-2-phenylethyl)methanesulfonamide (getting 119),

O-[2-(4-triptoreline)thiazole-4-ylmethyl]hydroxylamine (getting 120),

O-(3-para-tolerization-5-ylmethyl)hydroxylamine (getting 121),

O-(3-methylisoxazol-5-ylmethyl)hydroxylamine (getting 122),

O-(3-utilization-5-ylmethyl)hydroxylamine (getting 123),

O-(3-butylisoxazole-5-ylmethyl)hydroxylamine (getting 124),

O-(3-penilesecrets-5-ylmethyl)hydroxylamine (getting 125),

0-[5-(3-triptoreline)-[1,2,4]oxadiazol-3-ylmethyl]hydroxylamine (getting 126),

O-(1-benzyl-1H-[1,2,3]triazole-4-ylmethyl)hydroxylamine (getting 127),

O-(1-cyclopentyl-1H-[1,2,3]triazole-4-ylmethyl)hydroxylamine (getting 128),

5-aminoacetyl-2,4-dihydro-[1,2,4]triazole-3-one (getting 129),

O-(3-phenoxypropan)hydroxylamine (getting 130),

O-(3-benzyloxyphenyl)hydroxylamine (getting 131),

O-(2-benzyloxyethyl)hydroxylamine (getting 132),

N-(3-aminocaproyl)benzamide(getting 133),

N-(4-aminoacetyl)benzamide (getting 134),

N-(2-aminoacetyl)methanesulfonamide (getting 135),

N-(4-aminoacetyl)benzosulfimide (getting 136),

N-(3-aminocaproyl)benzosulfimide (getting 137),

N-(2-aminoacetyl)-4-cyanobenzenesulfonyl (getting 138),

N-(3-aminocaproyl)-4-cyanobenzenesulfonyl (getting 139),

N-(3-aminocaproyl)-C-phenylmethanesulfonyl (getting 140),

N-(2-aminoacetyl)-C-phenylmethanesulfonyl (getting 141),

N-[5-(3-aminoacidopathies)-4-methylthiazole-2-yl]ndimethylacetamide (getting 142),

N-[5-(2-aminoacetaldehyde)-4-methyl-thiazol-2-yl]ndimethylacetamide (getting 143),

O-(2-benzylamino)hydroxylamine (receive 144),

O-(4-benzylaminopurine)hydroxylamine (getting 145),

tert-butyl ether (2-aminoacetyl)carbamino acid (getting 146),

tert-butyl methyl ether (3-aminocaproyl)carbamino acid (getting 147),

tert-butyl ester (4-aminoacetyl)carbamino acid (getting 148),

O-isobutylpyrazine (getting 149),

O-(2-methylallyl)hydroxylamine (getting 150),

5-aminooctane-3-EN-2-ol (getting 151),

O-cyclopentanecarboxylate (getting 152),

O-cyclooctatetraene (getting 153),

O-(2-cyclohexylethyl)hydroxylamine (getting 154),

O-(2-methylcyclohexylamine)hydroxylamine (getting 155),

O-(4-methyl shall illogicality)hydroxylamine (getting 156),

O-(4-methoxycyclohexyl)hydroxylamine (getting 157),

O-(3-methylbicyclo[2.2.1]hept-2-ylmethyl)hydroxylamine (getting 158),

O-bicyclo[2.2.1]hept-5-ene-2-almatygidrogeologiya (getting 159),

tert-butyl ether (2-aminoheterocycles)benzylcarbamoyl acid (getting 160),

O-(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (getting 161),

O-(3-pentyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (getting 162),

5-aminoacetyl-pyrrolidin-2-it (getting 163),

tert-butyl ether 4-aminoacetanilide-1-carboxylic acid (getting 164),

O-[3-(2,2-dibromovinyl)cyclopentylmethyl]hydroxylamine (getting 165),

(3-aminoacetanilide)methanol (getting 166),

(2-aminoheterocycles)methanol (getting 167),

O-[4-(4-methylpiperazin-1-ylmethyl)benzyl]hydroxylamine (getting 168),

2-[4-(4-aminoantipyrine)piperazine-1-yl]ethanol (getting 169) and 3-aminoacetophenone (getting 170); and their salts with hydrochloric acid, Hydrobromic acid or sulfuric acid.

Still other compounds suitable as intermediate products for the synthesis of compounds of formula I may, in particular, be selected from the list including:

4-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid (receiving 1A),

2-fluoro-6-[(pyridine-4-ylmethyl)amino]benzoic acid (receive (B)

5-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid (receiving 1C),

3-Methoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (receiving 1D),

4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 1E),

2-methyl-6-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 1F),

5-methyl-2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 1G),

5-bromo-2-[(pyridine-4-ylmethyl)amino]benzoic acid (receiving 1H),

3-[(pyridine-4-ylmethyl)amino]isonicotinoyl acid (getting 1I),

2-(4-forbindelsen)benzoic acid (getting 1J),

2-(3-cyano-4-forbindelsen)benzoic acid (getting 1K),

methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid (obtaining 1L),

2-(4-methoxybenzylamine)benzoic acid (getting 1M),

2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzoic acid (getting 1N),

2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzoic acid (10),

2-[(benzofuran-5-ylmethyl)amino]benzoic acid (IP),

2-[(2-oxo-2H-chromen-6-ylmethyl)amino]benzoic acid (getting 1Q),

2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzoic acid (getting 1R),

2-[(2-bromopyridin-4-ylmethyl)amino]benzoic acid (getting 1S),

2-[(2-hydroxypyridine-4-ylmethyl)amino]benzoic acid (getting 1T),

2-[(2-morpholine-4-yl-pyridine-4-ylmethyl)amino]benzoic acid (auchenia 1U),

2-[(quinoline-4-ylmethyl)amino]benzoic acid (getting 1V),

2-[(6-methoxypyridine-3-ylmethyl)amino]benzoic acid (receiving 1W),

2-[(thiazol-5-ylmethyl)amino]benzoic acid (getting 1X),

2-[(tetrahydropyran-4-ylmethyl)amino]benzoic acid (getting 1Y),

2-[(pyridine-4-ylmethyl)amino]nicotinic acid (getting 2),

2-(4-forbindelsen)nicotinic acid (3),

2-(4-chlorobenzylamino)nicotinic acid (receiving 3A),

2-(isoquinoline-5-ylamino)nicotinic acid (receiving 3B),

2-(4-methoxybenzylamine)nicotinic acid (getting 4),

2-[(pyridine-4-ylmethylamino]nicotinamide (getting 5),

2-(4-forbindelsen)nicotinamide (obtaining 6),

2-(4-methoxybenzylamine)nicotinamide (receiving 7),

2-(isoquinoline-5-ylamino)nicotinamide (receiving 3B),

1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (receiving 7A),

1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (getting 7B),

pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C),

4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)benzonitrile (receiving 7D),

l-(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (getting 7E),

1-(2-imidazol-1-retil)-1H-benzo[d][1,3]oxazin-2,4-dione (getting 7F),

1-(1-pyridine-4-retil)-1H-benzo[d][1,3]oxazin-2,4-dione (getting 7G),

1-(6-oxo-,6-dihydropyridines-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (getting 7H), and

1-(6-oxo-1,6-dihydropyridines-3-ylmethyl)-1H-pyrido[2,3-d][1,3]oxazin-2,4-dione (getting 7I).

The formation of new blood vessels occurs when the balance of factors working for and against this formation, that is, when the balance between Pro-angiogenic and anti-angiogenic compounds. At the beginning of the development of proliferating and differentiating endothelial cells form the blood vessels in the previously avascular tissue. This first stage is movable grid, which is transformed, reaching formed vessel. This process is known as vasculogenesis. The formation of new blood vessel can also occur from an existing blood vessel in a process called angiogenic sprouting. Here the "old" first vessel is destabilized in a particular place, and is formed from it, and then build a new vessel.

The above method typically includes the vascular endothelium, which is a special type of endothelium, consisting of a single layer of smooth cells, which cover the lumen of blood vessels. Identified a number of specific growth factors acting on the specified endothelium, and they include five members of the family of vascular endothelial growth factors (VEGF), four member of the angiopoietin family and one member of a large family afrina. However, VEGF is p is the position of the most crucial generator of education vessels, as it is necessary for the early formation of immature vessels by vasculogenesis and angiogenic sprouting [Yancopoulos, Nature, 407, 242-248, 2000]. VEGF, originally called "vascular permeability factor" (VPF), is an angiogenic factor that is in the center of the network regulating the growth and differentiation of the vascular system and its components during embryonic development, normal growth and with a large number of pathological anomalies along with cellular receptors [G. Breier and others, Trends in Cell Biology 6, 454-6, 1996].

VEGF is a dimeric, disulfide-linked 46 kDa glycoprotein related to the "growth factors derived from platelets" (PDGF); it is produced by normal cell lines and tumor cell lines; it is a mitogen specific regarding endothelial cells; shows angiogenic activity inin vivoresearch systems (for example, in the rabbit cornea), is chemotactic for endothelial cells and monocytes and induces plasminogen activators in endothelial cells, which are included in the proteolytic degradation of extracellular matrix during the formation of capillaries. Known for a number of isoforms of VEGF, demonstrating comparable biological activity, but differ in the type of cells that distinguish them, and their ability to bind GE is ARIN. In addition, there are other members of the VEGF family, such as growth factor, placenta" (PIGF and VEGF-C.

VEGF is unique in that they are the only angiogenic growth factors, which are known to contribute to hyperproliferate vessels and the formation of edema. Indeed, hyperfrontality vessels and swelling that is associated with the expression or introduction of many other growth factors, apparently mediated VEGF production. Inflammatory cytokines stimulate the production of VEGF. As a result of hypoxia markedly positive regulation of VEGF in many tissues, so the situation, including heart attack, thrombosis, ischemia, anemia or poor circulation, typically called VEGF/VPF-mediated reactions. As a result of hyperprolinemia vascular-associated edema, altered transendothelial metabolism and macromolecular extravasation, which is often accompanied by diapedesis may occur excessive deposition of matrix, aberrant proliferation of stroma, fibrosis, etc. Therefore, VEGF-mediated hyperproliferate can significantly contribute to violations of data etiological characteristics. Essentially, the regulators of angiogenesis have become important therapeutic agents.

There are three known VEGF receptors: VEGFR-1 (or receptor fms-like tyrosine kinase (Flt-1)), VEGFR-2 and VEGFR-3, and their expression made tsetse almost exclusively on endothelial cells. VEGFR-2 was designated previously as KDR (receptor containing the domain with the kinase insert), and, apparently, this receptor plays a key role in the induction of cell proliferation by VEGF [Ellis, Seminars in Oncology, 28, 94-104, 2001]. VEGF-receptors belong to the group tyrosinekinase receptors and consist of seven extracellular Ig-like domains hiding place VEGF-binding, and intracellular tyrosinekinase domain. Intra - and extracellular domains are linked short transmembrane segment [Shawver, DDT, 2, 50-63, 1997]. Like other receptors tyrosinekinase VEGFR-2 timeresults after binding to VEGF, and tyrosinekinase domain becomes autophosphorylated. This activated form, in turn, binds to other molecules, which are activated, for example, through another phosphorylation. This cascade ultimately triggers the proliferation of endothelial cells and, thus, the formation of new blood vessels.

Tumor cells require oxygen for growth and metastasis. Oxygen has a very limited range of diffusion, therefore, tumor growth is very limited size, they cannot rely on passive transport of oxygen, but rather set the active transport of oxygen, that is, they should involve the blood vessels of the media. Nourishing washes the VA, required for tumor, are also served through the blood vessels. The tumor is formed in the avascular area or, ultimately, it is distributed, resulting in low values of pO2and pH, and these factors initiate positive regulation of, for example, VEGF in tumor cells. Without a sufficient supply of oxygen and nutrients tumor cells undergo necrosis or apoptosis and tumor stops growing and may even decrease. Angiogenesis is an unconditional prerequisite for tumors that grow over a diameter of approximately 1-2 mm; up to this size, oxygen and nutrients can be delivered to tumor cells via diffusion. Thus, the growth of each tumor, regardless of its nature and causes after reaching a certain size depends on angiogenesis. A large number of tumors in people, especially gliomas and carcinomas, Express high levels of VEGF. This led to the hypothesis that VEGF produced by tumor cells, stimulates the growth of blood capillaries and proliferation of tumor endothelial paracrine manner and through improved blood flow accelerates tumor growth. Increased expression of VEGF may explain the presence of cerebral edema in patients with glioma. Direct evidence of the role of VEGF as a factor in tumor angiogenesisin vivop is shown in studies where inhibit the expression of VEGF or VEGF activity. This is done by using anti-VEGF antibodies, dominant-negative mutant VEGFR-2, which inhibit the signal transduction, and methods using antisense VEGF RNA. All approaches lead to the reduction ofin vivogrowth of cell lines of gliomas or other tumor cell lines in the inhibited tumor angiogenesis. Already in 1971, Folkman hypothesized that inhibition of angiogenesis may be a strategy for the treatment of cancer, which appear solid tumors [Folkman, in Cancer Medicine, (Eds Holland, and others), 132-152, Decker Ontario, Canada, 2000]. This view is based on earlier observations that angiogenesis occurs around tumors, and on the hypothesis that tumors produce "angiogenic factor.

Three fundamental mechanism play an important role in the activity of angiogenesis inhibitors against tumors: 1) inhibition of the growth of vessels, especially capillaries, vascular calm tumor, resulting in no growth of the tumor due to the balance achieved between apoptosis and proliferation; 2) prevention of the migration of tumor cells due to the absence of blood flow in the tumor and from it; and 3) inhibition of endothelial cell proliferation, avoiding, thus, paracrine growth stimulating effect on the surrounding tissue caused by the CSOs endothelial cells, which usually cover the vessels [R. Connell and others, Exp. Opin. Ther. Patents, 11, 77-114, 2001]. As mentioned above, the compounds of the present invention inhibit VEGFR-2 (KDR) and thus prevent angiogenesis, i.e. the formation of new blood vessels, and thus, they halted tumor growth and may even reduce it.

Compounds of the invention should be suitable for the prevention, cure or relief of a disease or condition associated with deregulated angiogenesis, such as prevention, treatment or facilitate tumor or neoplastic diseases, including cancer and metastasis, including, but not limited to carcinoma such as bladder cancer, urinary tract, mammary gland, intestine, colon, kidney, liver, small cell or non-small cell carcinoma of the lung, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, head, brain, neck, uterus and skin (including squamous cell carcinoma); hematopoietic tumors of lymphoid origin (including leukemia, acute limfotsity leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, lymphoma Hodgkin's disease, non-Hodgkins lymphoma, lymphoma hairy cell and Burkitt's lymphoma); hematopoietic tumors of myeloid of origin : Guangdong China who deposits (including acute and chronic myelogenous leukemia, myelodysplastic syndrome and promyeloid leukemia); tumors of mesenchymal origin (including fibrosarcoma and rhabdomyosarcoma, and other sarcomas, e.g. soft tissue and bone); tumors of the Central and peripheral nervous system (including astrocytoma, neuroblastoma, glioma and swannery); and other tumors (including melanoma, seminoma, teratocarcinoma, osteosarcoma, pigmentosa xeroderma, keratocanthoma, follicular thyroid cancer and Kaposi's sarcoma).

Preferably the compounds may be suitable for the treatment of neoplasia selected from lung cancer, colon cancer, kidney cancer and breast cancer.

Blood vessels are also of great importance, if there is metastasis of tumors, since metastases are carried in the blood stream. Reduced number of blood vessels in the tumor or around it reduces the metastatic potential of the tumor. Thus, the invention also relates to a method of reducing the metastatic potential of the tumor.

Very small tumors can survive even in the absence of an appropriate system of vessels, and such tumors can begin to grow and to induce angiogenesis when to stop antiangiogenic treatment. So, I think that the treatment of the compounds of the present invention can usefully include the introduction of joint or to Binational therapy with other therapeutically active compounds, commonly used in the treatment of tumors or cancers, such as chemotherapeutic agents, cytotoxic agents, and anticancer agents. Other therapeutically active compounds include inhibitors of protein kinases, such as tyrosine kinase, useful in the treatment of tumors or cancer. Other therapeutically active compounds can be entered together or sequentially, and the decision on the regimen that best meets the needs of the patient, is within the abilities of a qualified physician or veterinarian. Therapeutic agents can also be given in the form of a single composition, for example, separate capsules or tablets having a fixed ratio of active agents. The invention is not limited to the sequence of administration; compounds of the invention can be entered before, simultaneously with or after the introduction of well-known chemotherapy, cytotoxic or anti-cancer agent. Therapeutically active compounds usually used in the treatment of tumors or cancers include derivatives of S-triazine, for example altretamin; enzymes, for example asparaginase; antibiotics such as bleomycin, dactinomycin, daunorubicin, doxorubicin, idarubitsin, mitomycin, epirubicin and plicamycin; alkylating agents, for example busulfan, carboplatin, carmustin, chlorambucil is, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, lomustin, mechlorethamine, melphalan, procarbazine and thiotepa; antimetabolites, such as cladribine, cytarabine, floxuridine, fludarabine, fluorouracil, hydroxyurea, mercaptopurine, methotrexate, gemcitabine, pentostatin and tioguanin; antimitoticescoe agents, such as etoposide, paclitaxel, teniposide, vinblastine, vinorelbine and vincristine; hormonal agents such as aromatase inhibitors, such as aminoglutetimid, corticosteroids, such as dexamethasone and prednisone, and hormone releasing luteiniziruuchi hormone (LH-RH); antiestrogens such as tamoxifen, formestane and letrozole; antiandrogens, for example, flutamide; biological response modifiers, such as lymphokines, such as aldesleukin and other interleukins; an interferon such as interferon-α; growth factors such as erythropoietin, filgrastim and sargramostim; differentiating agents such as derivatives of vitamin D and all-TRANS retinoic acid; immunoregulatory, such as levamisole; and monoclonal antibodies, tumor necrosis factor α and inhibitors of angiogenesis. In conclusion, the treatment of tumors often use ionizing radiation (radiation therapy), hardly defined as a connection, and it can be combined with the compounds of the present invention. Due to severe adverse is known, often experienced by patients receiving anticancer treatment, it is often desirable to introduce therapeutic agents, which themselves do not cure the tumor, but rather help to relieve side effects. Such compounds include amifostine, leucovorin and mesna.

Abnormal or unregulated angiogenesis is associated not only with tumors, but is also involved in a number of other pathological conditions or diseases (see the work of P. Carmeliet & R.K. Jain, Nature, Vol. 407, 2000, pp. 249-257; A.H. Vagnucci & W.W. Li, The Lancet, Vol. 361, 2003, 605-608; B. Xuan, etc., J. Ocular Pharmacology & Therapeutics, Vol. 15(2), 1999, pp. 143-152)associated with the unregulated angiogenesis. Compounds of the present invention would be suitable to prevent, treat, cure, or relief of a disease or condition associated or related to unregulated angiogenesis, but is not limited to this. These conditions or diseases include conditions or diseases characterized by abnormal angiogenesis or vascular dysfunction, acne rosacea, atherosclerosis, hemangioma, hemangioendothelioma, warts, pyogenic granulomas, hair growth, keloid scars, allergic edema, dysfunctional uterine bleeding, follicular cysts, ovarian hyperstimulation, endometriosis, obesity, arthritis, rheumatoid arthritis, synovitis, bone destruction and cartilage, osteomyelitis, the growth of pannus formation osteofit, inflammatory and infectious diseases (hepatitis, pneumonia, glomerulonephritis, asthma, nasal polyps, transplantation, liver regeneration, retinopathy, diabetic retinopathy, neovascular glaucoma, endometriosis, psoriasis, lymphoproliferative disorders, thyroiditis, thyroid cancer, obstructive pulmonary disease or reperfusion injury in cerebral ischemia, Alzheimer's disease and eye diseases, such as acute macular degeneration, age-related macular degeneration, choroidal revascularization (neovascularization), retinitis, CMV retinitis, macular edema and ischemic retinopathy.

In addition, the compounds of the present invention is suitable for treatment of humans, they can also be suitable for use in veterinary medicine for the treatment of animals such as horses, cattle, sheep, pigs, dogs and cats.

For use in therapy, the compounds of the present invention are typically in the form of a pharmaceutical composition or a pharmaceutical preparation. Thus, the invention concerns pharmaceutical compositions containing a compound of formula I, optionally together with one or more other therapeutically active compounds, such as chemotherapeutic agents, anticancer agents, cytotoxic the mini-agents together with a pharmaceutically acceptable excipient or carrier. Examples of such other therapeutically active compounds include compounds commonly used in the treatment of tumors or cancers listed above. The excipient must be "acceptable" in the sense of compatibility with other ingredients of the composition and non-hazardous to its recipient.

If the treatment involves the introduction of another therapeutically active compounds, it is recommended to consult the works of Goodman & Gilman''s The Pharmacological Basis of Therapeutics, 9th Ed., J.G. Hardman and Limbird LE (Eds.), McGraw-Hill 1995, regarding applicable dosages of these compounds.

Conveniently, if the active ingredient contains 0.1 to about 99.9 wt.% song.

The term "unit dose" means a single, that is, a single dose, which you can enter the patient and which can be easily handled and packing, remaining physically and chemically stable unit dose contains the active substance itself or its mixture with a solid or liquid pharmaceutical diluents or carriers. In the form of unit doses of a compound, you can enter one or more times a day with suitable intervals, but always depending on the patient's condition and in accordance with the doctor's prescription. It is also expected that under certain treatment regimens can be a useful introduction large is intervalli, for example, daily, weekly, or even with large intervals.

Conveniently, if the unit dosage contains from 0.01 mg to 10000 mg, preferably from 100 mg to 3000 mg, for example from 200 mg to 1000 mg of the compounds of formula I. Drugs include, for example, drugs in the form of a form suitable for oral administration (including preparations of prolonged or delayed action), rectal, parenteral (including subcutaneous, intraperitoneal, intramuscular, intra-articular and intravenous), transdermal, ocular, local (nasal or transbukkalno introduction.

Drugs can be conveniently presented in the form of single doses and can be prepared by any of the methods well known in the field of pharmacy, for example, as disclosed in the work of Remington, The Science and Practice of Pharmacy, 20th ed., 2000. All methods include the stage of combining the active ingredient with the carrier which constitutes one or more accessory ingredients. Generally, prepare drugs, uniformly and thoroughly mixing the active ingredient with a liquid carrier or a finely ground solid carrier, or both and then, if necessary, shaping the product in the form of the desired drug.

The preparations of the present invention suitable for oral administration may be in the form of discrete units such as capsules, sachets, tablets or pellets, each of Kotor is x contains a predetermined amount of the active ingredient; in the form of a powder or granules; as solution or suspension in an aqueous liquid or non-aqueous liquid, such as ethanol or glycerol; or in the form of an emulsion of the "oil-in-water or emulsion water in oil. Such oils can be a good food oils, such as cottonseed oil, sesame oil, coconut oil or peanut oil. Suitable for the aqueous suspensions or dispersing suspendresume agents include synthetic or natural resins, such as tragakant, alginate, gum Arabic, dextran, sodium carboxymethyl cellulose, gelatin, methylcellulose, hypromellose, hydroxypropylcellulose, carbomer and polyvinylpyrrolidone. The active ingredients can also be introduced in the form of bolus, electuary or paste.

The tablet can be obtained by molding or forming of the active ingredient, optionally with one or more accessory ingredients. Molded tablets can be obtained by pressing on a suitable machine the active ingredient (ingredient) freely in its current form, for example in the form of powder or granules, optionally mixed with a binder, such as, for example lactose, glucose, starch, gelatin, Arabic gum, tragacantha resin, sodium alginate, carboxymethylcellulose, methylcellulose, hypromellose, polyethylene glycol, waxes or under the service; a lubricant, such as, for example, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride or the like; a leavening agent, such as, for example, starch, methylcellulose, agar, bentonite, croscarmelose, matrikamantra, crosspovidone or similar, or dispersing agent such as Polysorbate 80. Molded tablets can be obtained by molding in a suitable machine a mixture of the powdered active ingredient and a suitable carrier, moistened with an inert liquid diluent.

Preparations for rectal injection can be in the form of suppositories in which the compound of the present invention is mixed with low-melting water-soluble or insoluble solids such as cocoa butter, hydrogenated vegetable oil, polyethylene glycol or ethers of fatty acids and glycols, while elixirs can be prepared using ministervalletta.

Preparations suitable for parenteral administration conveniently contain sterile oil or water in the form of active ingredients, which are preferably isotonic with the blood of the recipient, such as isotonic saline, isotonic glucose solution or buffer solution. These drugs can be conveniently sterilized, for example by filtering through a filter that retains bacteria,adding to the drug sterilizing agent, irradiating the drug or by heating the drug. Suitable for parenteral administration are also liposomal preparations are disclosed, for example, in Encyclopedia of Pharmaceutical Technology, vol. 9, 1994.

Alternatively, the compound of the formula I can be represented in the form of sterile solid preparation, such as freeze dried powder, which easily dissolves in sterile solvent immediately prior to use.

Transdermal preparations can be in the form of strips or bandages.

Drugs suitable for ocular administration, can be in the form of a sterile aqueous preparation of the active ingredients, which may be in microcrystalline form, for example in the form of an aqueous microcrystalline suspension. For ocular injection of the active ingredient can also be used liposomal drugs or biorstwami polymer systems which are disclosed, for example, in Encyclopedia of Pharmaceutical Technology, vol.2, 1989.

Drugs that are suitable for local or ocular injection, include liquid or semi-liquid form, such as liquid ointments, lotions, gels, applicators, emulsion oil-in-water" or "water in oil", such as creams, ointments or pastes; or solutions or suspensive, for example, drops.

Drugs suitable for nasal or buccal injection include powders, self-propelled and spray f is RMI, such as aerosols and sprays. These drugs are more disclosed, for example, in Modern Pharmaceutics. 2nd ed., G.S. Banker and C.T. Rhodes (Eds.), page 427-432, Marcel Dekker, New York; Modern Pharmaceutics, 3th ed., G.S. Banker and C.T. Rhodes (Eds.), page 618-619 and 718-721, Marcel Dekker, New York and Encyclopedia of Pharmaceutical Technology, vol. 10. J Swarbrick and J.C. Boylan (Eds), page 191-221, Marcel Dekker, New York.

In addition to the above-mentioned ingredients, the preparations of compounds of formula I can contain one or more ingredients such as diluents, buffers, flavoring agents, dyes, surfactants, thickeners, preservatives, such as methylhydroxybenzoate (including anti-oxidants), emulsifying agents and the like.

If the active ingredient is administered in the form of salts with pharmaceutically acceptable non-toxic acids or bases, the preferred salts are, for example, easily soluble in water or slightly soluble salts to obtain specific and appropriate speed of absorption.

WAYS to GET

Compounds of the present invention can be obtained in a number of ways, well known to experts in the field of organic synthesis. Compounds of the present invention can be synthesized using the methods described below, together with methods known in the field of synthetic organic chemistry, or variations thereof which are known specialist in this field. Preferred methods include, but are not limited to what this means, described below.

The new compounds of formula (I) can be obtained by using the reactions and techniques described in this section. Interaction is carried out in solvents suitable for use reagents and materials and suitable for the ongoing transformations. Also in the synthetic methods described below, we mean that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and the methods of processing, chosen so that they were standard for this interaction, which can be easily understood by the person skilled in the art. Specialist in the field of organic synthesis it is clear that the functional group is present in various parts of the original molecule, the interaction must be compatible with the proposed reagents and interactions. Not all compounds of formula (I)falling under this class may be compatible with certain conditions of the reactions required in some of the above methods. The person skilled in the art will easily understand such restrictions to the substituents that are compatible with the conditions of the reactions, and may use alternative methods.

The compounds of formula (I) can be obtained using techniques and methods that are easily accessible to the person skilled in the art, for example techniques indicated the data in the following diagrams. These schemes are in no way intended to limit the scope of the invention. All substituents, unless otherwise specified, pre-determined. The reagents and starting materials are easily accessible to specialists in this field.

The compounds of formula (I) are generally obtained by condensation of the acids of General formula (II) and O-substituted (Y-A-R9) hydroxylamino General formula (III) under the action of agent combinations, such as a peptide agent combination, optionally in the presence of a base in a suitable solvent, as shown in figure 1. Preferred agents of the combination include N,N'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPP-CI), benzothiazolinone-triprolidine hexaflurophosphate (PyBOP), benzotriazol-1 yloxy-Tris(dimethylamino)phosphonium hexaflurophosphate (BOP), N,N'-dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI). Preferred bases include diisopropylethylamine, triethylamine, 4-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or pyridine or a substituted pyridine, for example, 4-dimethylaminopyridine or 2,6-dimethylpyridin. Preferred solvents are polar aprotic solvents such as dichloromethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone or dimethylformamide. The reaction is usually carried out at a temperature from about -78°C to 60°C and is usually completed the try about a period from about 2 hours to 5 days. The obtained esters, hydroxamic acids of the General structure (I) can be distinguished by extraction with a suitable organic solvent, preferably a solvent that is not miscible with water such as ethyl acetate, after diluting the reaction mixture with water. Evaporation of the solvent under reduced pressure gives products which can additionally be cleaned, if required, by standard methods such as chromatography, crystallization or distillation. Alternative products can be distinguished by removing used for an interaction of the solvent, e.g. by evaporation under reduced pressure, and additionally clear, as mentioned above.

Scheme 1: General method of obtaining benzamido General formula (I) of the acids of General formula (II)

Disclosed compounds typically can also be obtained, as shown in figure 2, the interaction of O-substituted (Y-A-R9) hydroxylamino General formula (III) with "activated" by the acids of General formula IV, where LG denotes a leaving group. Compounds of General structure IV include, but are not limited to this, galodamadruga acids, anhydrides, mixed anhydrides or activated esters such as pentafluorophenyl esters, nitrophenolate ethers or thioethers. The interaction is preferably carried out in the presence of a base, is such as diisopropylethylamine, the triethylamine, 4-methylmorpholine, pyridine or substituted pyridine, for example, 4-dimethylaminopyridine or 2,6-dimethylpyridin. Preferred solvents include polar aprotic solvents such as dichloromethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone or dimethylformamide. The synthesis of esters, hydroxamic acids derived from pentafluorophenyl esters of benzoic acid described previously in WO 02/06213.

Scheme 2: General method of obtaining benzamido General formula (I) of the "activated" acid of General formula (IV).

In addition, the disclosed compounds can usually be obtained, as shown in figure 2a, the interaction of O-substituted (Y-A-R9) hydroxylamino General formula (III) with anhydrides of General formula (XV). The interaction is usually carried out in solvents such as dichloromethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone, dimethylformamide or pyridine. As a rule, spend interaction at a temperature of from about 20°C to 100°C and is usually completed over a period from about 2 hours to 5 days. The obtained esters, hydroxamic acids of the General structure (I) can be distinguished by extraction with a suitable organic solvent, preferably a solvent that is not miscible with water such as ethyl acetate, after diluting the reaction mixture with water. Evaporation of the solvent under reduced pressure gives roducti, which can additionally be cleaned, if required, by standard methods such as chromatography, crystallization or distillation. Alternative products can be distinguished, used for removing the reaction solvent, for example, by evaporation under reduced pressure, and additionally clear, as stated above.

Diagram 2a: General method of obtaining benzamido General formula (I) of the anhydrides of the General formula (XV).

Nitrogen-substituted anhydrides of General formula XV can be obtained from anhydrides of the General formula XI, as shown in figure 2b, by processing anhydrides of General formula XIII alcohols (LG-X-B-R8, LG=OH) by reaction similar to the reaction of Mitsunobu (Mitsunobu), such as the interaction with triphenylphosphine and diethylazodicarboxylate (DEAD) or diisopropylcarbodiimide in a suitable solvent, without limitation, but, for example, tetrahydrofuran or diethyl ether. Alternative N-alkylated anhydrides of General formula XV can be obtained by processing XIIII a suitable base, such as sodium carbonate or sodium hydride, followed by alkylation with a suitable alkylhalogenide (LG-X-B-R8, LG=Cl, Br, I). Non-limiting examples of such receipts is described, for example, in the work of G.M. Coppola: Synthetic Communications (2002), 32, 1009-1013 and the links in it and in WO 00/27819.

Anhydrides of General formula IV are either commercially available, or they can easily be obtained using methods well known to specialists in this field. Non-limiting examples of such receipts described in the work of G.M. Coppola: Synthesis (1980), 505-536; S. Jonsson and others: J. Med. Chem. (2004), 47, 2075-2088; J. Clews, etc.: Tetrahedron (2000), 56, 8735-8746 and U.S. patent 3887550.

Scheme 2b: General method of obtaining substituted on the nitrogen anhydrides of General formula XV anhydrides of the General formula XIIII.

Educt O-substituted (Y-A-R9) hydroxylamine General formula (III) are either commercially available or easily obtained, using techniques well known to the person skilled in the art. Non-limiting examples of such receipts is described, for example, in the work of J.N. Kim and others: Synthetic Communications, (1992) 22, 1427-1432; M. Arimoto, etc.: The Journal of Antibiotics (1988) XLI, 12, 1795-1811, H.M.; Petrassi, etc.: Organic Letters (2001), 3, 139-142; E. Grochowski, and J. Jurczak: Synthesis (1976), 682-684 and WO 02/06213. Typical, but non-limiting synthetic methods for obtaining O-substituted (Y-A-R9) hydroxylamino General formula (III) is illustrated in figure 3: interaction of N-hydroxyphthalimide or tert-butyl-N-hydroxycarbonate with an alkylating agent, such as alkylhalogenide (LG-Y-A-R9), in a suitable solvent in the presence of a base, such as triethylamine, 1,8-diazabicyclo[5,4,0]-undec-7-ene (DBU), potassium carbonate or cesium carbonate, gives intermediate products obatala V or VI, respectively. Alternatively, you can spend interaction alcohol (LG LG-Y-A-R9=OH) N-hydroxyphthalimide in the reaction, such reaction Mitsunobu, in the presence of triphenylphosphine and diethylazodicarboxylate (DEAD) or diisopropylcarbodiimide in a suitable solvent, such as tetrahydrofuran or diethyl ether, obtaining the compounds of General formula V. the Interaction of V with hydrazine gives the required O-substituted (Y-A-R9) hydroxylamine General formula (III). Processing VI acid, for example triperoxonane acid or hydrochloric acid, gives the required O-substituted (Y-A-R9) hydroxylamine General formula (III). O-substituted (Y-A-R9) hydroxylamine General formula (III) can be extracted and used in the form of free amines or the corresponding salts, for example salts of hydrochloric acid, salts of Hydrobromic acid, or salts of sulfuric acid.

Scheme 3: how to obtain the O-substituted (Y-A) hydroxylamino General formula(III) (R1= H).

Acid of formula (II) in which W represents oxygen) can be obtained from the esters of General formula (VII) (where Q denotes, for example, alkyl or substituted alkyl) by hydrolysis, for example by hydrolysis, catalyzed by base, acid catalyzed or enzyme-mediated hydrolysis as shown in scheme 4. Neagr socialsim examples of grounds which can be used are lithium hydroxide, sodium hydroxide or potassium hydroxide.

Scheme 4: General method of obtaining the acids of General formula II from esters of General formula (VII)

Alternative acid of General formula (II) in which W represents oxygen) can be obtained by hydrolysis of the NITRILES of General formula (VIII), as shown in figure 5, for example basic, acidic or enzymatic hydrolysis.

Figure 5: a Common way to obtain the acid of General formula II from the NITRILES of General formula (VIII)

Esters of General formula (VII) can be obtained from the corresponding amines of General formula (IX) and aldehydes of General formula (X) (available from commercial sources or obtained, as for example described in WO 02/090352), for example by reductive amination (see, for example: A.F. Abdel-Magid, etc.: J. Org. Chem. (1996), 61, 3849-3862, WO 10 00/27819 and WO 02/090352), as shown in scheme 6. Suitable reducing agents are, for example, cyanoborohydride sodium, sodium borohydride or triacetoxyborohydride sodium. Amines of General formula IX can easily get a specialist in this area, or they are commercially available.

Scheme 6: a Common way to obtain esters of General formula (VII) of the amines of General formula (IX)

The NITRILES of formula (VIII) (for example, the where D denotes the nitrogen atom) can be obtained for example, the interaction of the compounds of General formula (XI) in which LG represents a suitable leaving group such as halogen, e.g. fluorine or chlorine) with amines of General formula (XII) (see, for example, R. Kwok. J. Heterocyclic Chem. (1978) 15, 877-880; S. Brunei and other J. Heterocyclic Chem. (1980) 17, 235-240), as shown in scheme 7. Compounds of General formula XI can easily get a specialist in this area, or they are commercially available.

Scheme 7: a General method of producing NITRILES of General formula (VIII) from NITRILES of General formula (XI)

GENERAL METHODS of OBTAINING AND EXAMPLES

Given as examples of compounds of General formula (I) are listed in table 1. For spectra1H nuclear magnetic resonance (NMR) (300 MHz) and13C NMR (75,6 MHz) the values of chemical shifts (δ) (in ppm) are given for solutions in dimethyl sulfoxide-d6(DMSO-d6) relative to the internal standard tetramethylsilane (δ=0). Values for multiplets, which are defined (doublet (d), triplet (t), Quartet (q)) or not defined (m)are approximately at the midpoint, if no range is specified, (users) refers to a broad singlet. Used organic solvents are anhydrous, until stated otherwise. The interaction is preferably carried out in an inert atmosphere, such as nitrogen or argon. Chromatography is performed on silica gel from Merck, 0,040-0,063 mm). Selected compounds or intermediates are commercially available, for example, from Aldrich, SPECS, Bionet research intermediates, Matrix or Lancaster. In the description uses the following abbreviations:

A saturated solution of saltA saturated aqueous solution of sodium chloride
Boctert-butoxycarbonyl
DMFN,N'-dimethylformamide
EtOActhe ethyl acetate
EQ.equivalent to
Mmolar (mol/l)
NMP1-methyl-2-pyrrolidinone
NMRnuclear magnetic resonance
THFtetrahydrofuran

Table 1:

Compounds of General formula (I) (W=oxygen: connection 1-399 and 402-432 R1= hydrogen, compound 400 R1= methyl)

Table 2:

Given as examples of intermediate products

General formula II

Table 3:

Given as examples of intermediate products

the General formula VIII

Table 4:

Given as examples of the substituted nitrogen

anhydrides of General formula XV

Table 5:

Given as examples Of substituted (Y-a) hydroxylamine General formula III

General method 1:

The synthesis of esters, hydroxamic acids of General formula (I) of the carboxylic acid of General formula (II).

Method 1:carboxylic acids of General formula (II) (1.0 EQ.) dissolved in anhydrous DMF or anhydrous NMP in an atmosphere of ar is she, receiving 0,2M solution or suspension. N,N'-Carbonyldiimidazole (1.0 EQ.) add one portion and the resulting reaction mixture was stirred at room temperature for 45-60 minutes Add O-substituted hydroxylamine (III) or the corresponding hydrochloride (1.0 EQ.) and continue stirring at room temperature for 20 hours. Add water and if the product precipitates, it is separated by filtration and recrystallized (usually ethanol). If the crude product is not precipitated as solids, the mixture is extracted with EtOAc. The combined organic layers washed with water and saturated salt solution, dried (MgSO4) and evaporated under reduced pressure. The residue is purified either by crystallization or by chromatography on silica gel (EtOAc/petroleum ether)to give esters, hydroxamic acids of General formula (I).

Method 2:carboxylic acid of General formula (II) (1.0 EQ.) dissolved in anhydrous DMF or anhydrous NMP in an argon atmosphere, getting 0,1-0,2M solution or suspension. O-Substituted hydroxylamine (III) or the corresponding hydrochloride (from 1.0 to 1.05 equiv.) 1-hydroxybenzotriazole hydrate (1,0-1,05 equiv.) N-methylmorpholine (2.0 EQ.) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.0 to 1.3 EQ.) add in that order. The reaction mixture was stirred at room temperature for 15-20 hours. Add the water mixture and the product extracted with EtOAc several times. The combined organic layers washed with water and saturated salt solution, dried (MgSO4or Na2SO4) and evaporated under reduced pressure. The crude product is purified either by chromatography on silica gel (typically using a mixture of EtOAc/petroleum ether as eluent), or by crystallization and recrystallization from a suitable solvent, such as ethanol or EtOAc, getting esters, hydroxamic acids of General formula (I).

A General method 1A:

The synthesis of esters, hydroxamic acids of General formula (I) from N-alkyl anhydrides of General formula (XV).

The mixture of the anhydride of General formula (XV) (1.0 EQ.) and O-substituted hydroxylamine (III) or the corresponding amine hydrochloride (1.1 EQ.) in pyridine (1-2 ml/mmol anhydride) was stirred at room temperature for 1-20 hours, or until, when LC/MS or TLC shows complete conversion of the educt. The solvent is evaporated under reduced pressure and dissolve the residue in EtOAc. The mixture is washed with water and saturated salt solution, dried (MgSO4or Na2SO4) and evaporated under reduced pressure. The crude product is purified either by chromatography on silica gel (usually using EtOAc/petroleum ether as solvent)or by crystallization and recrystallization from a suitable solvent, such as ethanol or EtAc, getting esters, hydroxamic acids of General formula (I).

General method 2:

Synthesis of carboxylic acids of General formula (II) from the corresponding esters of General formula (VII).

To a stirred 0,25M to a solution of ester of General formula (VII) (1.0 EQ.) in a mixture of THF/water (3:1, vol/about.) add lithium hydroxide (6-8 EQ.). The reaction mixture was stirred at room temperature for 60 min, then heated to 60°C and continue stirring at this temperature for 20 hours. The mixture is cooled to room temperature and evaporate the greater part of the solvent THF under reduced pressure. The residue is diluted with water and the pH of the mixture was adjusted to 5-6 by adding 4M hydrochloric acid. The obtained precipitated substance was separated by filtration and washed with water. Crystallization from ethanol gives a carboxylic acid of General formula (II).

General method 3:

Synthesis of carboxylic acids of General formula (II) from the corresponding NITRILES of General formula (VIII).

A suspension of the nitrile of General formula (VIII) in 27,65% sodium hydroxide (2.5 ml/mmol of nitrile) and methanol (1 ml/mmol of nitrile) is heated to boiling under reflux and stirred at this temperature for 3 hours. The mixture is cooled to room temperature and diluted with water. the pH of the mixture was adjusted to 5-6 by adding 4M hydrochloric acid. If a precipitate, it is separated Phi is trevanian, washed with water and dried in a high vacuum, getting a carboxylic acid of General formula (II). If the resulting acid residue, neutralized aqueous mixture is concentrated under reduced pressure and thoroughly extracted with ethyl acetate. The combined organic layers are dried

(MgSO4) and evaporated under reduced pressure. The residue is recrystallized from ethanol or methanol and receive a carboxylic acid of General formula (II).

Getting 1:

2-[(Pyridine-4-ylmethyl)amino]benzoic acid

General method 2 (alternate receipt described in WO 00/27819). Starting material: methyl ester of 2-[(pyridine-4-ylmethyl)amino]benzoic acid (P.W. Manley and others J. Med. Chem. (2002), 45, 5687-5693).13C-NMR (DMSO-d6) δ 169,69, 150,05, 149,35, 148,64, 134,03, 131,47, 121,70, 114,54, 111,30, 110,45, 44,41.

Obtaining 1A:

4-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid

To a stirred mixture of 2-amino-4-fermenting acid (Aldrich, 2.0 g) and pyridine-4-carbaldehyde (1,21 ml) in 1,2-dichloroethane (20 ml) add triacetoxyborohydride sodium (4.1 g). The reaction mixture was stirred at room temperature for 18 hours. Add silica gel and the solvent is evaporated under reduced pressure. The remainder chromatographic on a column of silica gel (elution with mixture of EtOAc/methane is l 19/1, about./about.) and get listed in the title compound (1.04 g).13C-NMR (DMSO-d6) δ 169,1, 166,2, 152,5, 149,6, 148,2, 134,6, 121,9, 107,6, 102,1, 97,7, 44,6.

Obtaining 1B:

2-Fluoro-6-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-6-fermenting acid (Aldrich) and pyridine-4-carbaldehyde.13C-NMR (DMSO-d6) δ 167,7, 162,7, 150,6, 149,5, 148,6, 133,8, 121,9, 107,3, 102,6, 101,9, 45,0.

Obtaining 1C:

5-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-5-fermenting acid (Aldrich) and pyridine-4-carbaldehyde.13C-NMR (DMSO-d6) δ 168,9, 152,4, 149,6, 148,8, 147,2, 121,9, 121,6, 116,6, 113,0, 110,7, 44,9.

Obtaining 1D:

3-Methoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid

Step 1: To a stirred solution of 3-methoxy-2-nitrobenzoic acid (11,50 g) in DMF (100 ml) is added N,N'-carbonyldiimidazole (11,35 g) and the reaction mixture was stirred at room temperature for 45 minutes Add methanol (18.6 ml) and the mixture is stirred at room temperature for 60 minutes the Mixture was poured into water (800 ml)containing ice, and the precipitated substance produce by filtration, crystallized from hot ethane is La and receive a methyl ester of 3-methoxy-2-nitrobenzoic acid. Stage 2: the result of the above methyl ester (11,81 g) suspended in water (45 ml) and ethanol (60 ml). Add the ammonium chloride of 12.26 g), and then iron powder (up 11,86 g). The reaction mixture is heated to boiling under reflux and stirred for 1 hour. The mixture is cooled in a bath with ice and then filtered through a layer of celite. The filtrate is evaporated under reduced pressure. The residue re-dissolved in minimum amount of EtOAc and filtered through a layer of silica gel, rinsing EtOAc. The combined filtrates evaporated under reduced pressure. The remaining oil was dissolved EtOAc (40 ml) and add hexane to the sediment. The solid is separated by filtration, dried in high vacuum and get methyl ester 2-amino-3-methoxybenzoic acid. Stage 3: the result of the above amine (7.5 g) was dissolved in 1,2-dichloroethane (125 ml) and added dropwise pyridine-4-carbaldehyde (6,65 g), and then triacetoxyborohydride sodium (17.5 g). The reaction mixture is heated to 50°C and stirred for 2.5 hours. Add pyridine-4-carbaldehyde (1.5 ml) and triacetoxyborohydride sodium 15 (5.0 g) and stirring is continued at 50°C for 15 hours. Carefully add saturated aqueous sodium bicarbonate and the mixture extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated salt solution, dried (MgSO4and viparis the Ute under reduced pressure. The remainder chromatographic on a column of silica gel (elution 0 to 50% EtOAc in dichloromethane) and receive the methyl ester of 3-methoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid as a pale yellow oil. Stage 4: the Compound obtained in stage 3 (8 g), dissolved in methanol (100 ml) and add 2M sodium hydroxide (50 ml). The reaction mixture is heated to 45°C and stirred for 1 hour. The mixture is cooled to room temperature and continue stirring for 18 hours. The mixture is concentrated to approximately 50 ml under reduced pressure. Add water (200 ml) and the pH of the mixture was adjusted to 6 4M HCl. The precipitated substance was separated by filtration, dried in vacuum and get listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 170,1, 150,3, 149,8, 149,3, 141,8, 123,4, 122,0, 117,0, 116,4, 114,8, 55,6, 48,4.

Getting 1E:

4,5-Dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-4,5-dimethoxybenzoic acid (Aldrich) and pyridine-4-carbaldehyde.13C-NMR (DMSO-d6) δ 169,4, 154,8, 149,6, 149,0, 147,5, 138,9, 122,1, 114,6, 101,4, 95,5, 56,1, 55,2, 45,0.

Receipt IF:

2-Methyl-6-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-6-methylbenzoic to the slots (Fluka) and pyridine-4-carbaldehyde. 13C-NMR (DMSO-d6) δ 170,4, 149,5, 149,3, 147,8, 138,5, 131,2, 121,9, 118,7, 115,8, 109,1, 45,1, 22,1.

Getting 1G:

5-Methyl-2-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-5-methylbenzoic acid (Aldrich) and pyridine-4-carbaldehyde.13C-NMR (DMSO-d6) δ 169,9, 149,5, 149,1, 148,3, 135,1, 131,5, 123,2, 121,9, 111,7, 110,5, 44,7, 19,6.

Obtaining 1H:

5-Bromo-2-[(pyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A from 2-amino-5-bromobenzoyl acid (Aldrich) and pyridine-4-carbaldehyde.13C-NMR (DMSO-d6) δ 170,4, 149,4, 149,4, 148,7, 133,9, 132,3, 123,2, 122,0, 112,2, 104,9, 44,9.

Getting 1I:

3-[(Pyridine-4-ylmethyl)amino]isonicotinoyl acid

Step 1: to a stirred solution of potassium tert-butylate (29,8 g) in DMSO (100 ml) is added 3-aminopyridine (10.0 g). Dark red reaction mixture is stirred at room temperature for 45 minutes, Add a solution of di-tert-BUTYLCARBAMATE (30,14 g) in DMSO (50 ml) and the reaction mixture was stirred at room temperature for 90 minutes the Mixture was poured into ice water and the pH of the mixture was adjusted to 6-7 by adding glacial acetic acid. The mixture is extracted with EtOAc. The organic layer washed the t water and saturated salt solution and evaporated under reduced pressure. The remaining oil is passed through a layer of silica gel, first rinsing with dichloromethane, then with a mixture of EtOAc/dichloromethane 1/1. The fractions containing the compound is evaporated under reduced pressure. The remaining oil is dissolved in diethyl ether (10 ml) and after addition of hexane (100-150 ml) get a solid substance was separated by filtration, and receive tert-butyl ether pyridine-3-ylcarbamate acid. Stage 2: carbamate, obtained in stage 1 (of 6.71 g), dissolved in THF (70 ml) and the mixture is cooled to -77°C. Add one drop of tert-utility (45 ml 1,7M solution in pentane) and continue stirring at -75°C for 2.5 hours. Dry gaseous CO2bubbled through the mixture at -75°C for 30 minutes the mixture is allowed to warm to room temperature and poured into ice water. The mixture is extracted with EtOAc and the pH of the aqueous layer was adjusted to 7-8 and perform a second extraction with EtOAc. Then bring the pH of the aqueous layer to 5-6 glacial acetic acid and obtained saducees substance separated by filtration and dried in high vacuum, getting 3-tert-butoxycarbonylmethylene acid (4,96 g). Stage 3: the acid (4,96 g)obtained in stage 2, was dissolved in DMF (70 ml) and add N,N'-carbonyldiimidazole (Android 4.04 g). The reaction mixture was stirred at room temperature for 45 min and add methanol (9.5 ml) and 4-dimethylaminopyridine (catalytics the second number). The mixture is stirred at room temperature for 2 hours. Add water and saducees substance separated by filtration, to obtain methyl ester 3-tert-butoxycarbonylmethylene acid (5.1 g). Stage 4: methyl ester (5.1 g), obtained in stage 3, heated to 185°C for 5 min Obtained brown substance suspended in EtOAc and filtered through a layer of silica gel, rinsing EtOAc. Add to the combined filtrates silica gel and the solvent is evaporated under reduced pressure. The compound containing silicon dioxide, heated to 160°C for 10 minutes the Mixture is cooled to room temperature, then heated to 160°C for another 10 minutes Then washed silica with 5% methanol in EtOAc. United leaching fraction is evaporated under reduced pressure and the oil obtained is treated with diethyl ether (10 ml) and hexane (70 ml) and receive the methyl ester of 3-aminoisoquinoline acid in the form of solids. Stage 5: Amin (2,27 g)obtained in stage 4, was dissolved in 1,2-dichloroethane (100 5 ml) and added dropwise pyridine-4-carbaldehyde (1.92 g) followed by the addition of triacetoxyborohydride sodium (6,32 g). The reaction mixture was stirred at room temperature for 4 hours and add saturated aqueous sodium bicarbonate. The mixture is extracted with dichloromethane and the organic layer is dried (MgSO4and viparis the Ute under reduced pressure. The remainder chromatographic on a column of silica gel (elution with 5% methanol in EtOAc) and receive the methyl ester of 3-[(pyridine-4-ylmethyl)amino]isonicotinic acid. Stage 6: compound (577 mg)obtained in stage 5, is dissolved in methanol (10 ml) and add 2M sodium hydroxide (10 ml). The mixture is stirred at room temperature for 15 min, the pH of the mixture was adjusted to 6 and is separated saducees substance by centrifugation and removal of solvent in vacuo. After drying in high vacuum, get mentioned in the title compound as a white fine powder.1H-NMR (DMSO-d6) δ 8,54 (d, 2H), 8,08 (s, 1H), 7,88 (d, 1H), to 7.64 (d, 1H), was 7.36 (d, 2H), and 4.68 (s, 2H).

Getting 1J:

2-(4-Forbindelsen)benzoic acid

To a stirred mixture of methyl ester of Anthranilic acid (5.0 g) and 4-forventelige (3.55 ml) in 1,2-dichloroethane (50 ml) add triacetoxyborohydride sodium (10.5 g). The reaction mixture was stirred at room temperature for 15 hours. Add saturated aqueous sodium bicarbonate. The layers are separated and the aqueous layer was extracted with 1,2-dichloroethane. The combined organic layers washed with water and saturated salt solution, dried (Na2SO4) and evaporated under reduced pressure. The remainder chromatographic on a column of silica gel (elution with mixture of EtOAc/petroleum ether 19) and obtain methyl ester of 2-(4-forbindelsen)benzoic acid (from 6.22 g). The obtained ether in turn specified in the title compound using the General method 2.13C-NMR (DMSO-d6) δ 169,9, 161,1, 150,4, 135,5, 134,3, 131,6, 128,9, 115,2, 114,5, 111,6, 110,4, 45,0.

Getting 1K:

2-(3-Cyano-4-forbindelsen)benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 2-fluoro-5-formylbenzoate (Aldrich).13C-NMR (DMSO-d6) δ 172,1, 161,3, 149,5, 138,7, 134,6, 131,9, 130,2, 121,4, 116,6, 114,2, 114,0, 110,0, 99,8, 44,8.

Obtaining 1L:

Methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid

2-Fluoro-5-formylbenzoate acid (ABCR, 1.0 g) dissolved in benzene (10 ml) and methanol (5 ml) and cooled to 0-5°C.

Add one drop of (trimethylsilyl)diazomethane (6,0 ml of 2M solution in hexane) over 20 minutes, the Reaction mixture was stirred for 30 min at 5°C and the solvent is evaporated under reduced pressure, obtaining the methyl ester of 2-fluoro-5-formylbenzoate acid, which is used without further purification. The crude ester in turn specified in the title compound, using a technique similar to that described for obtaining 1A, by reductive amination of Anthranilic acid.13C-NMR (DMSO-d6) δ 169,9, 163,9, 159,8, 150,3, 136,1, 134,3, 133,5, 131,7, 129,9, 117,9, 117,1, 114,7, 111,6, 110,5, 52,3, 4,6.

Getting 1M:

2-(4-Methoxybenzylamine)benzoic acid

Get the method similar to that described to obtain 1J, based on the methyl ester of Anthranilic acid and 4-methoxybenzaldehyde.13C-NMR (DMSO-d6) δ 169,9, 158,2, 150,6, 134,2, 131,6, 131,0, 128,3, 114,3, 113,9, 111,6, 110,2, 54,9, 45,3.

Getting 1N:

2-[(4-Methoxynaphthalene-1-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 4-methoxy-1-naphthaldehyde (Aldrich).13C-NMR (DMSO-d6) δ 169,9, 154,4, 150,7, 134,4, 131,8, 131,6, 126,7, 125,8, 125,7, 125,2, 125,1, 123,3, 122,0, 114,4, 111,6, 110,1, 103,7, 55,4, 43,9.

Getting 1O:

2-[(2,3-Dihydrobenzofuran-5-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 2,3-dihydrobenzo[b]furan-5-carboxaldehyde (Matrix).13C-NMR (DMSO-d6) δ 169,9, 158,7, 150,6, 134,3, 131,6, 130,9, 127,5, 126,8, 124,0, 114,3, 111,5, 110,1, 108,6, 70,8, 45,6, 29,0.

Getting 1P:

2-[(Benzofuran-5-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 1-benzofuran-5-carbaldehyde (Maybridge).13C-NMR (DMSO-d6) δ 169,9, 153,5, to 150.6, 46,3, 134,3, 133,9, 131,6, 127,3, 123,6, 119,5, 114,4, 111,6, 111,2, 110,2, 106,6, 45,8.

Getting 1Q:

2-[(2-Oxo-2H-chromen-6-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and coumarin-6-carbaldehyde (Matrix).13C-NMR (DMSO-d6) δ 169,9, 159,9, 152,5, 150,4, 144,1, 135,8, 134,3, 131,7, 130,7, 126,4, 118,6, 116,4, 116,3, 114,6, 111,6, 110,5, 45,0.

Getting 1R:

2-[(3,5-Dichloropyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1J, based on the methyl ester of Anthranilic acid and 3,5-dichloro-4-pyridinecarboxamide (Aldrich).13C-NMR (DMSO-d6) δ 170,1, 149,7, 147,9, 142,6, 133,5, 132,2, 131,7, 115,1, 113,2, 110,9, 41,4.

Getting 1S:

2-[(2-Bromopyridin-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 2-bromopyridin-4-carbaldehyde (obtained as described in WO 2004/013102 A1).13C-NMR (DMSO-d6) δ 169,8 153,3, 150,4, 149,9, 141,5, 134,3, 131,7, 125,8, 121,6, 115,0, 111,5, 110,8, 44,1.

Getting 1T:

2-[(2-Hydroxypyridine-4-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 2-hydrox the-4-pyridinecarboxamide (Tyger). 13C-NMR (DMSO-d6) δ 169,8, 162,4, 153,6, 150,2, 135,0, 134,2, 131,6, 115,8, 114,7, 111,5, 110,5, 104,0, 44,7.

Getting 1U:

2-[(2-Morpholine-4-espiridion-4-ylmethyl)amino]benzoic acid

Stage 1: palladium(II) acetate (324 mg) and racemic 2,2'-bis(diphenylphosphino)-1,1'-dinately (899 mg) suspended in toluene (100 ml) and the mixture to remove oxygen. Add morpholine (3.77 ml) and tert-butyl sodium (4,85 g) and the mixture is heated to 50°C. Add portions 2-horizontalmente (5.0 g) for 15 min and the resulting reaction mixture was stirred at 50°C for 24 hours. The mixture is cooled to room temperature and filtered through a thin layer of celite, washing with excess EtOAc. The combined filtrates evaporated under reduced pressure and the remaining solid is recrystallized from ethanol and receive 2-morpholine-4-isonicotinoyl in the form of a yellow crystalline substance (3,91 g). Stage 2: the compound obtained in stage 1 (379 mg), dissolved in toluene and cooled to -30°C. was Added drop diisobutylaluminium (1.7 ml 1,2M solution in toluene) and the reaction mixture is allowed slowly to warm to -15°C and stirred at this temperature for 60 minutes Add glacial acetic acid (1.0 ml) and removing the cooling bath. Water is added and the mixture is stirred at room temperature for 2.5 hours. The mixture is diluted with EtOAc and pods lacivious, adding 2M sodium hydroxide. Add a solution of tartrate of sodium/potassium and separate the layers. The organic layer was washed with saturated salt solution, dried (Na2SO4) and evaporated under reduced pressure and get 2-morpholine-4-espiridion-4-carbaldehyde which is used without further purification. Stage 3: the crude aldehyde obtained in stage 2, in turn specified in the title compound interaction with Anthranilic acid using a method similar to that described to obtain 1A.13C-NMR (DMSO-d6) δ 169,9, 159,3, 150,5, 150,3, 147,5, 134,3, 131,6, 114,7, 112,0, 111,6, 110,4, 104,9, 65,8, 45,3, 45,1.

Getting 1V:

2-[(Quinoline-4-ylmethyl)amino]benzoic acid

A solution of Anthranilic acid (5,46 g) in methanol is added to the melt quinoline-4-carbaldehyde (6,26 g) and the mixture is heated on a water bath for 6 hours. The mixture is cooled to room temperature and the solid is separated by filtration and washed with methanol, obtaining 2-[(quinoline-4-ylmethylene)amino]benzoic acid (10,33 g). This intermediate product (10.3 g) was dissolved in THF and ethanol and added in portions sodium borohydride (1,41 g). The reaction mixture was stirred at room temperature for 3 hours. Add sodium borohydride (1,41 g) and a small amount of methanol and continue stirring at room is the temperature for 4 hours. The mixture is evaporated under reduced pressure and transferred into a separating funnel with the aid of EtOAc and water. The layers are separated and the aqueous layer was neutralized by adding 4M hydrochloric acid. Received saducees substance separated by filtration, washed with water and dried in vacuum, obtaining specified in the header connection (7,1 g).13C-NMR (DMSO-d6) δ 170,4, 150,3, 150,3, 147,6, 144,8, 133,4, 131,7, 129,6, 129,2, 126,5, 126,1, 123,5, 118,5, 114,6, 112,9, 111,2, 42,7.

Obtaining 1W:

2-[(6-Methoxypyridine-3-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1A, based on Anthranilic acid and 2-methoxypyridine-5-carboxaldehyde (Aldrich).13C-NMR (DMSO-d6) δ 169,9, 162,9, 150,4, 145,7, 138,6, 134,4, 131,7, 127,7, 114,7, 111,7, 110,5, 110,5, 53,1, 42,8.

Getting 1X:

2-[(Thiazol-5-ylmethyl)amino]benzoic acid

Get the method similar to that described to obtain 1J, based on the methyl ester of Anthranilic acid and thiazole-5-carboxaldehyde (Combi-Blocks).13C-NMR (DMSO-d6) δ 169,8, 153,6, 149,9, 140,8, 137,9, 134,3, 131,6, 115,0, 111,6, 110,7, 38,3.

Getting 1Y:

2-[(Tetrahydropyran-4-ylmethyl)amino]benzoic acid

To stir the mixture satiago anhydride (2.5 g) and triphenylphosphine (4.0 g) in THF (100 ml) at 0°C was added drop diisopropyl azodicarboxylate (3.0 ml), and then (tetrahydropyran-4-yl)methanol (1.78 g). The reaction mixture was stirred at room temperature for 15 hours and the solvent is evaporated under reduced pressure. The remainder chromatographic on a column of silica gel (EtOAc/petroleum ether, 9/1), receiving contaminated 1-(tetrahydropyran-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione. This substance is treated with 27% sodium hydroxide (20 ml) at 50°C for 48 hours. The mixture is cooled to room temperature and added 37% hydrochloric acid (15 ml). The mixture is extracted with EtOAc several times and the combined organic layers washed with water, dried (Na2SO4) and evaporated under reduced pressure. The residue is purified by the method of column chromatography on silica (EtOAc/petroleum ether, 2/8) and receive specified in the header of the connection.13C-NMR (DMSO-d6) δ 170,0, 151,0, 134,4, 131,6, 113,9, 111,2, 109,7, 66,7, 47,8, 34,1, 30,4.

Getting 2:

2-[(Pyridine-4-ylmethyl)amino]nicotinic acid

General method 3. Starting material: 2-[(pyridine-4-ylmethylamino]benzoic acid (see obtaining 5).13C-NMR (DMSO-d6) δ 168,75, 157,91, 153,01, 149,64, 149,27, 140,13, 121,94, 111,67, 106,50, 42,69.

Getting 3:

2-(4-Forbindelsen)nicotinic acid

General method 3. Starting material: 2-(4-forbindelsen)nicotinamide (with the Autry obtaining 6). 1H-NMR (DMSO-d6) δ 13,07 (users, 1H), of 8.47 (users, 1H), 8,25 (DD, 1H), 8,10 (DD, 1H), 7,34-7,39 (m, 2H), 7,10-7,16 (m, 2H), 6,63 (DD, 1H), 4,67 (d, 2H).

Obtaining 3A:

2-(4-Chlorobenzylamino)nicotinic acid

Get the method similar to that described for the preparation of 3 based on 2-(4-chlorobenzylamino)nicotinanilide (obtained from 2-chloronicotinoyl and 4-chlorobenzylamino, using a technique similar to that described for obtaining 6).1H-NMR (DMSO-d6) to 13.09 δ (user., 1H), 8,51 (user., 1H), 8,23 (DD, 1H), 8,09 (DD, 1H), 7,40-7,30 (m,4H), 6,63 (DD, 1H), and 4.68 (d, 2H).

Obtaining 3B:

2-(Isoquinoline-5-ylamino)nicotinic acid

To a stirred solution of 5-aminoisoquinoline (526 mg) in DMF (20 ml) at 0-5°C add sodium hydride (400 mg 55-65% dispersion in mineral oil). The cooling bath is removed and stirred the dark green reaction mixture at room temperature for 30 minutes Add 2-chloronicotinamide (506 mg) and the mixture is stirred at room temperature for 12 hours. The reaction is quenched by adding water and the products extracted with EtOAc several times. The combined organic layers washed with water and 3M CaCl2, dried (MgSO4) and evaporated under reduced pressure. The remaining red-brown solid is recrystallized from ethanol and receive 2-(isoquinoline-5-yl) - Rev. Mino)nicotinamide (306 mg): 13C-NMR (DMSO-d6) δ 157,6, 152,4, 152,4, 143,1, 142,5, 135,0, 132,1, 129,0, 127,2, 126,9, 125,1, 116,5, 116,3, 114,3, 92,5.

The above compound nitrile in turn specified in the title compound using the General method 3.

Getting 4:

2-(4-Methoxybenzylamine)nicotinic acid

General method 3. Starting material: 2-(4-methoxybenzylamine)nicotinamide (see obtaining 7).13C-NMR (DMSO-d6) δ 168,83, 158,11, 157,96, 153,19, 140,06, 131,74, 128,55, 113,69, 111,21, 105,95, 54,92, 43,16.

Getting 5:

2-[(Pyridine-4-ylmethylamino]nicotinamide

To a stirred solution of 2-chloronicotinoyl (Aldrich, 10.4 g, 75,06 mmol) in anhydrous NMP (40 ml) is added 4-(aminomethyl)pyridine (15.2 ml, 150,26 mmol). The reaction mixture is heated to 130°C and stirred at this temperature for 20 hours. The mixture is cooled to room temperature, diluted with EtOAc (500 ml) and washed with saturated aqueous NaHCO3, water and saturated salt solution. The organic layer is dried (Na2SO4) and evaporated under reduced pressure. The remaining red-brown solid is recrystallized from ethanol, getting mentioned in the title compound (7,73 g) as off-white solid. The filtrate is evaporated under reduced pressure, re-dissolved in a mixture of 2% methanol/EtOAc (about./about.) and f is trout through a layer of silica gel. The filtrate is evaporated under reduced pressure and the residue is recrystallized from ethanol and receive an additional amount specified in the connection header (2,44 g).13C-NMR (DMSO-d6) δ 157,80, 152,65, 149,30, 149,10, 142,49, 121,94, 116,65, 112,09, 90,62, 43,00.

Getting 6:

2-(4-Forbindelsen)nicotinamide

To a stirred suspension of 2-chloronicotinamide (Aldrich, 3,30 g, 23,82 mmol) in 2-propanol (30 ml) is added 4-forbindelsen (3,00 ml, 26,25 mmol) and N,N-diisopropylethylamine (8,30 ml, 47,65 mmol). The reaction mixture is heated to 80°C for 24 hours. Add another 4-forbindelsen (0,55 ml, to 4.81 mmol) and continue stirring at 80°C for 24 hours. The reaction mixture is cooled to room temperature and saducees substance separated by filtration and washed with 2-propanol. The remains of 2-propanol is removed in vacuum, obtaining mentioned in the title compound (3.04 from g) as a white crystalline substance.1H-NMR (DMSO-d6) δ 8,23 is 8.25 (m, 1H), to $ 7.91 (DD, 1H), 7,73 (t, 1H), 7,34-7,38 (m, 2H), 7,08-7,14 (m, 2H), 6,63 is 6.67 (m, 1H), 4,57 (d, 2H).

Getting 7:

2-(4-Methoxybenzylamine)nicotinamide

To a stirred mixture of 2-chloronicotinamide (Aldrich, 2.20 g, 15,88 mmol) and 4-methoxybenzylamine of 2.27 ml, 17,49 mmol) in 2-propanol (20 ml) is added N,N-diisopropylethylamine (of 5.53 ml, 31,75 mmol). React the mixture was heated to 80°C and stirred at this temperature for 24 hours. Add another 4-methoxybenzylamine (0,50 ml of 3.85 mmol) and continue stirring at 70°C for 48 hours. The mixture is cooled to room temperature and the resulting solid (4-methoxybenzylideneamino) removed by filtration. When standing in the filtrate formed crystalline product is separated by filtration, washed with 2-propanol and dried under reduced pressure, obtaining mentioned in the title compound as light yellow crystals (1.27 g).13C-NMR (DMSO-d6) δ 8,21-8,30 (m, 1H), of 7.90 (d, 1H), 7,65 (t, 1H), 7,25 (d, 2H), 6,85 (d, 2H), 6,59 of 6.68 (m, 1H), 4,50 (d, 2H, in), 3.75 (s, 3H).

Obtaining 7A:

1-Pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione

To stir the mixture satiago anhydride (72,60 g, 445,0 mmol) and triphenylphosphine (116,74 g, 445,1 mmol) in THF (1 l) at 0°C was added drop diisopropylsalicylic approximately 50 minutes of the Obtained light-yellow reaction mixture was stirred for 10 min before adding one drop of a solution of 4-hydroxymethylbenzene (48,57 g, 445,1 mmol) in THF (250 ml). The reaction mixture was stirred at room temperature for 2 hours. The obtained red solution is filtered through a layer of silica gel and the filtrate is evaporated under reduced pressure. The residue is treated with EtOAc and the resulting saducees substance separated by filtration and recrystallized from EtAc, getting listed in the title compound as a white solid (37.5 g). The filtrate from the crystallization extracted with 0,1M aqueous HCl. the pH of the aqueous layer was adjusted to 7-8 with saturated aqueous sodium bicarbonate. Saducees substance separated by filtration and washed with water, getting mentioned in the title compound (9.8 g). The combined aqueous filtrate is extracted with EtOAc several times. The combined organic layers evaporated under reduced pressure. The residue is recrystallized from EtOAc, receiving the additional amount specified in the connection header (20,3 g).13C-NMR (DMSO-d6) δ 158,7, 149,7, 148,2, 144,5, 141,1, 136,9, 129,5, 123,8, 121,5, 114,8, 112,1, 46,7.

Getting 7B:

1-(2-Aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione

To a stirred mixture of 2-aminopyridine-4-methanol (commercially available from CB Research, 25,05 g, 201,79 mmol) satiago anhydride (32,91 g/201,74 mmol) and triphenylphosphine (52,92 g, 201,76 mmol) in THF (400 ml) at 20°C add drop by drop diisopropylsalicylic (40,8 g, 201,77 mmol). The reaction mixture was stirred at room temperature for 1 hour. The mixture is cooled to 0°C and saducees substance separated by filtration and washed with a small amount of THF, getting mentioned in the title compound as a yellow solid (18,93 g). The filtrate is evaporated, propanganda pressure. To the residue oil was added dichloromethane. The obtained precipitate was separated by filtration, getting more product (1,21 g). The filtrate is extracted with 0,1M aqueous HCl and the pH of the aqueous layer was adjusted to about 7-8 aqueous sodium bicarbonate, and then extracted with EtOAc. The organic layer is evaporated under reduced pressure and the resulting solid is suspended in THF (100 ml). The solid is separated by filtration, getting more product (9,10 g). The filtrate is concentrated to about 45 ml of getting the precipitate and the additional amount specified in the connection header (1,77g) after filtration and drying in vacuum.13C-NMR (DMSO-d6) δ 160,0, 158,7, 148,1, 148,0, 145,0, 141,2, 137,1, 129,5, 123,8, 115,0, 111,7, 109,9, 104,5, 46,8.

Getting 7C:

Pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid

To a stirred suspension of 2-[(pyridine-4-ylmethyl)amino]benzoic acid (receiving 1, 300 mg) in EtOAc (10 ml) add 2,3,4,5,6-pentafluorophenol (413 mg), and then drop by drop a solution of N,N-dicyclohexylcarbodiimide (461 mg) in EtOAc (5 ml). The reaction mixture was stirred at room temperature for 15 hours. The formed precipitate is removed by filtration and the filtrate is evaporated under reduced pressure. The remaining substance chromatographic by column on silica gel (petroleum ether/EtOAc as eluent) and get listed in the title the information compound (352 mg). 13C-NMR (DMSO-d6) δ 163,2, 151,4, 149,7, 148,1, 140,9, 138,9, 137,6, 136,9, 131,9, 124,7, 121,9, 115,6, 112,5, 105,5, 44,7.

Obtaining 7D:

4-(2,4-Dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)benzonitrile

To stir the mixture satiago anhydride (2.0 g) and 4-cyanobenzaldehyde (2,40 g) in DMF (20 ml) is added drop by drop of 1,8-diazabicyclo[5,4,0]undec-7-ene (2.20 ml). The reaction mixture was stirred at room temperature for 22 h, cooled in a bath with ice and add water (75 ml). Received saducees substance separated by filtration, recrystallized from hot toluene and get listed in the title compound (1.65 g) as off-white solid.13C-NMR (DMSO-d6) δ 158,7, 148,2, 141,2, 141,1, 136,9, 132,4, 129,5, 128,8, 128,1, 127,5, 123,7, 118,6, 114,8, 112,2, 110,2, 47,3.

Getting 7E:

1-(5-Oxo-4,5-dihydro-1H-[1,2,4l-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione

To a stirred suspension of semicarbazide (5,69 g) in methanol (100 ml) is added 2-chloro-1,1,l-trimethoxymethane (of 13.75 ml). The reaction mixture was stirred at room temperature for 3 days. Received almost clear solution is filtered and the filtrate is evaporated under reduced pressure. The residue is suspended in toluene and unknown substance was separated by filtration and washed with toluene, receiving 5-chloromethyl-2,4-digit the-[1,2,4]triazole-3-one (6,1 g). This compound in turn is specified in the title compound interaction with sativum anhydride, using the same methodology as described for obtaining 7D.13C-NMR (DMSO-d6) δ 158,7, 156,0, 147,9, 142,5, 141,1, 137,4, 129,6, 124,2, 114,7, 111,8, 40,6.

Getting 7F:

1-(2-Imidazol-1-retil)-1H-benzo[d][1,3]oxazin-2,4-dione

Get the method similar to that described to obtain 7B, on the basis of satiago anhydride and 1-(2-hydroxyethyl)imidazole (Fluorchem).13C-NMR (DMSO-d6) δ 158,7, 147,5, 141,3, 137,6, 136,9, 129,4, 128,5, 123,6, 119,7, 114,0, 111,3, 45,1, 43,3.

Getting 7G:

1-(1-Pyridine-4-retil)-1H-benzo[d][1,3]oxazin-2,4-dione

Get the method similar to that described to obtain 7A, based on satiago anhydride and (+/-)-1-(4-pyridyl)ethanol (Fluka).13C-NMR (DMSO-d6) δ 159,0, 149,8, 148,6, 140,6, 136,5, 129,8, 123,6, 121,2, 115,7, 112,9, 53,1, 15,4.

Getting 7H:

6-Oxo-1,6-dihydropyridines-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione

Get the method similar to that described to obtain 7B, on the basis of satiago anhydride and 5-hydroxymethyl-1H-pyridine-2-it (obtained as described in WO 01/77078 Al).13C-NMR (DMSO-d6) δ 162,0, 158,9, 148,4, 141,2, 140,9, 137,0, 134,1, 129,5, 123,7, 120,1, 115,0, 112,3, 112,0, 44,3.

Getting 7I:

1-(6-Oxo-1,6-dihydropyridines-3-ylmethyl)-1H-pyrid the[2,3-d][1,3]oxazin-2,4-dione

Can be obtained by the method similar to that described to obtain 7B, on the basis of 1H-pyrido[2,3-d][1,3]oxazin-2,4-dione (can be obtained, as described Beckwith and Hickman in the work of J. Chem. Soc. (C), 1968, pp 2756-2759) and 5-hydroxymethyl-1H-pyridine-2-it (obtained as described in WO 01/77078 Al).

Getting 8:

Hydrochloride, O-(3,4,5-trimethoxybenzyl)hydroxylamine

To a stirred solution of 3,4,5-trimethoxybenzylamine (1,00 g, 4.6 mmol) and tert-butyl-N-hydroxycarbonate (of 0.62 g, 4.6 mmol) in acetonitrile (20 ml) add Cs2CO3(4,51 g of 13.8 mmol). The reaction mixture was stirred at room temperature for 24 hours. Add water and the products extracted with EtOAc twice. The combined organic extracts washed with water and saturated salt solution, dried (MgS04) and evaporated under reduced pressure. The crude product is purified by chromatography on silica using a gradient of EtOAc in petroleum ether (0-40%, vol./about.) and getting 411 mg of Boc-protected O-(3,4,5-trimethoxybenzyl)hydroxylamine. This intermediate product (383 mg, 1,22 mmol) is treated with 37% hydrochloric acid (2.5 ml) in EtOAc (7.5 ml) for 30 min at room temperature. The mixture is concentrated under reduced pressure and add diethyl ether. Received saducees substance separated by filtration and su is at high vacuum, getting listed in the title compound (211 mg) as white shiny crystals.1H-NMR (DMSO-d6) δ 11,10 (users, 3H), 6,76 (s, 2H), to 4.98 (s, 2H), 3,79 (s, 6H), to 3.67 (s, 3H).

9:

Hydrochloride, O-(4-Chlorobenzyl)hydroxylamine

The technique is similar to the procedure described to obtain 8. Educt: 4-Chlorobenzilate and tert-butyl-N-hydroxycarbonate.1H-NMR (DMSO-d6) δ 11,18 (users, 3H), 7,44-7,51 (m, 4H), of 5.06 (s, 2H).

10:

Hydrochloride, O-(4-cyanobenzyl)hydroxylamine

N-Hydroxyphthalimide (3,30 g, 20,mmol) dissolved in NMP (50 ml) and add 4-cyanobenzeneboronic (4.35 g, of 22.2 mmol), and then one drop of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (3.0 ml, of 20.1 mmol). Upon completion of the addition of DBU (about 15 min) the reaction mixture was stirred at room temperature for 65 minutes the Mixture was poured on ice, chilled 1M aqueous hydrochloric acid (500 ml) and saducees substance produce by filtration, washed with water and dried in high vacuum. This phthalimide derived (5.31g, 19,1 mmol) suspended in ethanol (40 ml) and added drop by drop a solution of hydrazine monohydrate (0,93 ml of 19.1 mmol) in ethanol (10 ml). The reaction mixture is heated to boiling under reflux and stirred for 2.5 hours. The mixture is cooled to room temperature awardee substance is removed by filtration and washed with ethanol. The combined filtrates evaporated under reduced pressure. The residue re-suspended in EtOAc and undissolved matter is removed by filtration. EtOAc-filtrate washed with saturated aqueous NHCO3and water, dried (MgSO4) and evaporated under reduced pressure. The residue is suspended in diethyl ether (150 ml), add concentrated hydrochloric acid (50 ml) and the resulting paste is stirred at room temperature for 30 minutes Usageprice the product is separated by filtration, washed with diethyl ether and dried in vacuum, obtaining mentioned in the title compound (2.24 g) as a white powder.1H-NMR (DMSO-d6) of 11.26 δ (users, 3H), of 7.90 (d, 2H), 7,63 (d, 2H), 5,17 (s, 2H).

Obtaining 11:

O-Quinoline-2-almatygidrogeologiya

Tert-Butyl N-hydroxycarbonate (1,00 g, 7,51 mmol) dissolved in DMF (25 ml) and the mixture cooled in an ice bath. Add sodium hydride (655 mg 55-65% dispersion in mineral oil) and after 20 min add portions 2-chlormethylphenylketone (1.6 g, 7,50 mmol). The cooling bath is removed and the reaction mixture was stirred at room temperature for 20 hours. The reaction is quenched by adding water and the product extracted with EtOAc. The combined organic layers washed with water and saturated salt solution, dried (MgSO4) and evaporated under reduced pressure. The floor is built of yellow oil decanted petroleum ether and the product is crystallized from a mixture of EtOAc/petroleum ether, receiving N-Boc-protected O-quinoline-2-almatygidrogeologiya (881 mg) as a pale yellow solid.13C-NMR (DMSO-d6) δ 157,12, 156,19, 146,78, 136,44, 129,60, 128,53, 127,78, 127,18, 126,48, 120,31, 79,81, 78,38, 27,89. This substance (860 mg, 3.14 mmol) was dissolved in CH2Cl2(10 ml) and add triperoxonane acid (4.4 ml). The reaction mixture was stirred at room temperature for 60 min and the solvent is evaporated under reduced pressure. The residue is dissolved in EtOAc and washed with saturated aqueous NaHCO3, dried (MgSO4) and evaporated under reduced pressure. This gives specified in the title compound (376 mg) as a yellow oil which is used without further purification.

Obtaining 12:

Hydrochloride, O-(2-methylthiazole-4-ylmethyl)hydroxylamine

N-Hydroxyphthalimide (15.2 g) was dissolved in DMF (120 ml) and add 4-chloromethyl-2-methylthiazole (18,4 g). The mixture is cooled in an ice bath and add drop by drop a solution of triethylamine (28,6 ml) in DMF (30 ml). The cooling bath is removed and the reaction mixture was stirred at room temperature for 3 days. The mixture was poured into water (600 ml) and saducees substance separated by filtration, washed with water and dried in vacuum. This interim phthalimide (21,4 g) is refluxed in ethanol (150 ml)containing n-butylamine (7.7 ml)during the 2.5 hours. The mixture is cooled to room temperature and added 4M hydrochloric acid in diethyl ether (25 ml). The mixture is left at 0-5°C over night and received saducees substance separated by filtration and washed with cold ethanol and diethyl ether, obtaining mentioned in the title compound (11.2 g) as a white crystalline substance.13C-NMR (DMSO-d6) δ 166,85, 147,15, 121,35, 70,03, 18,37.

13:

Hydrochloride, O-(4-fluoro-2,6-dimethylbenzyl)hydroxylamine

To a stirred solution of 2,6-dimethyl-4-ftorangidridy (4,89 g of 22.5 mmol) in DMF (100 ml) is added N-hydroxyphthalimide (3,67 g of 22.5 mmol), and then drop the triethylamine (3.5 ml, 25,1 mmol). The reaction mixture was stirred at room temperature for 2 hours. The mixture is then poured into 1M aqueous HCl and the resulting white precipitate was separated by filtration, washed with water and dried in vacuum. This interim phthalimide (6,51 g, 21.9 mmol) is treated with hydrazine monohydrate (of 1.06 ml, and 21.8 mmol) in ethanol (60 ml) by boiling under reflux for 3 hours. The mixture is cooled to room temperature and add the ether. Saducees substance is removed by filtration and the filtrate is evaporated under reduced pressure. The residue is suspended in EtOAc and filtered. Add to the filtrate 4M HCl in dioxane (22 mmol) and the resulting precipitate was separated by filtration, dried in vacuum and get the specified header connection (to 3.92 g) in the form of a white powder. 13C-NMR (DMSO-d6) δ 161,9, 141,8, 126,5, 114,3, 69,3, 19,2. Alternatively, the intermediate phthalimide can be treated with hydrazine monohydrate (1 EQ.) in dichloromethane at room temperature for 20-24 hours, to remove the formed solid by filtration and evaporate the filtrate, and obtaining a free hydroxylamine.

Obtaining 14:

Hydrochloride, O-(4-fluoro-2-methoxybenzyl)hydroxylamine

Fluoro-2-methoxybenzaldehyde (Fluorochem, 4,5g) was dissolved in methanol (40 ml) and cooled to 0°C. Add sodium borohydride (1.1 g) and the mixture is stirred for 1 hour. Add water (200 ml) and the mixture is concentrated under reduced pressure (about 100 ml). The obtained precipitate was separated by filtration, washed with water, dried in vacuum and get 4-fluoro-2-methoxyphenyl)methanol (3,76 g). This alcohol (3,76 g) dissolved in THF (100 ml) and add N-hydroxyphthalimide (3,93 g) and triphenylphosphine (6,32 g), and then drop diisopropylsalicylic (4,87 g). The obtained turbid red reaction mixture is stirred at room temperature for 30 minutes the Mixture is filtered through a layer of silica gel and the filtrate is evaporated under reduced pressure. Add to the residue ethanol (70 ml), and it dissolves when heated. Upon cooling forms crystalline substance separated by filtration and dried in vacuum. This Prohm is filling phthalimide (6,15 g) is suspended in ethanol (50 ml) and added hydrazine monohydrate (1.0 ml), dissolved in ethanol (10 ml). The reaction mixture is heated at boiling under reflux and stirred for about 3 hours. The mixture is cooled to room temperature and removed by filtering the solid. The filtrate is evaporated under reduced pressure and the residue treated with EtOAc and filtered. Add to the filtrate 4M HCl in dioxane (1.0 EQ.), received saducees substance separated by filtration and receive specified in the header connection (3,26 g) as a white solid.13C-NMR (DMSO-d6) δ 163,7, 159,2, 132,6, 117,8, 106,6, 99,7, 70,2, 56,0.

Obtaining 15:

O-(2,3-Debtor-4-methylbenzyl)hydroxylamine hydrochloride and

To a stirred solution of 2,3-debtor-4-methylbenzylamine (Matrix of 10.47 g) and N-hydroxyphthalimide (7,73 g) in DMF (100 ml) was added drop triethylamine (Et3N) (7.3 ml) (as an alternative to Et3N you can use DBU). The red reaction mixture is stirred at room temperature for 2 hours. After addition of 1M aqueous HCl a white precipitate is formed, which is separated by filtration, washed with water and dried in vacuum, obtaining the intermediate phthalimide (12,55 g, brilliant white matter). This compound (6,07 g) is dissolved in dichloromethane and added drop by drop methylhydrazine (1,16 ml). The reaction mixture was stirred at room temperature for 30 m is h and the solid is removed by filtration. The filtrate is evaporated under reduced pressure and purified by chromatography on silica gel (mixture of EtOAc/petroleum ether as eluent), get listed in the title amine as a clear, colorless oil (3,34 g). Alternatively, the intermediate phthalimide can be treated with hydrazine monohydrate (1.0 EQ.) in boiling under reflux ethanol for 2-3 hours and get listed in the title compound as hydrochloride salt in the processing of 4M HCl in dioxane as described above to obtain 14. HCl-salt:13C-NMR (DMSO-d6) δ 150,0, 146,8, 128,4, 126,2, 126,1, 120,3, 68,9, 13,9. The free amine:13C-NMR (DMSO-d6) δ 149,2, 149,3, 127,0, 125,4, 124,5, 124,0, 70,9, 14,3.

Obtaining 16:

Hydrochloride, O-(3-fluoro-4-methylbenzyl)hydroxylamine

Get analogously to the method described in 13, from 3-fluoro-4-methylbenzylamine (Fluorochem) and N-hydroxyphthalimide.13C-NMR (DMSO-d6) δ 160,4, 133,5, 131,7, 124,9, 115,5, 74,6, 13,9.

Obtaining 17:

Hydrochloride, O-(5-fluoro-2-methylbenzyl)hydroxylamine

Get analogously to the method described in 13, starting from 5-fluoro-2-methylbenzylamine (Apollo) and N-hydroxyphthalimide.13C-NMR (DMSO-d6) δ 160,1, 133,8, 133,7, 131,9, 116,6, 115,7, 73,2, 17,6.

Obtaining 18:

Hydrochloride, O-(2,3,5,6-titrator-4-methoxybenzyl)hydroxyl is and

To a stirred solution of N-hydroxyphthalimide (2.15 g) and 2,3,5,6-titrator-4-methoxybenzylamine (Apollo, of 3.96 g) in NMP (30 ml) is added drop by drop of 1,8-diazabicyclo[5,4,0]-undec-7-ene (1.97 ml). The obtained transparent light-yellow reaction mixture is stirred at room temperature for 2 hours. After about 1.5 hour observed precipitation. The mixture is then poured into 1M aqueous HCl (300 ml) and the white solid is separated by filtration, washed with water (200 ml) and dried in high vacuum. This interim phthalimide (4,40 g) is suspended in ethanol and added dropwise hydrazine monohydrate (0,62 g). The mixture is heated to boiling under reflux and stirred for 4 hours. The mixture is cooled to room temperature and removed by filtering the solid. The filtrate is evaporated under reduced pressure and the residue re-suspended in diethyl ether (200 ml). Add 4M HCl in dioxane (3,075 ml) and saducees substance separated by filtration, get mentioned in the title compound as a white solid.13C-NMR (DMSO-d6) δ 145,7, 140,1, 139,2, 105,5, 62,7, 62,2.

Obtaining 19:

Hydrochloride, O-(4-bromobenzyl)hydroxylamine

Synthesized as described for obtaining 18, from 4-bromobenzylamine and N-hydroxyphthalimide.13C-NMR (DMSO-d6) δ133,1, 131,5, 131,3, 122,3, 74,7.

20:

Hydrochloride, O-(2-iodine-benzyl)hydroxylamine

Synthesized according to the procedure described in obtaining 18, from 2-identilied (Aldrich) and N-hydroxyphthalimide. Reacting 2-identilied and N-hydroxyphthalimide obtaining intermediate phthalimide is 20 hours.

Getting 21:

Hydrochloride, O-(3-jobensis)hydroxylamine

Synthesized according to the procedure described in obtaining 18, based on 3-jodensavanne (Lancaster) and N-hydroxyphthalimide.13C-NMR (DMSO-d6) δ 137,5, 137,4, 136,2, 130,7, 128,4, 94,8, 74,5.

Obtaining 22:

(2-Aminoacetonitrile)acetonitrile

To a stirred solution of 2-methylbenzylamine (3,11 ml) in CCl4(100 ml) is added N-bromosuccinimide (4,89 g) and a catalytic amount of benzoyl peroxide. The mixture is heated at boiling under reflux and stirred for 1.5 hours. Cool the mixture to room temperature and filtered. The filtrate is evaporated under reduced pressure and the residue is dissolved in minimum amount of EtOAc and add petroleum ether. The obtained solid substance was separated by filtration and washed with petroleum ether, receive (2-bromomethylphenyl)acetonitrile (926 mg). The filtrate is evaporated the ri reduced pressure and the residue chromatographic on silica gel (elution with a mixture petroleum ether/EtOAc 10/1, about./vol.), receiving an additional quantity (2-bromomethylphenyl)acetonitrile (1.45 g). This benzylbromide of 2.27 g) dissolved in NMP and add N-hydroxyphthalimide (1,53 g), and then one drop of 1,8-diazabicyclo[5,4,0]undec-7-ene (1,40 ml). The reaction mixture was stirred at room temperature for 5 hours. Add 1M aqueous HCl (173 ml) and the resulting saducees substance separated by filtration, washed with water and dried in a high vacuum, receive [2-(1,3-dioxo-1,3-dihydroindol-2-intoximeter)phenyl]acetonitrile (2.25 g). This interim phthalimide (2,23 g) is dissolved in dichloromethane and add methylhydrazine (1.1 EQ.). The reaction mixture was stirred at room temperature for 30 min and the resulting solid removed by filtration. The filtrate is evaporated under reduced pressure and the residue chromatographic on a column of silica gel (a mixture of petroleum ether/EtOAc 3/1, vol./vol.), get listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 135,0, 130,9, 129,7, 129,2, 129,2, 128,3, 118,0, 75,8, 21,1.

23:

O-(2-Benzensulfonamidelor)hydroxylamine

Get analogously to the method described for obtaining 15, based on N-hydroxyphthalimide and 1-(methyl bromide)-2-[(phenylsulfonyl)methyl]benzene (Aldrich).13C-NMR (DMSO-d6) δ 138,6, 137,5, 133,8, 132,3, 130,8, 129,0, 128,6, 128,4, 127,4, 75,6, 59,3.

Obtaining 24:

(4-Aminoantipyrine)metalgearsolid

Get the method similar to that described to obtain 18 on the basis of N-hydroxyphthalimide and 4-(chloromethyl)benzyl alcohol (Aldrich).13C-NMR (DMSO-d6) δ 143,6, 131,8, 129,0, 126,4, 75,5, 62,4.

Obtaining 25:

Hydrochloride, O-(4-fluoro-2-trifloromethyl)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 4-fluoro-2-(trifluoromethyl)benzylbromide (Matrix).13C-NMR (DMSO-d6) δ 161,8, 135,0, 128,0, 122,9, 119,8, 114,0, 71,0.

Receiving 26:

Hydrochloride, O-(2-fluoro-6-trifloromethyl)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 2-fluoro-6-(trifluoromethyl)benzylbromide (Aldrich).13C-NMR (DMSO-d6) δ 161,9, 132,8, 130,3, 123,1, 122,4, 120,4, 118,6, 65,2.

Receive 27:

Hydrochloride, O-(4-fluoro-3-trifloromethyl)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 4-fluoro-3-(trifluoromethyl)benzylbromide (Matrix).13C-NMR (DMSO-d6) δ 159,1, 136,3, 131,2, 128,2, 122,4, 117,5, 116,7, 73,9.

Receive 28:

O-(4-Methyl-3-trifloromethyl)hydroxylamine

Get the method similar to that described to obtain 15 on the basis of N-hydroxyphthalimide and 4-methyl-3-(trifluoromethyl)benzylbromide (JRD Fluorochemicals).13C-NMR (DMSO-d6) δ 136,4, 135,5, 132,1, 131,5, 129,0, 125,8, 124,5, 77,0, 19,1.

Receiving 29:

Hydrochloride, O-(4-methoxy-3-trifloromethyl)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 4-methoxy-3-(trifluoromethyl)benzylbromide (Fluorochem).13C-NMR (DMSO-d6) δ 157,5, 135,6, 128,0, 125,7, 123,4, 116,8, 113,0, 74,5, 56,3.

30:

Hydrochloride, O-(2-Methoxybenzyl)hydroxylamine

Get the method similar to that described to obtain 18 on the basis of N-hydroxyphthalimide and 2-methoxybenzylamine (Aldrich).13C-NMR (DMSO-d6) δ 157,5, 130,8, 130,7, 121,5, 120,3, 111,1, 70,8, 55,4.

Getting 31:

O-(4-Interoceanic)hydroxylamine

To a stirred solution of N-hydroxyphthalimide (2,45 g), 4-interoceanico alcohol (Aldrich, of 2.92 g) and triphenylphosphine (4,72 g) in THF was added drop diethylazodicarboxylate (1.2 EQ.). The reaction mixture was stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the residue chromatographic on a column of silica gel (a mixture of petroleum the ether/EtOAc, 1/2, vol./about.) and get 2-(4-interoceanica)isoindole-1,3-dione. This interim phthalimide (4.35 g) was dissolved in dichloromethane and add methylhydrazine (1.1 EQ.). The reaction mixture was stirred at room temperature for 60 min and the resulting solid removed by filtration. The filtrate is evaporated under reduced pressure and the residue chromatographic on a column of silica gel (a mixture of petroleum ether/EtOAc, 5/1, vol./vol.), get listed in the title compound (2.55 g).13C-NMR (DMSO-d6) δ 159,1, 130,1, 129,2, 114,5, 77,7, 68,0, 29,0, 28,2, 22,5, 14,0.

Obtaining 32:

Hydrochloride, O-(2-cryptomaterial)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 2-(triptoreline)benzylbromide (Matrix).13C-NMR (DMSO-d6) δ 146,9, 132,0, 131,3, 127,7, 126,3, 120,7, 120,0, 69,7.

Receive 33:

Hydrochloride, O-(3-cryptomaterial)hydroxylamine

Get the method similar to that described to obtain 18 on the basis of N-hydroxyphthalimide and 3-(triptoreline)benzylbromide (Yarsley).13C-NMR (DMSO-d6) δ 148,3, 136,5, 130,6, 128,0, 121,4, 121,3, 120,0, 74,5.

Receive 34:

Hydrochloride, O-(4-cryptomaterial)hydroxylamine

Get method, and is similar to that described for obtaining 18, on the basis of N-hydroxyphthalimide and 4-(triptoreline)benzylbromide (Aldrich).13C-NMR (DMSO-d6) δ 148,7, 133,2, 131,2, 121,1, 120,0, 74,5.

Receive 35:

Hydrochloride, O-(2-deformational)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 2-(deformedarse)benzylbromide (Matrix).13C-NMR

(DMSO-d6) δ 149,4, 131,5, 130,9, 125,4, 124,7, 118,3, 116,4, 70,1.

Receive 36:

Hydrochloride, O-(2-triftormetilfullerenov)hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and 2-(triptoreline)benzylbromide (Matrix).13C-NMR (DMSO-d6) δ 138,6, 137,9, 132,1, 131,4, 130,5, 123,3, 73,1.

Receive 37:

Hydrochloride, O-(6-chlorobenzo[1,3]dioxol-5-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 18 on the basis of N-hydroxyphthalimide and 6-chloropiperonyl (Aldrich).13C-NMR (DMSO-d6) δ 148,9, 146,5, 126,2, 124,2, 111,1, 109,8, 102,3, 72,7.

Obtaining 38:

O-Benzo[1,3]dioxol-5-almatygidrogeologiya

Get the method similar to that described to obtain 15 on the basis of N-hydroxyphthalimide and 3,4-methylenedioxyaniline (Fluorochem).13C-I Is R (DMSO-d 6) δ 147,5, 147,2, 131,0, 121,9, 108,7, 107,9, 100,8, 77,5.

Obtaining 39:

Hydrochloride O-indan-5-almatygidrogeologiya

Get the method similar to that described to obtain 31, on the basis of N-hydroxyphthalimide and 5-hydroxyethylidene (Tyger). Salt is hydrochloride receive, adding 4M HCl in dioxane (1.0 EQ.) to initially received hydroxylamine.13C-NMR (DMSO-d6) δ 144,8, 144,1, 131,3, 127,4, 125,3, 124,2, 75,8, 32,0, 24,9.

Obtaining 40:

3-Aminoacetonitrile

Get the method similar to that described to obtain 15 on the basis of N-hydroxyphthalimide and 3-bromomethylbiphenyl.13C-NMR (DMSO-d6) δ 139,5, 132,5, 131,7, 131,5, 129,2, 118,7, 112,6, 76,5.

Getting 41:

2-Aminoacetonitrile

Get the method similar to that described to obtain 15 on the basis of N-hydroxyphthalimide and 2-bromomethylbiphenyl.13C-NMR (DMSO-d6) δ 141,3, 132,9, 132,8, 129,5, 128,4, 117,5, 112,4, 75,3.

Obtaining 42:

Hydrochloride 4-aminoacetyl-3-perbenzoate

Get the method similar to that described to obtain 22, from 3-fluoro-4-methylbenzonitrile (Apollo).13C-NMR (DMSO-d6) δ 160,0, 132,6, 128,9, 126,9, 119,5, 117,3, 113,5, 68,7.

Receive 43:

Hydrochloride 4-aminoach imethyl-2-bromobenzonitrile

Get the method similar to that described to obtain 22, from 2-bromo-4-methylbenzonitrile (Chemie Brunschwig).13C-NMR (DMSO-d6) δ 141,5, 135,0, 132,8, 128,3, 124,4, 116,9, 114,4, 73,7.

Receiving 44:

Hydrochloride 4-aminoacetyl-3-chlorobenzonitrile

Get the method similar to that described to obtain 22, from 3-chloro-4-methylbenzonitrile (Aldrich).13C-NMR (DMSO-d6) δ 137,3, 133,7, 132,8, 131,4, 131,4, 117,2, 113,1, 72,0.

45:

Hydrochloride 4-aminoacetyl-3-methoxybenzonitrile

Get the method similar to that described to obtain 22, from 3-methoxy-4-methylbenzonitrile (Apin).13C-NMR (DMSO-d6) δ 157,2, 130,7, 127,5, 124,5, 118,4, 114,4, 112,7, 69,9, 56,2.

Receive 46:

Hydrochloride 4-aminoacetyl-3-idententical

Get the method similar to that described to obtain 22, on the basis of 3-iodine-4-methylbenzonitrile.13C-NMR (DMSO-d6) δ 141,9, 132,1, 129,9, 116,9, 113,0, 99,3, 78,1.

Getting 47:

3-Aminoacetyl-4-bromobenzonitrile

Get the method similar to that described to obtain 22, from 4-bromo-3-methylbenzonitrile (Lancaster).

Receive 48:

Hydrochloride 4-aminoacylation-carbonitrile

Get the method similar to that described to obtain 22, from 1-cyano-4-methylnaphthalene (Aldrich).13C-NMR (DMSO-d6) δ 135,6, 132,8, 131,6, 131,1, 129,1, 128,3, 128,0, 125,3, 124,8, 117,2, 110,5, 73,0.

Getting 49:

Hydrochloride, O-(4-Morpholine-4-ylbenzyl)hydroxylamine

Get the method similar to that described to obtain 31, on the basis of (4-morpholinomethyl)methanol (Maybridge) and N-hydroxyphthalimide. Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.

Obtaining 50:

Hydrochloride, O-(2-Morpholine-4-ylbenzyl)hydroxylamine

Get the method similar to that described to obtain 31, on the basis of (2-morpholinoethyl)methanol (Maybridge) and N-hydroxyphthalimide. Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.1H-NMR (DMSO-d6) δ 11,3 (s, 3H), 7,45-7,35 (m, 2H), 7,25 to 7.1 (m, 2H), 5,19 (s, 2H), 3,79 (m, 4H); is 2.88 (m, 4H).

Getting 51:

O-(2-Aminobenzyl)hydroxylamine

Get the method similar to that described to obtain 31, from 2-aminobenzamide alcohol and N-hydroxyphthalimide.13C-NMR (CDCl3) δ 146,4, 131,2, 129,7, 121,4, 118,1, 115,9, 76,6./p>

Getting 52:

Hydrochloride methyl ester 3-aminooxyacetic acid

Methyl 3-(methyl bromide)benzoate (Lancaster, 5.0 g), tert-butyl-n-hydroxycarbonate (4.35 g) was dissolved in acetonitrile (40 ml). Add potassium carbonate (3.77 g) and the mixture is stirred at room temperature for 3 hours. The mixture is diluted with EtOAc and washed with water and saturated salt solution. The organic layer is dried (MgSO4) and the mixture is filtered through a layer of silica gel, rinsing EtOAc (100 ml). The combined filtrates evaporated under reduced pressure. The remaining oil is dissolved in EtOAc (40 ml) and added 4M HCl in dioxane (5.5 ml)and then water (0.4 ml). The mixture is stirred at room temperature for 3 hours and the resulting solid is separated by filtration and dried in high vacuum, getting listed at the beginning of the connection.

13C-NMR (DMSO-d6) δ 165,8, 134,5, 133,8, 129,9, 129,6, 129,1, 74,9, 52,2.

Getting 53:

O-Naphthalene-1-almatygidrogeologiya

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and 1-chloromethylation.13C-NMR (DMSO-d6) δ 133,5, 133,2, 131,4, 128,2, 126,8, 126,7, 126,0, 125,6, 125,2, 124,1, 75,4. 5

Getting 54:

Hydrochloride, O-(1-phenylethyl)hydroxylamine

Get p is the method similar to that described to obtain 18. The initial substance: N-hydroxyphthalimide and 1-fenilatilamin (Aldrich).13C-NMR (DMSO-d6) δ 138,9, 128,7, 128,6, 126,8, 81,4, 20,6.

Receive 55:

Hydrochloride O-[1-(2-triptoreline)ethyl]hydroxylamine

Get the method similar to that described to obtain 13 on the basis of N-hydroxyphthalimide and alpha-methyl-2-(trifluoromethyl)benzylbromide (Matrix).13C-NMR (DMSO-d6) δ 138,5, 133,3, 129,0, 127,5, 126,1, 125,6, 124,0, 77,1, 21,9.

Getting 56:

Hydrochloride On-pyridine-2-almatygidrogeologiya

Get the method similar to that described to obtain 12, based on N-hydroxyphthalimide 2-chloromethylpyridine.

Getting 57:

Hydrochloride, O-(2,6-dichloropyridine-4-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 18. The initial substance: N-hydroxyphthalimide and 4-methyl bromide-2,6-dichloropyridine (Maybridge).1H-NMR (DMSO-d6) δ 11,2 (user.,3H), a 7.62 (s, 2H), by 5.18 (s, 2H).

Getting 58:

Hydrochloride O-thiazole-4-almatygidrogeologiya

Get the method similar to that described to obtain 18. The initial substance: N-hydroxyphthalimide and 4-(chloromethyl)thiazolidinone (TCl).13C-NMR (DMSO-d6) δ 155, 1mm, 149,2, 1214, 70,3.

Getting 59:

O-(2-Chlorothiazole-5-ylmethyl)hydroxylamine

2-[(2-Chloro-1,3-thiazol-5-yl)methoxy]-1H-isoindole-1,3(2H)-dione (Bionet, 5.0 g), suspended in ethanol (120 ml) and added hydrazine monohydrate (0,83 ml). The mixture is heated to boiling under reflux and stirred at this temperature for 4 hours. The mixture is cooled to room temperature and removed by filtering the solid. The filtrate is evaporated under reduced pressure. The residue re-suspended in diethyl ether (400 ml) and added 4M HCl in dioxane (4,25 ml). The solid is separated by filtration and dried in vacuum, get mentioned in the title compound (3.3 g).13C-NMR (DMSO-d6) δ 152,5, 143,3, 133,5, 66,9.

Getting 60:

Hydrochloride, O-(2-phenylthiazol-4-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 12 on the basis of N-hydroxyphthalimide and 4-chloromethyl-2-phenyldiethanolamine.

Getting 61:

O-(5-Methylisoxazol-3-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 15. The initial substance: N-hydroxyphthalimide and 3-chloromethyl-5-methylisoxazole (Maybridge).13C-NMR (DMSO-d6) δ 169,1, 161,5, 101,4, 68,0, 11,7.

Getting 62:

Hydrochloride, O-(3-Dimethylisoxazol-4-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and 4-(chloromethyl)for 3,5-dimethylisoxazol (Aldrich).13C-NMR (DMSO-d6) δ 169,7, 159,6, 108,2, 64,4, 10,8, 9,5.

Getting 63:

O-(3-Propylenoxide-5-ylmethyl)hydroxylamine

Step 1: to a stirred solution of N-hydroxyphthalimide (50.5 g) and propargylamine (37,0 g) in DMF (250 ml) at 0°C was added drop triethylamine (50 ml). Remove the cooling bath and the reaction mixture was stirred at room temperature for 4 hours. The mixture is then poured into ice water and separated saducees substance by filtration. The crude product is recrystallized from ethanol and receive 2-prop-2-ynyloxy-isoindole-1,3-dione (47,5 g). Stage 2: intermediate obtained above phthalimide (1 mmol) is mixed with steam-trilinoleate (2.8 mmol), triethylamine (0.05 mmol) and 1-nitrobutane (1.44 mmol) in toluene (3 ml). The reaction mixture was stirred at room temperature for 48 hours, filtered and chromatographic on a column of silica, receiving 2-(3-propylenoxide-5-ylethoxy)isoindole-1,3-dione. Stage 3: the above cycloaddition product was dissolved in a mixture of methanol + dichloromethane and added dropwise hydrazine monohydrate (1 EQ.). The reaction mixture was stirred at room t is mperature for 20 hours and leave at 5°C for 3 hours. The solid is removed by filtration and the filtrate is evaporated under reduced pressure and get listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 169,0, 163,2, 103,0, 67,4, 27,2, 21,0, 13,5.

Getting 64:

O-(5-chlorothiophene-2-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 15. The initial substance: N-hydroxyphthalimide and 2-chloro-5-(chloromethyl)thiophene (Aidrich).13C-NMR (DMSO-d6) δ 140,2, 127,9, 126,3, 126,0, 71,1.

Getting 65:

4-(2-Aminoacetyl)benzonitrile

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 4-(2-hydroxyethyl)benzonitrile (Maybridge).13C-NMR (DMSO-d6) δ 145,6, 131,9, 129,9, 118,9, 108,7, 74,6, 34,3.

Getting 66:

Hydrochloride O-cyclopentanetetracarboxylic

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and (hydroxymethyl)cyclopentane (Aidrich). Instead of diethylazodicarboxylate use diisopropylsalicylic and formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.13C-NMR (DMSO-d6) δ 77,9, 37,1, 28,8, 24,9.

Getting 67:

Hydrochloride O-cyclopropa is methylhydroxylamine

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and bromelicola.13C-NMR (DMSO-d6) δ 78,4, 8,5, 3,0.

Getting 68:

Hydrochloride, O-(2,2-dimethylpropyl)hydroxylamine

Get the method similar to that described to obtain 66. The initial substance: N-hydroxyphthalimide and 2,2-dimethyl-1-propanol.13C-NMR (DMSO-d6) δ 82,9, 31,2, 26,1.

Getting 69:

Hydrochloride, O-(2-ethylbutyl)hydroxylamine

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and 1-bromo-2-ethylbutane.13C-NMR (DMSO-d6) δ 66,3, 39,2, 22,6, 10,7.

Getting 70:

Hydrochloride, O-(3-methylbutyl)hydroxylamine

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and isoamylase.13C-NMR (DMSO-d6) δ 72,5, 35,8, 24,4, 22,3.

Getting 71:

Hydrochloride O-cyclobutanedicarboxylate

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and cyclobutylamine (Aldrich).13C-NMR (DMSO-d6) δ 77,6, 32,3, 24,1, 18,0.

The floor is giving 72:

Hydrochloride O-cyclohexyldimethylamine

Get the method similar to that described to obtain 13. The initial substance: N-hydroxyphthalimide and cyclohexylethylamine.13C-NMR (DMSO-d6) δ 78,8, 35,7, 28,8, 25,7, 24,9.

Getting 73:

Hydrochloride O-cyclohexylethylamine

Methanol (20 ml) cooled to 0°C and add acetylchloride (2.0 ml). The mixture is stirred for 10 min and add cycloheptanone acid (2.0 ml). The cooling bath is removed and the mixture is heated to boiling under reflux and stirred for 8 hours. Cool the mixture to room temperature and the solvent is evaporated under reduced pressure. The residue is extracted with EtOAc. The organic layer was washed with saturated aqueous sodium bicarbonate, dried (Na2SO4) and evaporated under reduced pressure, obtaining the methyl ester cycloheptanone acid (1,82 g) as a pale yellow liquid. This intermediate methyl ester (1.8 g) is dissolved in THF (25 ml) and cooled to -40°C. was Added drop sociallyengaged (11.5 ml 1,0M solution in THF). The reaction mixture is allowed to slowly warm to 0°C and continue stirring at this temperature for 3 hours. Add aqueous sodium hydroxide (5 ml of 1M solution) and the mixture of the filter is so The filtrate is evaporated under reduced pressure and re-dissolved in EtOAc (20 ml), dried (Na2SO4) and evaporated under reduced pressure, get cycloheptylmethyl (1,37 g) as a clear colorless oil. This intermediate alcohol in turn specified in the title compound, as described to obtain 66, using N-hydroxyphthalimide.13C-NMR (DMSO-d6) δ 78,8, 37,1, 30,0, 27,9, 25,6.

Getting 74:

O-Cyclooctylmethyl

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and cyclooctanone (Acros).13C-NMR (DMSO-d6) δ 82,3, 36,4, 29,4, 27,0, 26,5, 25,5.

Getting 75:

Hydrochloride, O-(1-cyclopentylmethyl)hydroxylamine

Get the method similar to that described to obtain 66. The initial substance: N-hydroxyphthalimide and 1-cyclopentylamine (Aldrich).13C-NMR (DMSO-d6) δ 83,8, 43,4, 28,3, 28,1, 25,0, 25,0, 16,9.

Getting 76:

Hydrochloride O-cyclohexylhydroxylamine

Get the method similar to that described to obtain 15. The initial substance: N-hydroxyphthalimide and cyclohexylamine (Fluka).13C-NMR (DMSO-d6) δ 81,2, 29,8, 24,6, 22,7.

Getting 77:

Hydrochloride, O-(2-cyclopropylethyl)hydroxyl is mine

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 2-cyclopropylethanol (Lancaster). Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.). getting the corresponding hydrochloride salt.13C-NMR (DMSO-d6) δ 74,2, 31,9, 7,2, 4,0.

Getting 78:

O-(2-Cyclopentylmethyl)hydroxylamine

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 2-cyclopentylamine (Lancaster).13C-NMR (CDCl3) δ 75,7, 37,0, 34,6, 32,8, 25,1.

Getting 79:

O-(3-Cyclopentylpropionyl)hydroxylamine

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 3-cyclopentyl-1-propanol (Aldrich).13C-NMR (CDCl3) δ 76,5, 40,0, 32,7, 32,4, 27,7, 25,2.

80:

Hydrochloride O-cyclohex-3-Energeticheskaya

Get the method similar to that described to obtain 66. The initial substance: N-hydroxyphthalimide and 1,2,3,6-tetrahydrobenzoic alcohol (Aldrich).13C-NMR (DMSO-d6) δ 126,9, 125,4, 78,1, 31,8, 27,4, 24,5, 23,7.

Getting 81:

Hydrochloride, O-(6-methylcyclohex-3-animetal)hydroxylamine

Get the method similar to that described to obtain 66. The initial substance: N-hydroxyphthalimide and 6-methyl-3-cyclohexen-1-methanol (Aldrich). The final product contains some impurities, but is used without additional purification.

Getting 82:

(TRANS-4-aminoacetanilide)methanol

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and TRANS-1,4-cyclohexanedimethanol (Acros).13C-NMR (CDCl3) δ 81,6, 68,2, 40,3, 36,8, 29,0, 28,7.

Getting 83:

Hydrochloride, O-(3-methoxycyclohexyl)hydroxylamine

Get the method similar to that described to obtain 73, based on 3-methoxycyclohexanone acid (Aldrich). Specified in the header of the connection does not get in its pure form, but is used without additional purification.

Getting 84:

Hydrochloride O-adamantane-1-almatygidrogeologiya

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 1-adamantanemethanol (Aldrich). Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.13C-NMR (DMSO-d6) δ 83,2, 38,5, 36,3, 25 33,2, 27,2.

Getting 85:

Hydrochloride O-bicyclo[2.1.1]hept-2-almatygidrogeologiya

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and 2-hydroxymethyluracil[2.2.1]heptane (Aldrich). Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.13C-NMR (DMSO-d6) δ 77,1, 75,7, 39,1, 37,7, 37,5, 37,2, 35,8, 35,4, 34,9, 33,3, 32,9, 29,1, 28,9, 28,2, 22,2.

Getting 86:

Hydrochloride, O-(6,6-dimethylbicyclo[3,1,1]hept-2-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 31. The initial substance: N-hydroxyphthalimide and (1S,2R)-10-penarol (Fluka). Formed first free hydroxylamine treated with 4M HCl in dioxane (1.0 EQ.), getting the corresponding hydrochloride salt.13C-NMR (DMSO-d6) δ 78,3, 42,4, 40,5, 38,6, 37,9, 32,0, 27,5, 25,3, 22,8, 17,9.

Getting 87:

Hydrochloride, O-(tetrahydrofuran-2-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 18. The initial substance: N-hydroxyphthalimide and tetrahydrofurfuryl bromide.1H-NMR (DMSO-d6) δ 11,08 (s,3H), 4,1 to-3.9 (m,3H), 3,8 - 3,6 (m, 2H), of 2.0 to 1.7 (m,3H), 1,6 of-1.45 (m, 1H).

Getting 88:

Hydrochloride, O-(tetrahydrofuran-3-ylmethyl)hydroxylamine

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Get the method similar to that described to obtain 66. The initial substance: N-hydroxyphthalimide and (tetrahydrofuran-3-yl)methanol (Aldrich),13C-NMR (DMSO-d6) δ 75,6, 69,3, 66,7, 36,7, 28,1.

Getting 89:

O-(3-Methyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine

N-Hydroxyphthalimide (48,9 g) dissolved in DMF (200 ml) and add triethylamine (43,9 ml), and then allylbromide. The reaction mixture was stirred at room temperature for 18 h and the resulting saducees substance is removed by filtration. The filtrate is concentrated under reduced pressure. The residue is dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate, 4M aqueous HCl and saturated salt solution. The organic layer is dried (MgSO4) and evaporated under reduced pressure. The remaining substance is crystallized from a mixture of hexane/EtOAc, receiving 2-allyloxymethyl-1,3-dione (43,6 g). This intermediate allyl (2,03 g) dissolved in toluene (5 ml) and added nitroethane (825 mg), phenylisocyanate (2.4 ml) and triethylamine (0.02 EQ.). The reaction mixture was stirred at room temperature for 48 hours and saducees substance is removed by filtration. The filtrate is evaporated onto silica gel and chromatographic (from 0 to 50% EtOAc/heptane)will receive 2-(3-methyl-4,5-dihydroisoxazole-5-ylethoxy)isoindole-1,3-dione (2.4 g).13C-NMR (DMSO-d ) δ 162,9, 155,4, 134,7, 128,5, 123,2, 78,0, 76,9, 40,3, 12,4. This interim phthalimide (260 mg) was dissolved in methanol (1 ml) and added dichloromethane (1 ml) and hydrazine monohydrate (1.0 EQ.). The mixture is stirred at room temperature for 20 hours. The resulting solid is removed by filtration. The filtrate is evaporated under reduced pressure and get listed in the title compound which is used without further purification.

Getting 90:

O-(3-Ethyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 89, using 1-nitropropane instead of nitroethane.13C-NMR (DMSO-d6) δ 159,5, 76,9, 76,3, 38,7, 20,5, 10,6.

Getting 91:

O-(3-Butyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 89, using 1-nitropentane instead of nitroethane.13C-NMR (DMSO-d6) δ 158,5, 76,8, 76,3, 38,8, 27,8, 26,5, 21,6, 13,5.

Getting 92:

Hydrochloride, O-(tetrahydropyran-4-ylmethyl)hydroxylamine

Methyl tetrahydropyran-4-carboxylate (Fluka) reduced to the corresponding alcohol sociallyengaged and in turn specified in the title compound, as described to obtain 73.13C-NMR (DMSO-d6) the 78,1, 66,3, 33,0, 28,7.

Getting 93:

Hydrochloride, O-(tetrahydropyran-2-ylmethyl)hydroxylamine

Get the method similar to that described to obtain 18. The initial substance: N-hydroxyphthalimide and 2-(methyl bromide)tetrahydro-2H-Piran (Aldrich).13C-NMR (DMSO-d6) δ 76,6, 74,5, 67,1, 26,9, 25,2, 22,3.

Getting 94-170:

These compounds get the method similar to that described above for 8-93. Determined that13C-NMR data are fully consistent with their structures.

Example 1:

N-Benzyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 1)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 166,9, 149,7, 149,1, 148,3, 136,1, 132,5, 129,0, 128,4, 128,3, 128,2, 122,1, 114,9, 113,6, 111,6, 76,9, 44,9.

Example 2:

N-(4-Nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 2)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(4-nitrobenzyl)hydroxylamine (Aldrich).

1H-NMR (DMSO-d6) δ of 11.69 (users, 1H), 8,49 (d, 2H), compared to 8.26 (d, 2H), 7,89 (users, 1H), to 7.77 (d, 2H), 7,38 (d, 1H), 7,30 (m, 2H), 7,20 (m, 1H), 6,55 (t, 1H), 6,51 (d, 1H), 5,1 (, 2H), 4,46 (d, 1H).

Example 3:

N-(2-Nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 3)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(2-nitrobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,5, 149,5, 148,9, 148,3, 147,8, 133,7, 132,6, 131,6, 130,4, 129,3, 128,1, 124,6, 122,0, 114,8, 113,0, 111,5, 73,2, 44,8.

Example 4:

2-[(Pyridine-4-ylmethyl)amino]-N-(3-triftormetilfosfinov)benzamide (compound 4}

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-trifloromethyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,0, 148,3, 137,5, 132,7, 132,6, 129,3, 129,0, 128,0, 125,1, 124,8, 124,1, 122,0, 114,8, 113,3, 111,5, 76,0, 44,8.

Example 5:

2-[(Pyridine-4-ylmethyl)amino]-N-(2-triftormetilfosfinov)benzamide (compound 5)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(2-trifloromethyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,5, 149,5, 149,0, 148,3, 134,3, 132,6, 132,5, 131,1, 128,7, 128,1, 126,9, 125,6, 124,2, 122,0, 114,8, 113,1, 111,5, 72,7, 44,8.

Example 6:

N2-[(N is ridin-4-ylmethyl)amino]-N-(4-triftormetilfosfinov)benzamide (compound 6)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(4-trifloromethyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,4, 149,6, 149,0, 148,3, 140,9, 132,6, 129,2, 128,6, 128,1, 125,1, 124,2, 122,0, 114,8, 113,2, 111,5, 76,0, 44,8.

Example 7:

N-(4-Methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 7)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-methoxybenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,1, 159,3, 149,5, 149,0, 148,3, 132,4, 130,6, 128,0, 127,8, 122,0, 114,8, 113,6, 113,5, 111,4, 76,6, 55,0, 44,8.

Example 8:

N-(3-Methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 8)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(3-methoxybenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,1, 159,1, 149,5, 149,0, 148,3, 137,5, 132,4, 129,3, 128,0, 122,0, 120,8, 114,8, 114,0, 113,7, 113,4, 111,4, 76,7, 54,9, 44,8.

Example 9:

2-[(Pyridine-4-ylmethyl)amino]-N-(3,4,5-trimethoxybenzoate)benzamide (compound 9)

General method 1, pic is b 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3,4,5-trimethoxybenzyl)hydroxylamine (see getting 8).13C-NMR (DMSO-d6) δ 167,1, 152,7, 149,5, 149,0, 148,2, 137,3, 132,5, 131,6, 128,1, 121,9, 114,8, 113,5, 111,4, 105,9, 76,9, 59,9, 55,8, 44,8

Example 10:

N-(4-Chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl-amino]benzamide (compound 10)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(4-Chlorobenzyl)hydroxylamine (see 9).

13C-NMR (DMSO-d6) δ 167,2, 149,5, 149,0, 148,3, 135,0, 132,8, 132,5, 130,7, 128,2, 128,0, 122,0, 114,8, 113,3, 111,5, 76,0, 44,8.

Example 11:

N-(3-Chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 11)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(3-Chlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,8, 149,5, 149,0, 148,3, 138,6, 132,9, 132,5, 130,1, 128,4, 128,1, 127,2, 122,0, 114,8, 113,3, 111,5, 76,0, 44,8.

Example 12:

N-(2-Chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 12)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see receipt is 1) and the hydrochloride of O-(2-Chlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,0, 148,3, 133,5, 133,1, 132,5, 131,3, 130,0, 129,2, 128,1, 127,1, 122,0, 114,8, 113,3, 111,4, 73,7, 44,8.

Example 13:

N-(2-Bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 13)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-bromobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 149,0, 148,3, 135,3, 132,5, 132,4, 131,1, 130,2, 128,2, 127,7, 123,2, 122,0, 114,8, 113,2, 111,4, 75,9, 44,8.

Example 14:

N-(2,4-Dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 14)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2,4-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,3, 134,2, 133,7, 132,8, 132,6, 128,7, 128,1, 127,3, 121,9, 114,8, 113,2, 111,4, 73,0, 44,8.

Example 15:

N-(3,4-Dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 15)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3,4-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 148,9, 148,3, 137,4, 132,6, 130,9, 130,7, 130,5, 130,4, 18,9, 128,1, 121,9, 114,8, 113,2, 111,5, 75,3, 44,8.

Example 16:

N-(2,6-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 16)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2,6-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,0, 148,3, 136,7, 132,4, 131,5, 131,3, 128,5, 128,3, 121,9, 114,7, 113,4, 111,3, 70,7, 44,8.

Example 17:

N-(3,5-Dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 17)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3,5-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9,148,3, 140,6, 133,8, 132,6, 128,0, 127,6, 127,1, 121,9, 114,8, 113,2, 111,5, 75,3, 44,8.

Example 18:

N-(2,3-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 18)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2,3-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 148,9, 148,3, 136,3, 132,6, 131,7, 131,1, 130,3, 129,7, 128,1, 128,0, 121,9, 114,8, 113,2, 111,4, 74,1, 44,8.

Example 19:

N-(2,5-Dichloraniline)-2-[(n is ridin-4-ylmethyl)amino]benzamide (compound 19)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and hydrochloride, O-(2,5-dichlorobenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,3, 135,9, 132,5, 131,7, 131,5, 130,8, 130,4, 129,6, 128,1, 121,9, 114,8, 113,1, 111,5, 73,1, 44,8.

Example 20:

N-(2-Forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 20)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,2, 160,8, 149,5, 149,0, 148,3, 132,0, 130,7, 128,1, 124,3, 122,8, 122,0, 115,4, 115,1, 114,8, 113,3, 111,4, 70,2, 44,8.

Example 21:

N-(3-Forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 21)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 162,0, 149,5, 148,9, 148,3, 138,9, 132,5, 130,2, 128,0, 124,5, 122,0, 115,3, 114,9, 114,7, 113,3, 111,5, 76,0, 44,8.

Example 22:

N-(4-Forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 22)

General procedure 1, method 1.

Source the substances: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,2, 162,0, 149,5, 149,0, 148,3, 132,5, 132,2, 131,1, 128,0, 122,0, 115,2, 114,8, 113,3, 111,5, 76,1, 44,8.

Example 23:

N-(2-Chloro-6-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 23)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-chloro-6-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 162,0, 149,5, 149,0, 148,3, 135,9, 132,4, 131,7, 128,1, 125,4, 121,9, 121,7, 114,7, 114,5, 113,3, 111,4, 66,9, 44,7.

Example 24:

N-(2-Chloro-4-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 24)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-chloro-4-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 161,8, 149,5, 149,0, 148,3, 134,3, 133,1, 132,5, 130,1, 128,1, 122,0, 116,5, 114,8, 114,3, 113,2, 111,5, 73,0, 44,8.

Example 25:

N-(3-Chloro-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 25)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-chloro-2-terbisil)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,2, 156,0, 149,5, 148,9, 148,3, 12,5, 130,9, 130,8, 128,0, 125,2, 124,9, 121,9, 119,5, 114,8, 113,2, 111,4, 70,2, 44,7.

Example 26:

Methyl ester of 4-{2-[(Pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 26)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of the methyl ester of 4-aminooxyacetic acid (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,3, 166,0, 149,5, 148,9, 148,3, 141,5, 132,5, 129,3, 129,1, 128,7, 128,1, 122,0, 114,8, 113,2, 111,5, 76,2, 52,1, 44,8.

Example 27:

N-(4-Cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 27)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,4, 149,6, 148,9, 148,3, 141,8, 132,6, 132,2, 129,1, 128,1, 122,0, 118,7, 114,8, 113,1, 111,5, 110,8, 75,9, 44,8.

Example 28:

2-[(Pyridine-4-ylmethyl)amino]-N-(quinoline-2-ylethoxy)benzamide (compound 28)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-quinoline-2-almatygidrogeologiya (see 11).

13C-NMR (DMSO-d6) δ 156,9, 149,5, 148,9, 148,2, 146,8, 136,6, 132,5, 129,6, 128,6, 128,1, 127,8, 127,3, 126,6, 121,9, 120,, 114,8, 113,2, 111,4, 78,3, 44,8.

Example 29:

N-Phenoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 29)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-phenylhydroxylamine (Fluka).

13C-NMR (DMSO-d6) δ 159,7, 149,6, 148,8, 148,6, 133,1, 129,4, 128,3, 122,2, 122,0, 114,9, 112,9, 112,1, 111,7, 44,8.

Example 30:

N-(2-Phenoxyethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 30)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-phenoxyethyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 167,5, 158,5, 149,8, 149,2, 148,6, 132,8, 129,6, 128,3, 122,2, 120,8, 115,0, 114,6, 113,4, 111,7, 74,0, 65,7, 45,0.

Example 31:

N-(3-Phenylpropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 31)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-phenylpropyl)hydroxylamine (SPECS).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,3, 141,6, 132,4, 128,3, 128,2, 128,0, 125,7, 122,0, 114,8, 113,5, 111,5, 74,5, 44,8, 31,4, 29,6.

Example 32:

N-(2-Methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 32)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 167,1, 165,3, 150,5, 149,5, 148,9, 148,3, 132,5, 128,1, 122,0, 119,0, 114,8, 113,4, 111,4, 71,9, 55,9, 44,8, 18,6.

Example 33:

N-benzyloxy-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 33)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 156,7, 151,2, 149,7, 149,4, 136,2, 136,0, 129,0, 128,3, 122,1, 111,2, 108,4, 77,0, 42,8.

Example 34:

2-(4-Forbindelsen)-N-(4-methoxybenzyloxy)nicotinamide (compound 34)

General procedure 1, method 1.

The initial substance: 2-(4-forbindelsen)nicotinic acid (see 3) and the hydrochloride of O-(4-methoxybenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 165,7, 161,0, 159,3, 156,7, 151,2, 136,4, 136,0, 130,6, 129,1, 127,8, 114,9, 113,6, 113,5, 110,8, 108,0, 76,6, 55,0, 43,0.

Example 35:

2-(4-Methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 35)

General procedure 1, method 1.

The initial substance: 2-(4-methoxybenzylamine)nicotinic acid (see the doctrine 4) hydrochloride and O-(4-methoxybenzyl)hydroxylamine (Bionet research intermediates).

13C-NMR (DMSO-d6) δ 165,8, 159,3, 158,1, 156,8, 151,2, 135,9, 131,9, 130,6, 128,6, 127,7, 113,7, 113,6, 110,6, 107,7, 76,6, 55,0, 54,9, 43,3.

Example 351:

N-(4-Cianfrocca)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 36)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and 4-aminoacetonitrile (obtained using the techniques described in the work Petrassi, H.M. and other Organic Letters, 2001, 3, 139-142)

13C-NMR (DMSO-d6) δ 165,5, 154,0, 150,8, 149,6, 148,4, 135,8, 133,9, 131,8, 123,6, 121,9, 118,3, 115,2, 112,1, 108,6, 108,1, 44,6.

Example 352:

N-(4-Bromophenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 37)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-bromophenyl)hydroxylamine (obtained using the techniques described in the work Petrassi, H.M. and other Organic Letters, 2001, 3, 139-142).

13C-NMR (DMSO-d6) δ 165,9, 150,7, 149,7, 149,6, 148,4, 135,6, 132,2, 131,8, 124,5, 121,9, 118,0, 115,2, 112,0, 108,4, 44,6.

Example 353:

N-(4-Fluoro-2,6-dimethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 38)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(4-fluoro-2,6-dimethylbenzimidazole (see 13)

13C-NMR (DMSO-d6) δ 167,3, 161,6 (d), 149,5, 149,0, 148,4, 141,6 (d), 132,5, 128,3(d), 128,0, 121,9, 114,8, 114,0(d), 113,3, 111,5, 70,4, 44,7, 19,2.

Example 354:

N-(4-Fluoro-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 39)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(4-fluoro-2-methoxybenzyl)hydroxylamine (see getting 14).

13C-NMR (DMSO-d6) δ 167,1, 163,2 (d), 158,9 (d), 149,5, 149,0, 148,3, 132,4, 132,0(d), 128,1, 122,0, 120,1, 114,8, 113,5, 111,4, 106,2 (d), 99,3 (d), 71,0, 55,9, 44,8.

Example 355:

N-(2,3-Debtor-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 40)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(2,3-debtor-4-methylbenzyl)hydroxylamine (see getting 15).13C-NMR (CDCl3) δ 169,2, 149,7, 149,6 (DD), 149,1 (DD), 149,1, 148,7, 133,5, 128,1 (d), uniforms, 127.6, 125,7 (m), 121,9, 115,7, 112,7, 112,0, 71,3, 46,0, 14,4.

Example 356:

N-(3-Fluoro-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 41)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-fluoro-4-methylbenzyl)hydroxylamine (see getting 16)

13C-NMR (who MCO-d 6) δ 167,3, 160,5 (d), 149,5, 149,3, 148,4, 136,1 (d), to 132.6, 131, 5mm (d), 128,2, of 124.6 (d), of 124.1 (d), 122,1, or 115.1 (d), 114,9, 113,5, 111,6, 76,1, 44,9, 14,0.

Example 357:

N-(5-fluoro-2-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 42)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(5-fluoro-2-methylbenzyl)hydroxylamine (see getting 17).

13C-NMR (DMSO-d6) δ 167,3, 160,2 (d), 149,5, 149,0, 148,3, 136,2 (d), 133,2 (d), 132,5, 131, 5mm (d), 128,1, 121,9, 116,1 (d), 114,8, to 114.7 (d), 113,3, 111,5, 74,5, 44,8, 17,7.

Example 358:

2-[(Pyridine-4-ylmethyl)amino]-N-(2,3,5,6-titrator-4-methoxybenzyloxy)benzamide (compound 43)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(2,3,5,6-titrator-4-methoxybenzyl)hydroxylamine (see getting 18).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,0, 148,3, 145,8 (m), 139,9 (m), 138,4 (m), 132,6, 128,0, 121,9, 114,8, 113,1, 111,5, 107,8 (t), 63,4, 62,2 (t), 44,7.

Example 359:

N-(4-Bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 44)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-bromobenzyl)hydroxylamine (see getting 19).

13NMR (DMSO-d 6) δ 167,2, 149,5, 148,9, 148,3, 135,4, 132,5, 131,1, 130,9, 128,0, 121,9, 121,4, 114,8, 113,3, 111,5, 76,0, 44,7.

Example 360:

N-(2-Jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 45)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-jobensis)hydroxylamine (see 20)

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,3, 138,9, 138,4, 132,5, 130,2, 130,1, 128,2, 128,2, 121,9, 114,8, 113,2, 111,4, 99,3, 80,2, 44,7.

Example 361:

N-(3-Jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 46)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-jobensis)hydroxylamine (see getting 21)

13C-NMR (DMSO-d6) δ 166,9, 149,5, 148,9, 148,1, 138,7, 137,1, 136,8, 132,4, 130,4, 128,0, 121,9, 114,8, 113,2, 111,4, 94,6, 75,8, 44,7

Example 362:

N-(4-Methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 47)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-methylbenzyl)hydroxylamine (Bionet)

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,3, 137,5, 132,9, 132,4, 128,9, 128,8, 128,0, 122,0, 114,8, 113,5, 111,4, 76,7, 44,8, 20,7.

Example 363:

N-[2-(3,3-D is methylbut-1-enyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 48)

Through a mixture of N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (example 360, 151 mg, 0.33 mmol) in toluene (20 ml) was bubbled argon for 10-15 minutes Add tetrakis(triphenylphosphine)palladium (19 mg) and the mixture stirred for 10 min before adding 3,3-dimethyl-1-butylboronic acid (Aldrich, 50 mg) and degassed solution of 2M sodium carbonate (0,329 ml). The reaction flask (spiral tube) sealed and the reaction mixture is heated to 120°C for 3 hours. Add tetrakis(triphenylphosphine)palladium (of 0.05 equiv.) 2M sodium carbonate (0,329 ml) and 3,3-dimethyl-1-butylboronic acid (50 mg) and continue stirring at 120°C during the night. The mixture is cooled to room temperature, add 25% ammonium acetate and continue stirring for 10 minutes the Mixture was partitioned between EtOAc and water. The aqueous phase is extracted with EtOAc and the combined organic layers washed with a saturated solution of salt, dried (MgSO4) and evaporated under reduced pressure. The remainder chromatographic on silica gel (elution with 1% methanol in dichloromethane.about.) and get listed in the title compound (130 mg).13C-NMR (CDCl3) δ 168,9, 149,8, 149,1, 148,7, 145,1, 138,8, 133,4, 131,1, 129,2, 127,4, 126,8, 126.2, 122,0, 121,5, 115,7, 112,8, 112,0, 76,2, 46,1, 33,8, 29,6.

Example 364:

2-[(Pyridine-4-ylmethyl)amino]-N-(2-streventname)benzamide (connect the tion 49)

The technique is similar to that described for an example 363.

Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (example 360) and TRANS-2-venividibatna acid (Aldrich).

13C-NMR (CDCl3) δ 151,2, 148,7, 148,0, 138,1, 137,3, 133,4, 132,5, 131,5, 129,5, 128,6, 127,9, 127,7, 127,6, 126,9, 125,9, 125,5, 122,4, 116,0, 112,7, 111,9, 76,4, 46,1.

Example 365:

N-[3-(3-Hydroxyprop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 50)

N-(3-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (example 361, 300 mg), propargilovyh alcohol (69 mg), CuI (19 mg), PdCl2(PPh3)2(22 mg) and tetrabutylammonium (241 mg) was dissolved in DMF (4 ml) and added drop by drop the triethylamine (0.5 ml) (exothermic reaction). The reaction mixture was stirred at room temperature for 30 min and partitioned between EtOAc and water. The aqueous phase is extracted with EtOAc and the combined organic layers washed with a saturated solution of salt, dried (MgSO4) and evaporated under reduced pressure. The residue is purified by chromatography on silica gel (EtOAc as eluent) and receive specified in the header of the connection.

13C-NMR (DMSO-d6) δ 167,2, 149,5, 148,9, 148,3, 136,6, 132,5, 131,5, 130,9, 128,7, 128,6, 128,0, 122,3, 114,8, 113,3, 111,5, 90,0, 83,3, 76,3, 49,3, 44,8.

Example 366:

N-[3-(5-CANopen-1-inyl)benzyloxy]-2-[(pyridine-4-ileti is)amino]benzamide (compound 51)

Use a technique similar to that described for an example 365, but without adding tetrabutylammonium. Source materials: N-(3-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 361) and 5-cyano-1-Pentin (Aldrich).

13C-NMR (DMSO-d6) δ 167,2, 149,5, 148,9, 148,3, 136,4, 132,5, 131,6, 131,0, 128,6, 128,5, 128,0, 122,8, 120,1, 114,8, 113,3, 111,5, 88,7, 81,2, 76,3, 44,8, 24,0, 17,8, 15,5

Example 367:

N-[2-(3-Hydroxy-prop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 52)

Use a technique similar to that described for an example 365, but without adding tetrabutylammonium. Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 360) and propargilovyh alcohol.

13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,0, 148,3, 137,4, 132,5, 131,7, 129,0, 128,4, 128,2, 122,0, 121,8, 114,8, 113,2, 111,4, 94,2, 81,0, 74,6, 49,4, 44,7.

Example 368:

2-[3-(2-{2-[(Pyridine-4-ylmethyl)amino]benzylaminocarbonyl}phenyl)prop-2-ynyloxy]

ethyl ester of acetic acid (compound 53)

Use a technique similar to that described for an example 365, but without adding tetrabutylammonium. Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 360) and 2-(prop-2-ynyloxy)in ethyl acetate (Maybridge).

13 C-NMR (DMSO-d6) δ 170,2, 167,3, 149,5, 148,9, 148,3, 137,6, 132,5, 131,9, 129,4, 128,7, 128,3, 128,1, 121,9, 121,5, 114,8, 113,3, 111,4, 90,0, 83,4, 74,6, 67,1, 62,9, 58,0, 44,8, 20,5.

Example 369:

N-[2-(3-Methyl-3H-imidazol-4-ylethynyl)benzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 54)

Use a technique similar to that described for an example 365, but without adding tetrabutylammonium. Specified in the title compound purified by crystallization from ethanol.

Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 360) and 5-ethinyl-1-methyl-1-H-imidazole (Aldrich).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 148,9, 148,2, 139,5, 137,0, 134,0, 132,5, 131,5, 129,8, 128,8, 128,5, 128,1, 121,9, 121,8, 115,0, 114,8, 113,4, 111,4, 93,5, 81,8, 74,7, 44,8, 31,7.

Example 370:

N-[3-(3-Methyl-3H-imidazol-4-ylethynyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 55)

Use a technique similar to that described for an example 365, but without adding tetrabutylammonium. Specified in the title compound purified by crystallization from ethanol.

Source materials: N-(3-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 361) and 5-ethinyl-1-methyl-1-H-imidazole (Aldrich).

13C-NMR (DMSO-d6) δ 167,2, 149,5, 148,9, 148,2, 139,5, 136,8, 133,9, 132,5, 131,2, 130,7, 129,2, 128,7, 128,0, 121,9, 121,8, 114,8, 113,3, 111,5, 95,5, 77,8, 76,2, 44,8, 31,6.

Example 371/u>

N-(2-Cyanomethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 56)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and (2-aminoacetonitrile)acetonitrile (see getting 22).

13C-NMR (CDCl3) δ 169,5, 149,8, 149,2, 148,8, 133,7, 132,9, 131,7, 131,0, 130,1, 129,4, 128,3, 127,5, 122,0, 118,3, 115,7, 112,3, 112,2, 76,5, 46,0, 21,2.

Example 372:

N-(2-Benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide 10 (compound 57)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(2-benzensulfonamidelor)hydroxylamine (see 23)

13C-NMR (CDCl3) δ 168,6, 149,5, 148,9, 148,5, 138,7, 135,2, 133,6, 133,1, 132,3, 131,6, 129,1, 128,8, 128,2, 127,7, 127,3, 121,7, 115,5, 112,3, 111,7, 76,1, 58,8, 45,7.

Example 373:

N-(4-Hydroxymethylbenzene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 58)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and (4-aminoantipyrine)methanol hydrochloride (see getting 24)

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,3, 142,6, 134,1, 132,4, 128,7, 128,0, 126,2, 122,0, 114,8, 113,5, 111,4, 76,8, 62,6, 44,8.

Example 374:

N-(4-fluoro-2-trifluoromethyl what ensilage)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 59)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-(4-fluoro-2-trifloromethyl)hydroxylamine (see getting 25).

13C-NMR (DMSO-d6) δ 167,4, 161,3 (d), 149,5, 148,9, 148,3, 134,2 (d), to 132.6, 130,7, 129,1 (m), 128,1, of 123.2 (m), 121,9, 119,4 (d), 114,8, to 113.4 (m), 113,0, 111,5, 72,1, 44,8.

Example 375:

N-(2-Fluoro-6-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 60)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-fluoro-6-trifloromethyl)hydroxylamine (see getting 26).

13C-NMR (DMSO-d6) δ of 167.2, 162,2 (d), 149,5, 149,0, 148,3, 132,4, 131,7 (d), 130,3 25 (m), 128,1, 123,4 (m), 121,9, 121,4, 120,1 (d), 114,7, 113,1, 111,4, 66,1, 44,7.

Example 376:

N-(4-Fluoro-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 61)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-fluoro-3-trifloromethyl)hydroxylamine (see getting 27).

13C-NMR (DMSO-d6) δ 167,4, 158,7 (d), 149,6, 149,0, 148,4, 135,7 (d), 133,5 (d), 132,7, 128,1, 127,6, 122,6 (kV), 122,0, 117,2 (d)116,5 (m), 114,9, 113,3, 111,6, 75,4, 44,9.

Example 377:

N-(4-Methyl-3-t is attorneyinsurance)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 62)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-methyl-3-trifloromethyl)hydroxylamine (see getting 28)

13C-NMR (CDCl3) δ 169,3, 149,6, 149,1, 148,8, 137,2, 133,5, 132,4, 132,2, 129,1 (kV), uniforms, 127.6, 126,6 (kV), to 124.4 (kV), 122,0, 115,6, 112,7, 112,0, 77,5, 46,0, 19,1.

Example 378:

N-(4-Methoxy-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 63)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(4-methoxy-3-trifloromethyl)hydroxylamine (see getting 29).

13C-NMR (DMSO-d6) δ 167,2, 157,0, 149,5, 149,0, 148,2, 135,0, 132,5, 128,0, 127,5 (kV), 123,6 (kV)121,9, 116,6 (kV), 114,8, 113,4, 112,6, 111,4, 75,7, 56,1, 44,8.

Example 379:

N-(2-Methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 64)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-methoxybenzyl)hydroxylamine (see 30)

13C-NMR (DMSO-d6) δ 167,1, 157,2, 149,5, 149,0, 148,3, 132,4, 130,4, 129,7, 128,1, 123,8, 121,9, 120,0, 114,8, 113,5, 111,4, 110,8, 71,5, 55,3, 44,8.

Example 380:

N-(4-Interoceanica)-2-[(pyridine-4-ylmethyl)amino]benzamide (connect the tion 65)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(4-interoceanic)hydroxylamine (see getting 31).

13C-NMR (CDCl3) δ 168,8, 159,7, 149,7, 149,0, 148,8, 133,3, 131,0, 127,5, 127,3, 122,0, 115,7, 114,6, 113,0, 112,0, 78,1, 68,1, 46,0, 28,9, 28,2, 22,5, 14,0.

Example 381:

2-[(Pyridine-4-ylmethyl)amino]-N-(2-cryptomaterial)benzamide (compound 66)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-cryptomaterial)hydroxylamine (see getting 32)

13C-NMR (DMSO-d6) δ 167,5, 149,6, 149,0, 148,5, 146,8, 132,7, 131,8, 130,4, 128,7, 128,2, 127,5, 122,0, 120,6, 120,2 (kV), 114,9, 113,3, 111,6, 70,8, 44,9.

Example 382:

2-[(Pyridine-4-ylmethyl)amino]-N-(3-cryptomaterial)-benzamide (compound 67)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-cryptomaterial)hydroxylamine (see getting 33).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 148,9, 148,3, 138,9, 132,6, 130,2, 128,0, 127,6, 121,9, 120,8, 120,6, 120,0 (kV), 114,8, 113,2, 111,5, 75,9, 44,8.

Example 383:

2-[(Pyridine-4-ylmethyl)amino]-N-(4-cryptomaterial)benzamide (compound 68)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-cryptomaterial)hydroxylamine (see getting 34).

13C-NMR (DMSO-d6) δ 167,3, 149,6, 149,0, 148,3, 148,2, 135,6, 132,5, 130,7, 128,1, 122,0, 120,8, 120,0 (kV), 114,8, 113,3, 111,5, 75,9, 44,8.

Example 384:

N-(2-Differentoccasions)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 69)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-deformational)hydroxylamine (see getting 35).

13C-NMR (DMSO-d6) δ 167,4, 149,6, 149,1, 148,4, 132,6, 131,6, 130,2, 128,2, 127,4, 125,4, 122,0, 119,1, 116,9 (t), 114,9, 113,4, 111,5, 71,4, 44,9.

Example 385:

2-[(Pyridine-4-ylmethyl)amino]-N-(2-triftormetilfullerenov)benzamide (compound 70)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-triftormetilfullerenov)hydroxylamine (see getting 36).

13C-NMR (DMSO-d6) δ 167,3, 149,5, 148,9, 148,3, 140,8, 137,4, 132,6, 131,6, 131,3, 129,7, 129,5 (kV), 128,1, 123,2, 121,9, 114,8, 113,2, 111,5, 74,5, 44,8.

Example 386:

N-(6-Chlorobenzo[1,3]dioxol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 71)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(6-chlorobenzo[1,3]dioxol-5-ylmethyl)hydroxylamine (see getting 37)

13C-NMR (DMSO-d6) δ 167,2, 149,5, 149,0, 148,2, 148,1, 146,4, 132,4, 128,1, 126,8, 125,3, 121,9, 114,8, 113,3, 111,4, 110,6, 109,4, 102,1, 73,5, 44,8.

Example 387:

N-(Benzo[1,thioxo-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 72)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-benzo[1,3]dioxol-5-almatygidrogeologiya (see getting 38)

13C-NMR (DMSO-d6) δ 166,8, 149,7, 149,6, 149,1, 148,3, 147,3, 147,2, 132,5, 129,9, 128,1, 122,9, 122,1, 122,0, 114,9, 113,6, 111,5, 109,4, 108,0, 101,0, 76,7, 44,9.

Example 388:

N-(Indan-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 73)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-indan-5-almatygidrogeologiya (see getting 39).

13C-NMR (DMSO-d6) δ 167,2, 150,1, 149,0, 148,3, 143,9, 143,8, 133,7, 132,5, 128,2, 127,1, 125,1, 124,0, 122,3, 115,0, 113,7, 111,5, 77,2, 44,9, 32,2, 32,1, 25,1.

Example 389:

N-(3-Cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 74)

A General method is ka 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and 3-aminoacetonitrile (see getting 40).

13C-NMR (CDCl3) δ 169,6, 150,3, 149,7, 149,2, 148,8, 137,2, 133,8, 133,3, 132,4, 132,3, 129,5, 127,4, 122,7, 122,0, 118,5, 115,8, 112,8, 112,2, 46,0.

Example 390:

N-(2-Cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 75)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see receipt of 1) and 2-aminoacetonitrile (see getting 41).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 148,9, 148,2, 139,3, 133,1, 132,8, 132,4, 130,7, 129,2, 128,1, 121,9, 117,2, 114,7, 113,1, 111,9, 111,4, 74,2, 44,7.

Example 391:

N-(4-Cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 76)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacetyl-3-perbenzoate (see getting 42).

13C-NMR (DMSO-d6) δ 167,3, 160,1 (d), 149,5, 148,9, 148,2, 132,7, 132,6 (d), to 129.2 (d), of 128.6 (d), 128,1, 121,9, 119,2 (d)117,5 (d), 114,8, level 113.0, 112,7 (d), 111,4, 69,7, 44,7.

Example 392:

N-(3-Bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 77)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ileti is)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacetyl-2-bromobenzonitrile (see getting 43)

13C-NMR (DMSO-d6) δ 149,5, 148,9, 148,2, 144,2, 134,7, 132,6, 132,3, 128,0, 127,9, 15 124,2, 121,9, 117,1, 114,8, 113,7, 113,0, 111,5, 75,2, 44,7.

Example 393:

N-(2-chloro-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 78)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacetyl-3-chlorobenzonitrile (see getting 44).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,2, 139,6, 133,5, 132,5, 131,3, 131,0, 128,1, 121,9, 117,3, 114,8, 112,9, 112,4, 111,5, 73,1, 44,7.

Example 394:

N-(4-Cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 79)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 167,2, 157,1, 154,5, 148,0, 145,9, 132,6, 130,3, 130,0, 128,2, 124,4, 123,2, 118,6, 115,1, 114,1, 113,4, 111,7, 111,4, 71,0, 56,0, 45,0.

Example 395:

N-(4-Cyano-2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 80)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacetyl-3-idententical (see getting 46).

13C-NMR (VHI is-d 6) δ 167,4, 149,5, 148,9, 148,3, 144,3, 141,7, 132,6, 131,9, 129,7, 128,2, 121,9, 117,0, 114,8, 112,9, 112,3, 111,5, 98,8, 79,7, 44,8.

Example 396:

N-(2-Bromo-5-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 81)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and 3-aminoacetyl-4-bromobenzonitrile (see getting 47).

13C-NMR (DMSO-d6) δ 167,5, 149,5, 148,9, 148,3, 137,4, 133,8, 133,2, 132,7, 128,7, 128,1, 121,9, 118,0, 114,8, 113,0, 111,5, 110,7, 75,2, 44,8.

Example 397:

N-(4-Cyanonaphthalene-1 ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 82)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and 4-aminoacylation-1-carbonitrile (see getting 48).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 149,0, 148,3, 138,0, 132,7, 132,6, 131,6, 131,3, 15 128,9, 128,1, 128,0, 127,1, 125,9, 124,6, 121,9, 117,4, 114,8, 113,1, 111,5, 109,7, 74,4, 44,8.

Example 398:

N-(4-(Morpholine-4-ivasilaki)-2-[(pyridine-4-ylmethyl)-amino]benzamide (compound 83)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(4-morpholine-4-ylbenzyl)hydroxylamine (see getting 49).

13C-NMR (DMSO-d6) δ 167,0,151,0, 149,5, 149,0, 148,2, 132,4, 130,2, 128,0, 126,1, 122,0, 114,8, 114,5, 113,6, 111,4, 76,7, 66,0, 48,1, 44,8.

Example 399:

N-(2-Morpholine-4-ivasilaki)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 84)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-morpholine-4-ylbenzyl)hydroxylamine (see getting 50).

13C-NMR (DMSO-d6) δ 167,1, 151,9, 149,5, 148,9, 148,3, 132,5, 131,4, 129,7, 129,3, 128,1, 123,0, 121,9, 119,1, 114,8, 113,4, 111,5, 72,9, 66,6, 53,0, 44,8.

Example 400:

N-(2-Aminobenzoate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 85)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(2-aminobenzyl)hydroxylamine (see getting 51).

13C-NMR (CDCl3) δ 169,7, 149,8, 149,1, 148,8, 147,8, 133,7, 131,3, 130,7, 127,5, 121,9, 118,4, 117,3, 115,8, 112,3, 112,2, 77,5, 46,0.

Example 401:

N-(2-Benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 86)

To a stirred solution of N-(2-aminobenzoate)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 400) in dichloromethane at 0-5°C add triethylamine (1.2 EQ.), and then benzosulphochloride (1.1 EQ.). Mixture is allowed to warm to room temperature and stirred for 20 h is S. The solvent is evaporated under reduced pressure and the residue is dissolved in EtOAc and washed with water and saturated salt solution. The organic layer is dried (MgSO4) and evaporated under reduced pressure. The residue is purified by the method of column chromatography on silica gel (petroleum ether/EtOAc, 2/1, vol/about.) and get listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 170,7, 149,6, 149,4, 149,1, 140,7, 138,3, 134,2, 132,5, 131,0, 130,7, 128,8, 127,4, 126,9, 125,3, 124,5, 123,0, 122,2, 115,7, 112,4, 111,1, 76,6, 46,0.

Example 402:

Methyl ester of 3-{2-[(Pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 87)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of the methyl ester of 3-aminooxyacetic acid (see getting 52).13C-NMR (DMSO-d6) δ 167,2, 166,0, 149,5, 148,9, 148,3, 136,7, 133,6, 132,5, 129,6, 129,4, 128,9, 128,7, 128,0, 121,9, 114,8, 113,3, 111,5, 76,2, 52,1, 44,8.

Example 403:

3-{2-[(Pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 88)

To a stirred solution of methyl ester 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 402, 89 mg) in methanol (3 ml) is added 2M sodium hydroxide (1 ml). The reaction mixture was stirred at room temperature is re within 7 hours. The mixture was diluted with water (12 ml) and acidified with 4M aqueous HCl. Received saducees substance separated by filtration and dried in vacuum, obtaining specified in the header of the connection.13C-NMR (DMSO-d6) δ 167,2, 167,1, 149,5, 149,0, 148,3, 136,4, 133,1, 132,5, 130,8, 129,7, 129,1, 128,5, 128,0, 121,9, 114,8, 113,3, 111,4, 76,3, 44,7.

Example 404:

4-{2-[(Pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 89)

Get a manner analogous to that described for an example 403. Starting material: methyl ester of 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 26).13C-NMR (DMSO-d6) δ 167,2, 167,0, 149,5, 149,0, 148,3, 140,9, 132,5, 130,4, 129,2, 128,6, 128,0, 122,0, 114,8, 113,2, 111,5, 76,2, 44,7.

Example 405:

N-[4-(Morpholine-4-carbonyl)benzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 90)

To a stirred mixture of 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 404, 220 mg) in DMF (3 ml) is added N,N'-carbonyldiimidazole (99 mg). The mixture is stirred at room temperature for 45 min and add the hydrochloride of the research (79 mg). The reaction mixture was stirred at room temperature for 18 h and poured into water. The product is extracted with EtOAc several times and the combined organic layers washed with water and feast upon the authorized salt solution, dried (Na2SO4) and evaporated under reduced pressure. The residue is purified by the method of column chromatography on silica gel (EtOAc as eluent) and receive specified in the header of the connection.13C-NMR (DMSO-d6) δ 168,7, 167,2, 149,5, 149,0, 148,3, 137,4, 135,3, 132,5, 128,8, 128,1, 127,0, 122,0, 114,8, 113,3, 111,5, 76,4, 66,0, 44,7.

Example 406:

N-(3-(4-(3-Cyano-2-yl)piperazine-1-carbonyl]benzyloxy}-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 91)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and 2(1-piperazinil)nicotinamide (Emka-chemie).1H-NMR (DMSO-d6) δ 11,5 (users, 1H), 8,48 (m, 2H), 8,43 (DD, 1H), 8,10 (DD, 1H), 7,89 (users, 1H), 7,60-7,53 (m, 2H), 7,50 (t, 1H), 7,44 (dt, 1H), 7,38 (DD, 1H), 7,30 (m, 2H), 7,16 (m, 1H), 6,97 (DD, 1H), 6,54 (m, 1H), of 6.49 (userd, 1H), to 5.00 (s, 2H), 4,46 (d, 2H), 4,00-to 3.36 (m, 8H).

Example 407:

N-[3-(4-Methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 92)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and 1-methylpiperazine.1H-NMR (CDCl3) δ 11,6 (users, 1H), 8,49 (m, 2H), 7,92 (users, 1H), 7,55 (userd, 1H), 7,50-7,42 (m, 2H), 7,4-7,33 (m, 2H), 7,31 (m, 2H), 7,19 (users, 1H), 6,60-6,47 (m, 2H), to 4.98 (s, 2H), 4,46 (d, 2H), 3,80-3,10 (m, 4H), 2,17 (s, 3H), 2,44 is 2.00 (m, 4H).

Example 408:

N-[3-(Morpholine-4-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 93)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and the hydrochloride of the research.1H-NMR (DMSO-d6) δ 11,6 (users, 1H), 8,49 (m, 2H), 7,89 (users, 1H), 7,56 (m, 1H), 7,52-7,44 (m, 2H), 7,42-7,34 (m, 2H), 7,31 (m, 2H), 7,19 (m, 1H), 6,58-of 6.49 (m, 2H), to 4.98 (s, 2H), 4,47 (d, 2H), 3,80-3,10 (m, 8H).

Example 409:

N-[3-(3-Hydroxypyrrolidine-1-carbonyl]benzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 94)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and 3-pyrrolidine (Aldrich).1H-NMR (DMSO-d6) δ (2 rotamer) 11,64 and are 11.62 (users, 1H), 8,49 (m, 2H), 8,00-7,80 (m, 1H), to 7.61 (users, 1H), 7,56 (dt, 1H), 7,53-7,42 (m, 2H), 7,38 (userd, 1H), 7,31 (m, 2H), 7,19 (users, 1H), 6,60-6,47 (m, 2H), to 4.98 (s, 2H), 4,47 (d, 2H), 4,32, and is 4.21 (m, 1H), 3,68-3,14 (m, 5H), 2,02-of 1.62 (m, 2H).

Example 410:

N-[4-(4-Methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 95)

Paluchato method similar to that described for an example 405. Educt: 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 404) and 1-methylpiperazin. Specified in the title compound crystallized from toluene.13C-NMR (DMSO-d6) δ 168,6, 167,2, 149,5, 148,9, 148,2, 137,3, 135,7, 132,4, 128,7, 128,0, 126,8, 121,9, 114,8, 113,3, 111,4, 76,4, 54,4, 46,8, 45,5, 44,8.

Example 411:

N-[3-(2-Dimethylaminoethanol)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 96)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and 2-diethylaminoethylamine.13C-NMR (DMSO-d6) δ 165,8, 149,5, 148,9, 148,2, 136,1, 134,6, 132,4, 131,4, 128,2, 128,0, 127,7, 126,8, 121,9, 114,8, 113,3, 111,4, 76,5, 58,1, 45,2, 44,8, 37,3.

Example 412:

N-[3-(2-Pyrrolidin-1-iletileri)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 97)

Get the method similar to that described for an example 405. Educt: 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (see example 403) and N-(2-amino-ethyl)pyrrolidine (Aldrich).

13C-NMR (DMSO-d6) δ 166,8, 165,8, 149,5, 148,9, 148,2, 136,1, 134,5, 132,4, 131,4, 128,2, 128,0, 127,7, 126,9, 121,9, 114,8, 113,3, 111,4, 76,5, 54,8, 53,6, 44,8, 38,5, 23,0.

Example 413:

<> 2-[(Pyridine-4-ylmethyl)amino]-N-(2-thiophene-2-ivasilaki)benzamide (compound 98)

Get the method similar to that described for an example 363. Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 360) and thiophene-2-baronova acid (Aldrich).

1H-NMR (DMSO-d6) δ 11,60 (users, 1H), 8,49 (m, 2H), of 7.90 (users, 1H), 7,71 to 7.62 (m, 2H), 7,52-7,37 (m, 5H), 7,31 (m, 2H), 7.23 percent-to 7.15 (m, 2H), 6,60-6,47 (m, 2H), 4,99 (s, 2H), 4,46 (users, 2H).

Example 414:

N-(4'-Methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 99)

Get the method similar to that described for an example 363. Source materials: N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (see example 360 4-methoxyphenylalanine acid (Aldrich).

13C-NMR (CDCl3) δ 168,8, 159,0, 149,7, 149,1, 148,8, 142,8, 133,5, 132,8, 132,6, 131,0, 130,5, 130,4, 128,8, 127,3, 127,3, 122,0, 115,6, 113,7, 112,7, 112,1, 76,5, 55,3, 46,0.

Example 415:

N-(Naphthalene-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 100)

Pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C, 150 mg) and O-naphthalene-1-almatygidrogeologiya (getting 53, of 1.05 equiv.) dissolved in DMF and stir the mixture heated to 50°C. the Reaction mixture is stirred at this temperature in ECENA 15 an hour. The mixture is cooled to room temperature and partitioned between EtOAc and water. The organic layer was washed with a saturated solution of salt, dried (MgSO4) and evaporated under reduced pressure. The residue is purified by the method of column chromatography on silica gel (petroleum ether/EtOAc) and receive specified in the header of the connection.13C-NMR (DMSO-d6) δ 167,3, 149,5, 149,1, 148,4, 133,2, 132,5, 131,9, 131,4, 129,3, 128,4, 128,2, 126,3, 126,1, 125,9, 125,2, 124,8, 121,9, 114,8, 113,4, 111,5, 75,3, 44,8.

Example 416:

N-(1-Phenylethane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 101)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(1-phenylethyl)hydroxylamine (see getting 54).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,0, 141,5, 132,3, 128,1, 127,8, 126,7, 122,0, 114,7, 113,8, 111,3, 81,6, 44,7, 20,8.

Example 417:

2-[(Pyridine-4-ylmethyl)amino]-N-[1-(2-triptoreline)ethoxy]benzamide (compound 102)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-[1-(2-triptoreline)ethyl]hydroxylamine (see getting 55).

13C-NMR (DMSO-d6) δ 167,5, 149,6, 149,0, 148,2, 141,4, 132,9, 132,5, 128,3, 128,2, 128,1, 126,1, 125,0, 124,2, 122,1, 114,8, 113,5, 111,4, 77,1, 44,8, 22,0.

Example 418:

N-(Piri is in 2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 103)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-pyridine-2-almatygidrogeologiya (see getting 56)

13C-NMR (DMSO-d6) δ 167,3, 155,8, 149,5, 148,9, 148,3, 136,6, 132,5, 128,1, 123,1, 122,7, 121,9, 114,8, 113,3, 111,5, 77,8, 44,8.

Example 419:

N-(2,6-Dichloropyridine-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 104)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2,6-dichloropyridine-4-ylmethyl)hydroxylamine (see getting 57).

13C-NMR (DMSO-d6) δ 167,6, 153,2, 149,5, 149,1, 148,9, 148,3, 132,8, 128,1, 122,1, 121,9, 114,8, 112,8, 111,6, 74,1, 44,7.

Example 420:

2-[(Pyridine-4-ylmethyl)amino]-N-(thiazole-4-ylethoxy)benzamide (compound 105)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-thiazole-4-almatygidrogeologiya (see getting 58).

13C-NMR (DMSO-d6) δ 167,1, 154.2, 151,8, 149,5, 148,9, 148,2, 132,5, 128,1, 122,0, 119,4, 114,8, 113,4, 111,4, 71,8, 44,8.

Example 421:

N-(2-Chlorothiazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 106)

General method 1, sposob.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-chlorothiazole-5-ylmethyl)hydroxylamine (see getting 59).

13C-NMR (DMSO-d6) δ 167,6, 151,4, 149,5, 149,0, 148,3, 142,0, 135,9, 132,7, 128,1, 122,0, 114,8, 113,0, 111,5, 68,2, 44,7.

Example 422:

N-(2-Phenylthiazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 107)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-phenylthiazol-4-ylmethyl)hydroxylamine (see getting 60).

13C-NMR (DMSO-d6) δ 167,0, 152,1, 149,5, 148,9, 148,3, 132,9, 132,5, 130,2, 129,2, 128,2, 126,0, 121,9, 119,9, 114,8, 113,3, 111,4, 71,9, 44,8

Example 423:

N-(5-Methylisoxazol-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 108)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(5-methylisoxazol-3-ylmethyl)hydroxylamine (see getting 61).

13C-NMR (DMSO-d6) δ 169,8, 167,5, 159,7, 149,7, 149,0, 148,5, 132,8, 128,3, 122,1, 114,9, 113,2, 111,6, 102,0, 67,9, 44,9, 11,8.

Example 424:

N-(3,5-Dimethylisoxazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 109)

General procedure 1,method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3,5-dimethylisoxazol-4-ylmethyl)hydroxylamine (see getting 62).

13C-NMR (DMSO-d6) δ 168,6, 159,8, 149,5, 149,0, 148,3, 132,5, 128,0, 121,9, 114,8, 113,2, 111,5, 109,7, 65,0, 44,7, 10,5, 9,5.

Example 425:

N-(3-Propylenoxide-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 110)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(3-propylenoxide-5-ylmethyl)hydroxylamine (see getting 63).13C-NMR (DMSO-d6) δ 167,4, 166,6, 163,4, 149,5, 148,9, 148,4, 132,7, 128,1, 121,9, 114,8, 113,0, 111,5, 104,8, 66,7, 44,8, 27,1, 20,9, 13,4.

Example 426:

N-(5-Chlorothiophene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 111)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(5-chlorothiophene-2-ylmethyl)hydroxylamine (see getting 64).

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,4, 137,4, 132,6, 129,3, 128,5, 128,1, 126,4, 122,0, 114,8, 113,2, 111,5, 70,8, 44,8.

Example 427:

N-[2-(4-Cyanophenyl)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 112)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and 4-(2-aminoacetyl)benzonitrile (see getting 65).

13C-NMR (DMSO-d6) δ 167,2, 149,5, 148,9, 148,3, 144,8, 132,5, 132,0, 129,9, 128,1, 121,9, 118,9, 114,8, 113,3, 111,5, 109,0, 74,8, 44,8, 34,0.

Example 428:

N-Cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 113)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and hydrochloride O-cyclopentanecarboxylate (see getting 66).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,4, 79,4, 44,8, 37,6, 28,9, 24,9.

Example 429:

N-Cyclopropylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 114)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-cyclopropanemethylamine (see getting 67).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,3, 128,0, 122,0, 114,8, 113,6, 111,4, 79,6, 44,8, 9,2, 2,9.

Example 430:

N-Methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 115)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1)hydrochloride and O-methylhydroxylamine.

13C-NMR (DMSO-d6) δ 166,7, 149,5, 148,9, 148,3, 132,5, 128,0, 121,9, 114,8, 113,2, 20 111,5, 63,1, 44,8.

Example 431:

N-(2,2-DIMETHYLPROPANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 116)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(2,2-dimethylpropyl)hydroxylamine (see getting 68).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,3, 128,0, 121,9, 114,8, 113,5, 5 111,4, 84,9, 44,7, 31,4, 26,5.

Example 432:

N-(2-Ethylbutane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 117)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-ethylbutyl)hydroxylamine (see getting 69).

13C-NMR (DMSO-d6) δ 167,0, 149,6, 149,1, 148,4, 132,5, 128,1, 122,1, 114,9, 113,7, 111,5, 77,5, 44,9, 39,7, 22,9, 11,0.

Example 433:

N-(3-Methylbutoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 118)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(3-methylbutyl)hydroxylamine (see getting 70).13C-NMR (DMSO-d6) δ 167,1, 149,6, 149,1, 148,4, 132,5, 128,1, 122,1, 114,9, 113,6, 111,6, 73,7, 44,9, 36,6, 24,6, 22,5.

Example 434:

N-Cyclobutylmethyl and-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 119)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-cyclobutanedicarboxylate (see getting 71).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,4, 79,2, 44,8, 33,3, 24,5, 18,2.

Example 435:

N-Cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 120)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-cyclohexyldimethylamine (see getting 72).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,3, 128,0, 122,0, 114,8, 113,5, 15 111,4, 80,6, 44,8, 36,2, 29,2, 26,0, 25,2.

Example 436:

N-Cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 121)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and hydrochloride O-cyclohexylethylamine (see getting 73).

13C-NMR (DMSO-d6) δ 166,9, 149,7, 149,5, 149,0, 132,3, 128,0, 122,7, 122,0, 114,8, 111,4, 80,5, 44,9, 37,7, 30,4, 28,0, 25,9.

Example 437:

N-Cyclooctylmethyl-2-[(pyridine-4-ylmethylamino]benzamide (compound 122)

General method 1, method 2.

Source materials: 2-[(PI is one-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-cyclooctatetraene (see getting 74).

13C-NMR (CDCl3) δ 169,0, 149,7, 149,1, 148,8, 133,4, 127,3, 122,0, 115,6, 112,8, 112,1, 82,9, 46,0, 36,5, 29,3, 26,9, 26,4, 25,4.

Example 438:

N-(l-Cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 123)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(1-cyclopentylmethyl)hydroxylamine (see getting 75).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,1, 148,2, 132,2, 128,2, 122,0, 114,8, 114,0, 111,4, 84,0, 44,8, 43,9, 28,5, 28,4, 25,2, 17,3.

Example 439:

N-Cyclohexyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 124)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and hydrochloride O-cyclohexylhydroxylamine (see getting 76).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,2, 132,3, 128,1, 122,0, 114,8, 113,8, 111,4, 81,4, 44,8, 30,3, 25,1, 23,0.

Example 440:

N-(2-Cyclopropylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 125)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(2-cyclopropylethyl)hydroxylamine (see getting 77).13C-NMR (DMSO-d6) δ 167,1, 149,6, 149,1, 148,4, 132,5, 128,1, 122,1, 114,9, 113,6, 111,5, 75,3, 44,9, 32,7, 7,7, 4,2.

Example 441/u>

N-(2-Cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 126)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(2-cyclopentylmethyl)hydroxylamine (see getting 78).

13C-NMR (CDCl3) δ 169,1, 149,8, 149,1, 148,7, 133,4, 127,3, 122,0, 115,7, 112,8, 112,1, 46,0, 36,8, 34,3, 32,7, 25,1.

Example 442:

N-(3-Cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 127)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(3-cyclopentylpropionyl)hydroxylamine (see getting 79).

13C-NMR (CDCl3) δ 168,8, 149,4, 148,7, 133,0, 127,3, 121,8, 115,4, 112,7, 111,7, 77,0, 45,8, 39,7, 32,4, 31,9, 27,2, 24,9.

Example 443:

N-(Cyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 128)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-cyclohex-3-Energeticheskaya (see 80).

13C-NMR (DMSO-d6) δ 167,0, 149,4, 149,1, 148,3, 132,4, 128,0, 126,7, 125,7, 122,0, 114,8, 113,5, 111,5, 79,7, 44,8, 32,1, 27,7, 24,8, 23,8.

Example 444:

N-(6-Methylcyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 129)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(6-methylcyclohex-3-animetal)hydroxylamine (see getting 81).

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,0, 148,3, 132,4, 128,0, 125,8, 125,7, 122,0, 114,8, 113,5, 111,5, 77,8, 44,8, 38,0, 32,6, 29,2, 27,4, 19,2.

Example 445:

N-(TRANS-4-hydroxymethylglycinate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 130)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and (TRANS-4-aminoacetanilide)methanol (see getting 82).

13C-NMR (CDCl3) δ 169,1, 149,7, 149,7, 148,9, 133,4, 127,6, 122,1, 115,6, 112,9, 112,0, 82,3, 68,4, 46,0, 40,5, 37,1, 29,2, 28,8.

Example 446:

N-(3-Methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 131)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(3-methoxycyclohexyl)hydroxylamine (see getting 83).

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,4, 80,1, 78,1, 54,8, 44,8, 35,1, 34,9, 31,7, 28,5, 23,0.

Example 447:

N-(Adamantane-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 132)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-adamantane-1-almatygidrogeologiya (see getting 84).

13C-NMR (DMSO-d6) δ 166,8, 149,5, 149,0, 148,3, 132,3, 128,0, 122,0, 114,8, 113,6, 111,4, 85,4, 44,7, 36,5, 33,4, 27,4, 27,3.

Example 448:

N-(Bicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 133)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) hydrochloride and O-bicyclo[2.2.1]hept-2-almatygidrogeologiya (see getting 85).

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,4, 148,4, 132,5, 128,1, 122,1, 114,9, 113,7, 111,6, 79,1, 77,3, 44,9, 39,4, 38,1, 38,0, 37,9, 36,1, 35,6, 35,0, 33,8, 33,5, 29,4, 28,5, 22,5.

Example 449:

N-(6,6-Dimethylbicyclo[3.1.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide) (compound 134)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethyl)hydroxylamine (see getting 86).

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 25 111,5, 80,1, 44,8, 42,7, 39,3, 38,0, 32,3, 27,6, 25,5, 23,0, 18,3.

Example 450:

2-[(Pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-2-ylethoxy)benzamide (compound 135)

p>

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(tetrahydrofuran-2-ylmethyl)hydroxylamine (see getting 87).

1H-NMR (DMSO-d6) δ 11,58 (s, 1H), 8,49 (d, 2H), 7,92 (t, 1H), 7,42 (d, 1H), 7,32 (d, 2H), 7,19 (dt, 1H), 6,53 (m, 2H), 4,46 (d, 2H), 4.09 to (m, 1H), 3,88 (d, 2H), 3,8-3,6 (m, 2H), of 2.0 to 1.6 (m, 4H).

Example 451:

2-[(Pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-3-ylethoxy)benzamide (compound 136)

A General method 1A.

Educt: 1-pyridine-4-ylmethyl-1H-benzo[d][1,3]oxazin-2,4-dione (see obtaining 7A) and the hydrochloride of O-(tetrahydrofuran-3-ylmethyl)hydroxylamine (see getting 88).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,3, 132,5, 128,0, 121,9, 114,8, 113,3, 111,5, 77,2, 69,9, 66,7, 44,7, 37,3, 28,4.

Example 452:

N-(3-Methyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 137)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (see getting 89).

13C-NMR (DMSO-d6) δ 167,3, 155,4, 149,6, 149,1, 148,4, 132,6, 128,2, 122,1, 114,9, 113,3, 111,6, 76,9, 76,6, 44,9, 40,5, 12,6.

Example 453:

N-(3-Ethyl-4,5-dihydro oxazol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 138)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (see getting 90).13C-NMR (DMSO-d6) δ 167,2, 159,7, 149,5, 148,9, 148,3, 132,5, 128,1, 122,0, 114,8, 113,2, 111,5, 76,6, 76,4, 44,8, 38,7, 20,4, 10,6.

Example 454:

N-(3-Butyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 139)

Get a manner analogous to that described for example 415. Educt: pentafluorophenyl ester 2-[(pyridine-4-ylmethyl)amino]benzoic acid (getting 7C) and O-(3-butyl-4,5-dihydroisoxazole-5-ylmethyl)hydroxylamine (see getting 91).

13C-NMR (DMSO-d6) δ 167,1, 158,5, 149,4, 148,8, 148,2, 132,4, 128,0, 121,8, 114,7, 113,0, 111,4, 76,4, 76,3, 44,7, 38,5, 27,6, 26,3, 21,5, 13,4.

Example 455:

2-[(Pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-yloxy)benzamide (compound 140)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and O-(tetrahydro-2H-Piran-2-yl)hydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 166,8, 149,5, 148,9, 148,2, 132,4, 128,3, 122,0, 114,8, 113,5, 111,4, 100,8, 61,2, 44,8, 27,8, 24,6, 18,2.

Example 456:

2-[(Pyridine-4-ylmethyl)amino]-N-(then it is carbonated is Ropero-4-ylethoxy)benzamide (compound 141)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(tetrahydropyran-4-ylmethyl)hydroxylamine (see getting 92).

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,5, 79,9, 66,6, 44,8, 33,6, 29,2.

Example 457:

2-[(Pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 142)

General method 1, method 2.

Source materials: 2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1) and the hydrochloride of O-(tetrahydropyran-2-ylmethyl)hydroxylamine (see getting 93).

13C-NMR (DMSO-d6) δ 167,0, 149,5, 148,9, 148,3, 132,4, 128,0, 122,0, 114,8, 113,4, 111,4, 78,5, 74,7, 67,1, 44,8, 27,7, 25,4, 22,5.

Example 458:

4-Fluoro-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 143)

General procedure 1, method 1.

Educt: 4-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1A) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,3, 165,0, 150,8, 150,6, 149,6, 148,3, 130,6, 122,0, 118,9, 109,9, 101,5, 97,8, 71,8, 44,7, 18,6.

Example 459:

2-Fluoro-N-(2-methylthiazole-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 144)

General procedure 1, method 1.

The initial substance: 2-fluoro-6-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1B) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,4, 160,9, 160,0, 150,4, 149,4, 148,8, 147,9, 131,8, 121,9, 119,0, 106,8, 106,3, 102,4, 71,9, 45,0, 18,6.

Example 460:

5-fluoro-N-(2-methyl-thiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 145)

General procedure 1, method 1.

Educt: 5-fluoro-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1C), and hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,4, 154,1, 151,1, 150,5, 149,6, 148,8, 145,0, 122,0, 119,1, 114,2, 113,5, 112,6, 71,8, 45,1, 38,6, 18,6.

Example 461:

3-Methoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 146)

3-Methoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (200 mg, see obtaining 1D) dissolved in DMF (20 ml) and triethylamine (0,65 ml) 50-60°C. Add N,N,N',N'-tetramethyl-O-(benzotriazol-1-yl)uniterruptible (250 mg) and after 5 min add hydrochloride, O-(2-methylthiazole-4-ylmethyl)hydroxylamine (209 mg, see obtaining 12). The reaction mixture is heated to 90°C and stirred at this temperature for 2 hours. The mixture is cooled to room so the temperature and add water. The mixture is extracted with EtOAc several times and the combined organic layers washed with water, saturated aqueous sodium bicarbonate, water and saturated salt solution. The organic layer is dried (MgSO4) and evaporated under reduced pressure. The remaining substance is purified by the method of column chromatography on silica gel (elution from 1 to 4% methanol in EtOAc) and get listed in the title compound as a yellow oil.

13C-NMR (DMSO-d6) δ 165,3, 150,4, 150,0, 149,8, 149,3, 137,8, 122,2, 120,5, 118,8, 117,9, 114,0, 71,8, 55,7, 48,3, 18,6.

Example 462:

N-(4-Chlorobenzoyloxy)-3-methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 147)

General procedure 1, method 1.

Educt: 3-methoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1D) and the hydrochloride of O-(4-Chlorobenzyl)hydroxylamine (see 9).

13C-NMR (DMSO-d6) δ 166,6, 150,0, 149,8, 149,2, 137,8, 132,8, 131,3, 130,5, 128,3, 128,2, 122,2, 120,4, 117,9, 114,1, 75,8, 55,7, 48,3.

Example 463:

4,5-Dimethoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 148)

General procedure 1, method 1.

Educt: 4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1E) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (D IS CO-d 6) δ 165,3, 153,3, 150,6, 149,6, 149,1, 145,7, 138,7, 122,2, 118,9, 112,5, 103,0, 96,2, 72,0, 56,4, 55,2, 45,3, 18,6.

Example 464:

N-Benzyloxy-4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 149)

General procedure 1, method 1.

Educt: 4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1E) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,3, 153,3, 149,6, 149,2, 145,7, 138,7, 136,0, 128,8, 128,2, 128,1, 122,2, 112,5, 103,0, 96,2, 77,0, 56,4, 55,2, 45,2.

Example 465:

2-Methyl-N-(2-methylthiazole-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 150)

General procedure 1, method 1.

The initial substance: 2-methyl-6-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1F) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,4, 164,7, 150,7, 149,5, 149,3, 145,0, 135,4, 129,6, 121,9, 120,3, 118,9, 117,8, 108,2, 71,7, 45,0, 19,1, 18,6.

Example 466:

N-Benzyloxy-2-methyl-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 151)

General procedure 1, method 1.

The initial substance: 2-methyl-6-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1F) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 164,7, 149,4, 149,3, 145,0, 136,1, 135,3, 129,6, 128,7, 128,2, 121,9, 120,2, 117,8, 108,2, 76,7, 45,0, 191.

Example 467:

5-Methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 152)

General procedure 1, method 1.

Educt: 5-methyl-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1G) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,3, 150,6, 149,5, 149,2, 146,1, 133,0, 128,3, 123,3, 122,0, 118,8, 113,4, 111,6, 71,9, 45,0, 19,7, 18,6.

Example 468:

N-Benzyloxy-5-methyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 153)

General procedure 1, method 1.

Educt: 5-methyl-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see getting 1G) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,2, 146,1, 136,0, 133,0, 128,8, 128,2, 128,2, 123,2, 122,0, 113,4, 111,6, 76,9, 44,9, 19,7.

Example 469:

5-Bromo-N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 154)

General method 1, method 2.

Source materials: 5-bromo-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1H) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 165,7, 157,2, 149,6, 148,5, 147,4, 134,8, 130,5, 130,2, 129,9, 124,4, 121,9, 118,6, 115,0, 114,1, 113,7, 111,9, 105,5, 71,0, 56,1, 44,7.

Example 470:

N-BAA is siloxy-5-bromo-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 155)

General method 1, method 2.

Source materials: 5-bromo-2-[(pyridine-4-ylmethyl)amino]benzoic acid (see obtaining 1H) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 165,6, 149,6, 148,5, 147,3, 135,8, 134,7, 130,2, 128,8, 128,2, 121,9, 115,2, 113,7, 105,5, 77,0, 44,7.

Example 471:

N-(4-Cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 156)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 165,9, 156,5, 151,2, 149,6, 149,3, 141,7, 136,1, 132,2, 129,2, 121,9, 118,6, 111,1, 110,8, 108,0, 76,0, 42,7.

Example 472:

N-(2-Chloro-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 157)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) hydrochloride and 4-aminoacetyl-3-chlorobenzonitrile (see getting 44).

13C-NMR (DMSO-d6) δ 156,4, 151,2, 149,6, 149,3, 139,4, 136,2, 133,6, 132,6, 131,4, 131,0, 121,9, 117,3, 112,5, 111,1, 107,9, 73,2, 42,7.

Example 473:

N-(4-Cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 158)

General procedure 1, method 1.

Ref the derivative substances: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) hydrochloride and 4-aminoacetyl-3-perbenzoate (see getting 42).

13C-NMR (DMSO-d6) δ 160,1, 151,2, 149,6, 149,3, 136,1, 132,7, 128,6, 121,9, 119,3, 117,4, 112,8, 111,1, 107,9, 69,8, 42,7.

Example 474:

N-(3-Bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 159)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) hydrochloride and 4-aminoacetyl-2-bromobenzonitrile (see getting 43).

13C-NMR (DMSO-d6) δ 165,9, 156,5, 151,2, 149,6, 149,3, 136,1, 134,7, 132,4, 128,0, 124,3, 121,9, 117,1, 113,7, 111,1, 107,9, 75,2, 42,7.

Example 475:

N-(2-Jobensitas)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 160)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) and the hydrochloride of O-(2-jobensis)hydroxylamine (see 20).

13C-NMR (DMSO-d6) δ 156,5, 151,1, 149,6, 149,3, 139,0, 138,3, 136,2, 130,4, 130,2, 128,3, 121,9, 111,1, 108,1, 99,5, 80,2, 42,7.

Example 476:

N-(2-Bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 161)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) and the hydrochloride of O-(2-bromobenzyl)hydroxylamine (Bionet).

13C-NMR (DMSO-d6) δ 156,6, 151,2, 149,7, 149,4, 136,3, 135,3, 132,6, 131,3, 130,4, 127,8, 123,4, 122,0, 111,2 108,2, 76,0, 42,8.

Example 477:

N-(4-Cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 162)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 165,7, 157,1, 156,5, 151,1, 149,6, 149,3, 136,1, 130,4, 129,9, 124,4, 121,9, 118,6, 114,1, 111,8, 111,1, 108,1, 71,0, 56,0, 42,7.

Example 478:

N-(2-Methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 163)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,4, 156,5, 151,0, 150,4, 149,6, 149,3, 136,1, 121,9, 119,1, 111,1, 108,3, 71,8, 42,7, 18,6.

Example 479:

N-Cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 164)

General procedure 1, method 1.

Source materials: 2-[(pyridine-4-ylmethyl)amino]nicotinic acid (see getting 2) and the hydrochloride of O-cyclopentanecarboxylate (see getting 66).13C-NMR (DMSO-d6) δ 165,5, 156,7, 151,0, 149,6, 149,3, 136,0, 122,0, 111,1, 108,3, 79,5, 42,7, 37,6, 28,9, 24,9.

Example 480:

N-Benzylic and-2-(4-forbindelsen)nicotinamide (compound 165)

General procedure 1, method 1.

The initial substance: 2-(4-forbindelsen)nicotinic acid (see 3) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 165,8, 156,8, 151,2, 140,1, 136,0, 135,8, 128,8, 128,2, 127,1, 126,6, 110,7, 107,7, 76,9, 43,7.

Example 481:

N-Benzyloxy-2-(4-chlorobenzylamino)nicotinamide (compound 166)

General procedure 1, method 1.

The initial substance: 2-(4-chlorobenzylamino)nicotinic acid (see obtaining 3A) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 165,8, 156,6, 151,2, 139,4, 136,0, 135,8, 131,0, 128,9, 128,8, 128,2, 128,1, 110,9, 107,9, 76,9, 43,0.

Example 482:

N-Benzyloxy-2-(4-methoxybenzylamine)nicotinamide (compound 167)

General procedure 1, method 1.

The initial substance: 2-(4-methoxybenzylamine)nicotinic acid (see obtaining 4) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 158,1, 156,7, 151,3, 135,9, 135,8, 131,8, 128,8, 128,6, 128,2, 113,7, 110,6, 107,6, 76,9, 54,9, 43,3.

Example 483:

N-Benzyloxy-2-(isoquinoline-5-ylamino)nicotinamide (compound 168)

General procedure 1, method 1.

The initial substance: 2-(isoquinoline-5-ylamino)nicotinic acid (see obtaining 3B) and hydrochloride O-benzylhydroxylamine (Aldrich).

13 C-NMR (DMSO-d6) δ 154,4, 152,8, 150,9, 142,9, 136,7, 135,7, 134,4, 128,9, 128,8, 128,3, 127,5, 121,4, 119,9, 114,1, 113,9, 109,5, 77,1.

Example 484:

N-(4-Cyano-2-methoxybenzyloxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 169)

General procedure 1, method 1.

Source materials: 3-[(pyridine-4-ylmethyl)amino]isonicotinoyl acid (see getting 1I) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 157,2, 149,6, 148,4, 142,1, 136,3, 135,0, 130,4, 129,9, 124,4, 121,9, 120,6, 118,6, 114,1, 111,9, 71,0, 56,1, 44,5.

Example 485:

N-Benzyloxy-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 170)

General procedure 1, method 1.

Source materials: 3-[(pyridine-4-ylmethyl)amino]isonicotinoyl acid (see getting 1I) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 149,6, 148,5, 142,1, 136,3, 135,8, 135,0, 128,9, 128,2, 122,0, 120,5, 118,9, 76,9, 44,5.

Example 486:

N-(2-Methylthiazole-4-ylethoxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 171)

General procedure 1, method 1.

Source materials: 3-[(pyridine-4-ylmethyl)amino]isonicotinoyl acid (see getting 1I) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,4, 150,4, 149,6, 148,5, 142,0, 136,3, 134,9, 12,0, 120,6, 119,2, 118,9, 71,7, 44,5, 18,6.

Example 487:

N-Benzyloxy-2-(4-forbindelsen)benzamide (compound 172)

General procedure 1, method 1.

The initial substance: 2-(4-forbindelsen)benzoic acid (see getting 1J) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,2, 161,1, 148,6, 135,9, 135,6, 132,5, 128,9, 128,8, 128,2, 128,0, 115,1, 114,5, 113,1, 111,5, 76,9, 45,2.

Example 488:

N-(4-Cyanobenzyl)-2-(4-forbindelsen)benzamide (compound 173)

General method 1, method 2.

The initial substance: 2-(4-forbindelsen)benzoic acid (see getting 1J) and hydrochloride, O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,4, 161,1, 148,6, 141,8, 135,5, 132,6, 132,1, 129,1, 128,9, 128,0, 118,7, 115,1, 114,5, 112,8, 111,5, 110,7, 75,9, 45,1.

Example 489:

2-(4-Forbindelsen)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 174)

General procedure 1, method 1.

The initial substance: 2-(4-forbindelsen)benzoic acid (see getting 1J) and hydrochloride, O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 167,2, 165,3, 161,1, 150,5, 148,5, 135,5, 132,5, 128,9, 128,0, 25 118,9, 115,1, 114,5, 113,1, 111,5, 71,9, 45,2, 18,6.

Example 490:

N-Benzyloxy-2-(3-cyano-4-forbindelsen)benzamide (compound 175)

General method 1, method 2.

The initial substance: 2-(3-cyano-4-forbindelsen)benzoic acid (see getting 1K) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,1, 161,3, 148,0, 137,6, 135,9, 134,6, 132,5, 132,0, 128,8, 128,2, 128,1, 116,6, 114,9, 114,0, 113,6, 111,4, 99,9, 99,7, 76,9, 44,4.

Example 491:

N-(2-Bromobenzylamine)-2-(3-cyano-4-forbindelsen)benzamide (compound 176)

General method 1, method 2.

The initial substance: 2-(3-cyano-4-forbindelsen)benzoic acid (see getting 1K) and chloride 1-[(ammoniac)methyl]-2-bromine benzol (Bionet).

13C-NMR (DMSO-d6) δ 161,4, 148,1, 137,7, 135,4, 134,7, 132,6, 132,5, 132,1, 131,2, 130,3, 128,3, 127,8, 123,2, 116,7, 115,0, 114,1, 113,5, 111,5, 100,0, 99,8, 75,9, 44,5.

Example 492:

Methyl ester 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (compound 177)

General procedure 1, method 1.

The initial substance: methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid (see obtaining 1L) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,2, 164,0, 159,9, 148,4, 136,2, 135,9, 133,6, 132,5, 130,0, 5 128,8, 128,7, 128,2, 128,0, 117,9, 117,1, 114,7, 113,3, 111,5, 76,9, 52,3, 44,8.

Example 493:

Methyl ester 5-[(2-cyclopentanecarbonitrile)-methyl]-2-fermenting acid (compound 178)

General procedure 1, method 1.

The initial substance: methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid (see obtaining 1L) hydrochloride and O-cyclopentanecarboxylate (see getting 66).

1H-NMR (DMSO-d6) δ of 11.45 (s, 1H), 7,87 (m, 2H), 7.62mm (m, 1H), 7,40 (d, 1H), 7,31 (DD, 1H), 7,21 (t, 1H), 6,55 (m, 2H), of 4.44 (d, 2H), 3,81 (s, 3H), of 3.77 (d, 2H), measuring 2.20 (m, 1H), 1,8-1,2 (m, 8H).

Example 494:

Methyl ester 2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzoic acid (compound 179)

General procedure 1, method 1.

The initial substance: methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid (see obtaining 1L) and 1-[(ammoniac)methyl]-4-forbesall (Bionet).

1H-NMR (DMSO-d6) δ 11,57 (s, 1H), 7,88 (m, 2H), 7.62mm (m, 1H), 7,51 (m, 2H), 7,32 (DD, 1H), 7,27-7,17 (m, 4H), to 6.58 (m, 2H), 4,91 (s, 2H), 4,45 (d, 2H), of 3.84 (s, 3H).

Example 495:

Methyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl]-2-Formentera acid (compound 180)

General procedure 1, method 1.

The initial substance: methyl ester 5-[(2-carboxyphenylazo)methyl]-2-fermenting acid (see obtaining 1L) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,4, 164,0, 159,8, 148,4, 141,9, 136,2, 133,5, 132,6, 132,2, 130,0, 129,1, 128,1, 118,7, 117,9, 117,1, 114,7, 113,0, 111,5, 110,8, 75,9, 52,3, 44,8.

Example 496:

5-[(2-Cyclopentanecarbonitrile)methyl]-2-Formentera acid (compound 181)

Methyl ester 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid (example 493, 511 mg) was dissolved in THF (15 ml) and water (5 ml). Add lithium hydroxide (122 mg) and the mixture heated to 60°C. the Reaction mixture is stirred at this temperature for 15 h, cooled to room temperature and concentrate under reduced pressure. The residue is diluted with water and add 1M hydrochloric acid to the sludge. The solid is separated by filtration and washed with water, dried in high vacuum and get listed in the title compound (380 mg) as a white powder.13C-NMR (DMSO-d6) δ 166,9, 165,0, 160,0, 148,4, 135,9, 133,0, 132,4, 130,1, 128,0, 119,1, 116,9, 114,6, 113,4, 111,5, 79,4, 44,8, 37,6, 28,9, 24,9.

Example 497:

2-Fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzoic acid (compound 182)

Get the method similar to that described for an example 496, based on the methyl ester 2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzoic acid (example 494).

13C-NMR (DMSO-d6) δ 167,3, 165,0, 162,0, 160,0, 148,5, 135,9, 133,0, 132,6, 132,3, 131,2, 130,1, 128,1, 119,2, 116,9, 115,1, 114,7, 113,2, 111,5, 76,1, 44,8, 25,1.

Example 498:

5-[(2-Benzyl what xcarnation)methyl]-2-Formentera acid (compound 183)

Get the method similar to that described for an example 496, based on the methyl ester 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (example 492).

13C-NMR (DMSO-d6) δ 167,2, 165,0, 160,0, 148,4, 135,9, 133,0, 132,5, 130,1, 128,8, 128,2, 128,0, 119,1, 116,9, 114,7, 113,2, 111,5, 76,9, 44,8.

Example 499:

5-[(2-Benzyloxycarbonylamino)methyl]-2-fluoro-N-(2-hydroxyethyl)benzamide (compound 184)

5-[(2-Benzyloxycarbonylamino)methyl]-2-fermenting acid (example 498, of 96.5 mg) and 1-hydroxybenzotriazole (36 mg) was dissolved in DMF (1.0 ml). Add 2-aminoethanol (15 μl), N-methylmorpholin (28 μl) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (50,1 mg) in that order. The reaction mixture was shaken at room temperature for 15 hours. The solvent is evaporated under reduced pressure and the residue is dissolved in dichloromethane and evaporated onto silica gel. Cleaning method column chromatography on silica gel (elution with 50-100% EtOAc in petroleum ether) gives specified in the header of the connection.13C-NMR (DMSO-d6) δ 167,2, 163,5, 158,1, 148,5, 135,9, 132,5, 130,7, 129,1, 128,8, 128,6, 128,2, 128,0, 123,7, 116,0, 114,6, 113,2, 111,5, 76,9, 59,5, 45,0, 42,0.

Example 500:

5-[(2-Benzyloxycarbonylamino)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 185)

Get the method similar to that described for example 499, starting from 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (example 498) and 3-aminopropan-1-ol.

13C-NMR (DMSO-d6) δ 167,2, 163,4, 158,0, 148,5, 135,8, 132,5, 130,5, 128,8, 128,5, 128,2, 128,0, 124,0, 116,0, 114,6, 113,2, 111,5, 76,9, 58,5, 45,0, 36,6, 32,1.

Example 501:

5-[(2-Benzyloxycarbonylamino)methyl]-2-fluoro-N-(4-hydroxybutyl)benzamide (compound 186)

Get the method similar to that described for example 499, starting from 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (example 498) and 4-aminobutane-1-ol.

13C-NMR (DMSO-d6) δ 167,2, 163,4, 157,9, 148,5, 135,9, 135,8, 132,5, 130,4, 128,8, 128,4, 128,2, 128,0, 124,2, 116,0, 114,6, 113,2, 111,5, 76,9, 60,3, 45,0, 39,0, 29,8, 25,6.

Example 502:

5-[(2-Benzyloxycarbonylamino)methyl]-N-(3-dimethylaminopropyl)-2-perbenzoic (compound 187)

Get the method similar to that described for example 499, starting from 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (example 498) and 3-(N,N-dimethylamino)-1-Propylamine.

13C-NMR (DMSO-d6) δ 166,8, 163,5, 158,0, 148,4, 136,0, 135,9, 132,4, 130,7, 128,8, 128,5, 128,2, 128,0, 123,8, 116,0, 114,6, 113,1, 111,4, 76,8, 55,5, 45,0, 43,4, 37,0, 25,2.

Example 503:

5-[(2-Cyclopentanecarbonitrile)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 188)

Get the method similar to that described for example 499, starting from 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid (example 496) and 3-aminopropan-1-ol.

13C-NMR (DMSO-d6) δ 166,9, 163,4, 157,9, 148,4, 135,8, 132,4, 130,5, 128,4, 127,9, 124,0, 116,0, 114,6, 113,3, 111,5, 79,4, 58,5, 44,9, 37,6, 36,6, 32,1, 28,9, 24,9.

Example 504:

N-Cyclopentyloxy-2-[4-fluoro-3-(4-methylpiperazin-1-carbonyl)benzoylamino]benzamide (compound 189)

Get the method similar to that described for example 499, starting from 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid (example 496) and 1-methylpiperazine.

13C-NMR (DMSO-d6) δ 163,8, 156,4, 148,3, 136,3, 132,3, 129,8, 127,9, 126,9, 123,7, 115,8, 114,6, 113,3, 111,5, 79,4, 54,5, 54,1, 46,3, 45,4, 44,8, 41,1, 37,6, 28,9, 24,9.

Example 505:

N-Cyclopentyloxy-2-[4-fluoro-3-(morpholine-4-carbonyl)benzoylamino]benzamide (compound 190)

Get the method similar to that described for example 499, starting from 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid (example 496) and research.

13C-NMR (DMSO-d6) δ 166,9, 163,9, 156,5, 148,4, 136,4, 132,3, 129,9, 128,0, 127,1, 123,4, 115,8, 114,6, 113,4, 111,5, 79,4, 66,1, 65,9, 46,9, 44,8, 41,7, 37,6, 28,9, 24,9.

Example 506:

N-Benzyloxy-2-(4-methoxybenzylamine)benzamide (compound 191)

Overall Modica 1, method 1.

The initial substance: 2-(4-methoxybenzylamine)benzoic acid (see getting 1M) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,3, 158,2, 148,7, 135,9, 132,5, 131,1, 128,8, 128,4, 128,2, 127,9, 114,3, 113,8, 112,8, 111,5, 76,8, 54,9, 45,5.

Example 507:

2-(4-Methoxybenzylamine)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 192)

General procedure 1, method 1.

The initial substance: 2-(4-methoxybenzylamine)benzoic acid (see getting 1M) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 167,3, 165,3, 158,2, 150,5, 148,7, 132,5, 131,1, 128,4, 128,0, 118,8, 114,3, 113,8, 112,8, 111,4, 71,8, 54,9, 45,5, 18,6.

Example 508:

N-Benzyloxy-2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzamide (compound 193)

General procedure 1, method 1.

Source materials: 2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzoic acid (see getting 1N) and hydrochloride O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,3, 154,4, 148,9, 135,8, 132,7, 131,8, 128,7, 128,1, 127,9, 126,7, 125,8, 125,2, 125,1, 123,4, 122,0, 114,4, 112,7, 111,5, 103,7, 76,8, 55,5, 44,0.

Example 509:

N-(4-Cyanobenzyl)-2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzamide (compound 194)

General procedure 1, method 1.

Source materials: 2-[(4-methoxynaphthalene-1-ylmethyl)aminobenzoic acid (see getting 1N) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,5, 154,4, 148,9, 141,7, 132,8, 132,1, 131,8, 129,1, 127,9, 126,7, 125,9, 125,8, 125,2, 125,1, 123,4, 122,0, 118,6, 114,4, 112,4, 111,6, 110,7, 103,6, 75,8, 55,5, 44,0.

Example 510:

2-[(2,3-Dihydrobenzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound No. 195)

General procedure 1, method 1.

Source materials: 2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzoic acid (see 10) and 1-[(ammoniac)methyl]-4-torbenson chloride (Bionet).

13C-NMR (DMSO-d6) δ 167,3, 162,0, 158,7, 148,7, 132,5, 132,3, 131,1, 131,0, 127,7, 125,4, 115,0, 114,3, 112,7, 111,5, 108,6, 76,0, 70,8, 45,8, 29,0.

Example 511:

N-(4-Cyanobenzyl)-2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzamide (compound 196)

General procedure 1, method 1.

Source materials: 2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzoic acid (see 10) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,5, 158,7, 148,8, 141,8, 132,7, 132,1, 131,0, 129,1, 127,9, 127,4, 126,8, 124,0, 118,6, 114,3, 112,5, 111,5, 110,7, 108,6, 75,9, 70,8, 45,8, 29,0.

Example 512:

2-[(Benzofuran-5-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 197)

General method 1, method 2.

Source materials: 2-[(benzofuran-5-ylmethyl)amino]benzoic acid (see getting 1P) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (motri 10).

13C-NMR (DMSO-d6) δ 167,5, 153,4, 148,7, 146,2, 133,9, 132,1, 132,0, 129,2, 129,1, 127,9, 127,3, 123,6, 119,5, 118,6, 114,4, 111,6, 111,1, 110,7, 106,6, 75,9, 46,0.

Example 513:

2-[(Benzofuran-5-ylmethyl)amino]-N-benzyloxybenzoate (compound 198)

General method 1, method 2.

Source materials: 2-[(benzofuran-5-ylmethyl)amino]benzoic acid (see getting 1P) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,3, 153,4, 148,7, 146,2, 135,9, 134,0, 132,5, 128,8, 128,2, 127,9, 127,3, 123,7, 119,5, 114,4, 112,9, 111,5, 111,1, 106,6, 76,9, 46,0.

Example 514:

2-[(Benzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 199)

General method 1, method 2.

Source materials: 2-[(benzofuran-5-ylmethyl)amino]benzoic acid (see getting 1P) and 1-[(ammoniac)methyl]-4-torbenson chloride (Bionet).

13C-NMR (DMSO-d6) δ 167,3, 162,0, 153,4, 148,7, 146,2, 134,0, 132,5, 132,3, 131,1, 131,0, 127,6, 123,7, 119,5, 115,0, 114,4, 112,9, 111,6, 111,1, 106,6, 76,1, 46,0.

Example 515:

N-(4-Cyanobenzyl)-2-[(2-oxo-2H-chromen-6-ylmethyl)amino]benzamide (compound 200)

General procedure 1, method 1.

Source materials: 2-[(2-oxo-2H-chromen-6-ylmethyl)amino]benzoic acid (see getting 1Q), and hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 159,9, 152,5, 148,5, 144,1, 141,8, 135,9 132,6, 132,1, 130,7, 129,1, 128,0, 126,5, 118,6, 118,6, 116,4, 116,3, 114,7, 112,8, 111,5, 110,7, 75,9, 45,2

Example 516:

N-(4-Chlorobenzoyloxy)-2-(4-cyanobenzylidene)benzamide (compound 201)

To a stirred mixture of 4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)benzonitrile (getting a 7D, 319 mg) and the hydrochloride of O-(4-Chlorobenzyl)hydroxylamine (9, 267 mg) in DMF (10 ml) is added N-ethyldiethanolamine (0.4 ml). The reaction mixture is heated to 100°C and stirred for 17 hours. The mixture is cooled to room temperature and add water. Saducees light brown substance was separated by filtration and recrystallized from ethanol, to obtain specified in the title compound as a white solid.13C-NMR (DMSO-d6) δ 148,2, 145,9, 135,1, 132,8, 132,5, 132,3, 130,6, 128,2, 128,0, 127,7, 118,8, 114,8, 113,2, 111,4, 109,5, 75,9, 45,4.

Example 517:

2-[(3,5-Dichloropyridine-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 202)

General method 1, method 2.

Source materials: 2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzoic acid (see getting 1R) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (CDCl3) δ 167,1, 150,8, 148,6, 148,0, 142,5, 133,5, 133,1, 127,6, 118,1, 115,9, 113,0, 112,0, 72,9, 41,9, 19,1.

Example 518:

N-Benzyloxy-2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzamide (with the Association 203)

General method 1, method 2.

Source materials: 2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzoic acid (see getting 1R) and O-benzylhydroxylamine (Aldrich).

13C-NMR (CDCl3) δ 148,5, 148,0, 142,5, 135,5, 133,5, 133,1, 129,2, 128,8, 128,7, 127,4, 115,9, 112,0, 78,3, 41,9.

Example 519:

2-[(2-Bromopyridin-4-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 204)

General procedure 1, method 1.

Source materials: 2-[(2-bromopyridin-4-ylmethyl)amino]benzoic acid (see getting 1S) and chloride 1-[(ammoniac)methyl]-4-torbenson (Bionet).

13C-NMR (DMSO-d6) δ 167,0, 162,0, 153,5, 150,3, 147,8, 141,5, 132,5, 132,2, 131,1, 128,1, 125,8, 121,7, 115,0, 115,0, 113,6, 111,4, 76,0, 44,3.

Example 520:

N-(4-Cyano-2-methoxybenzyloxy)-2-[(2-hydroxypyridine-4-ylmethyl)amino]benzamide (compound 205)

General procedure 1, method 1.

Source materials: 2-[(2-hydroxypyridine-4-ylmethyl)amino]benzoic acid (see getting 1T) and the hydrochloride of 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 167,3, 162,4, 157,1, 153,7, 148,2, 135,0, 132,5, 130,3, 130,0, 128,0, 124,4, 118,7, 115,9, 114,7, 114,0, 113,1, 111,7, 111,4, 104,1, 70,9, 56,0, 44,8.

Example 521:

2-[(2-Aminopyridine-4-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 206)

General IU the of hoëdic 1A.

The initial substance: 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7B) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 159,9, 149,4, 148,6, 147,7, 141,9, 132,6, 132,2, 129,1, 127,9, 118,6, 114,5, 112,5, 111,5, 110,7, 110,5, 105.2, 75,9, 45,2.

Example 522:

N-(4-Forbindelse)-2-[(2-morpholine-4-espiridion-4-ylmethyl)amino]benzamide (compound 207)

General procedure 1, method 1.

Source materials: 2-[(2-morpholine-4-espiridion-4-ylmethyl)amino]benzoic acid (see getting 1U) and 1-[(ammoniac)methyl]-4-forbesall (Bionet).

13C-NMR (DMSO-d6) δ 167,2, 162,0, 159,4, 150,3, 148,6, 147,6, 132,5, 132,2, 131,1, 128,0, 115,0, 114,7, 113,2, 112,1, 111,6, 104,9, 76,1, 65,8, 45,5, 45,1.

Example 523:

N-Cyclopentyloxy-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (compound 208)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (600 mg, see getting 7b) in pyridine (7 ml) add methanesulfonanilide (280 mg) and the reaction mixture was stirred at room temperature for 15 hours. The solvent is evaporated under reduced pressure and the residue is dissolved in EtOAc and washed with water and saturated salt solution. The organic layer is dried (MgSO4) and evaporated under reduced pressure. The remaining solid fuel is the yellow substance dissolved in a mixture of hot EtOAc (50 ml) and DMF (4 ml). Upon cooling, a solid substance was separated by filtration and dried in vacuum, obtaining N-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]methanesulfonamide. Stage 2: this interim anhydride in turn specified in the title compound interactions hydrochloride O-cyclopentanecarboxylate (see getting 66)using General method 1A.13C-NMR (DMSO-d6) δ 166,8, 152,9, 152,6, 148,3, 132,4, 127,9, 115,2, 114,8, 113,3, 111,4, 110,1, 79,4, 45,0, 41,5, 37,6, 28,9, 24,9.

Example 524:

N-(4-Cyanobenzyl)-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (compound 209)

A General method 1A.

The initial substance: N-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]methanesulfonamide (see example 523, stage 1) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,4, 152,9, 152,5, 148,3, 145,6, 141,8, 132,6, 132,2, 129,1, 128,0, 118,7, 115,1, 114,9, 112,9, 111,5, 110,7, 110,2, 75,9, 45,0, 41,6.

Example 525:

N-(4-Cyanobenzyl)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 210)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (7.0 g, see getting 7b) in pyridine (70 ml) was added methyl isocyanate (5 EQ.) 45 minutes After some time, add another Metelitza the nut (20 EQ.) before using up all of the original substance. The solvent is evaporated under reduced pressure. The remaining solid is washed with EtOAc (50 ml) and after drying in a vacuum get 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]-3-metalmachine. Stage 2: this interim anhydride in turn specified in the title compound interaction with the hydrochloride of O-(4-cyanobenzyl))hydroxylamine (see 10), using the General method 1A.13C-NMR (DMSO-d6) δ 167,4, 155,3, 153,7, 151,2, 148,5, 146,6, 141,8, 132,6, 132,2, 129,2, 128,0, 118,7, 115,1, 114,7, 112,9, 111,5, 110,8, 109,1, 76,0, 45,2, 25,8.

Example 526:

N-(4-Cyano-2-methoxybenzyloxy)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 211)

A General method 1A.

Educt: 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]-3-metalmachine (see example 525, stage 1) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 167,3, 157,1, 155,3, 153,7, 151,2, 148,5, 146,6, 132,6, 130,3, 130,0, 128,0, 124,4, 118,7, 115,0, 114,7, 114,0, 112,9, 111,7, 111,5, 109,1, 70,9, 56,0, 45,3, 25,8.

Example 527:

N-Cyclopentyloxy-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 212)

A General method 1A.

Educt: 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]-3-metalmachine (see example 525, stage 1) and the hydrochloride of O-qi is lopetusmerkkien (see getting 66).

13C-NMR (DMSO-d6) δ 166,9, 155,3, 153,7, 151,3, 148,5, 146,5, 132,4, 127,9, 115,1, 114,7, 113,3, 111,4, 109,1, 79,4, 45,3, 37,6, 28,9, 25,8, 24,9.

Example 528:

N-(2,3-Debtor-4-methylbenzylamino)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 213)

A General method 1A.

Educt: 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]-3-metalmachine (see example 525, stage 1) and the hydrochloride of O-(2,3-debtor-4-methylbenzyl)hydroxylamine (see getting 15).

13C-NMR (DMSO-d6) δ 167,3, 155,3, 153,8, 151,2, 148,5, 146,6, 132,5, 128,0, 127,2, 126,1, 125,8, 122,6, 115,1, 114,8, 113,1, 111,5, 109,2, 69,8, 45,3, 25,8, 13,8.

Example 529:

Ethyl ester of [3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 214)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (600 mg, see getting 7b) in pyridine (7 ml) is added ethyl ether isocyanatoacetate acid (0.4 ml). The reaction mixture was stirred at room temperature for 3 hours and the solvent is evaporated under reduced pressure. The residue is dissolved in EtOAc and washed with water and saturated salt solution. The organic layer is dried (MgSO4) and evaporated under reduced pressure. The oil obtained is treated with EtOAc (3 ml) and receive the precipitate, which is separated fil the management and dried in vacuum, getting ethyl ester {3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]ureido}acetic acid (0,53 g). Stage 2: this interim anhydride in turn specified in the title compound interaction with the hydrochloride of O-(4-cyanobenzyl))hydroxylamine (see 10)using General method 1A.13C-NMR (DMSO-d6) δ 170,3, 167,4, 154,8, 153,5, 151,4, 148,5, 146,7, 141,8, 132,7, 132,2, 129,1, 128,0, 118,6, 115,4, 114,8, 112,9, 111,5, 110,7, 109,3, 76,0, 60,3, 45,2, 41,2, 14,0.

Example 530:

Ethyl ester of (3-(4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (compound 215)

A General method 1A.

The original substances: ethyl ester {3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]ureido}acetic acid (see example 529, stage 1) hydrochloride and O-cyclopentanecarboxylate (see getting 66).

13C-NMR (DMSO-d6) δ 170,3, 166,9, 154,8, 153,5, 151,5, 148,5, 146,6, 132,4, 127,9, 115,4, 114,7, 113,3, 111,4, 109,2, 79,4, 60,3, 45,2, 41,2, 37,6, 28,9, 24,9, 14,0.

Example 531:

[3-(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 216)

To a stirred suspension of ethyl ester of [3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)ureido]acetic acid (example 529, 188 mg) in methanol (4 ml) is added 2M water hydroc the ID of sodium (2 ml). The reaction mixture was stirred at room temperature for 15 minutes Add water (6 ml) and adjusted pH of the mixture to 5 by adding 4M hydrochloric acid. Received saducees substance separated by filtration and dried in high vacuum, getting listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 171,7, 167,5, 154,7, 153,5, 151,3, 148,4, 146,7, 141,9, 132,6, 132,1, 129,1, 128,0, 118,7, 115,3, 114,8, 112,8, 111,5, 110,7, 109,2, 75,9, 45,3, 41,4

Example 532:

(3-{4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (compound 217)

Get the method similar to that described for an example 531, based on the ethyl ester of (3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (example 530).

13C-NMR (DMSO-d6) δ 171,6, 166,9, 154,8, 153,6, 151,4, 148,5, 146,7, 132,4, 128,0, 115,3, 114,8, 113,4, 111,5, 109,3, 79,5, 45,3, 41,2, 37,6, 29,0, 24,9.

Example 533:

2-[3-(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]ethyl ester 2-methylacrylate acid (compound 218)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (1.2 g, see getting 7b) in pyridine add isocyanatomethyl methacrylate (0,76 ml). The reaction mixture is heated to 40°C and stirred for 2 hours. Add isocyanatomethyl ethacrylate (0.1 ml) and continue stirring for 2 hours. The solvent is evaporated under reduced pressure and add to the residue EtOAc (10 ml). Removing from the walls of the formed solid substance, it is separated by filtration and dried in vacuum, obtaining 2-{3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]ureido}ethyl ester 2-methylacrylate acid (1.78 g). Stage 2: this interim anhydride in turn specified in the title compound interaction with the hydrochloride of O-(4-cyanobenzyl))hydroxylamine (see 10)using General method 1A.13C-NMR (DMSO-d6) δ 167,5, 166,5, 154,8, 153,7, 151,4, 148,6, 146,6, 141,9, 135,8, 132,8, 132,3, 129,2, 128,1, 125,9, 118,8, 115,4, 114,9, 113,0, 111,6, 110,9, 109,4, 76,1, 63,7, 45,4, 38,0, 18,0.

Example 534:

2-(3-(4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)ethyl ester 2-methylacrylate acid (compound 219)

A General method 1A.

The initial substance: 2-{3-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]ureido}ethyl ester 2-methylacrylate acid (example 533, stage 1) hydrochloride and O-cyclopentyl-5 methylhydroxylamine (see getting 66).

13C-NMR (DMSO-d6) δ 166,9, 166,3, 154,7, 153,6, 151,4, 148,5, 146,5, 135,7, 132,4, 127,9, 125,8, 115,3, 114,7, 113,3, 111,4, 109,2, 79,4, 63,6, 45,3, 37,9, 37,6, 28,9, 24,9, 17,8.

Example 535:

N-(4-Cyanobenzyl)-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}amino)benzamide (compound 220)

To a stirred suspension of 2-[3-(4-{[2-(4-cyanobenzoate-carbarnoyl)phenylamino]methyl}pyridine-2-yl)ureido]ethyl ester 2-methylacrylate acid (example 533, 500 mg) in methanol (10 ml) is added 2M aqueous sodium hydroxide (5 ml). The reaction mixture was stirred at room temperature for 20 min, the pH of the mixture was adjusted to 5 by adding 4M hydrochloric acid, and add water (15 ml). Received saducees substance separated by filtration, dried in vacuum and get listed at the beginning of the connection.13C-NMR (DMSO-d6) δ 167,4, 154,8, 153,8, 151,1, 148,6, 146,7, 141,8, 132,6, 132,1, 129,1, 128,0, 118,6, 115,1, 114,8, 113,0, 111,6, 110,8, 109,3, 76,0, 60,2, 45,3, 41,8.

Example 536:

N-Cyclopentyloxy-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}amino)benzamide (compound 221)

Get the method similar to that described for an example 535, based on 2-(3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)ethyl ester 2-methylacrylate acid (example 534).

13C-NMR (DMSO-d6) δ 166,9, 154,8, 153,8, 151,2, 148,5, 146,7, 132,4, 127,9, 115,1, 114,7, 113,4, 111,4, 109,3, 79,5, 60,2, 45,4, 41,8, 37,6, 29,0, 24,9.

Example 537:

(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-ylcarbonyl)methyl ester acetic acid (compound 222)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ILM is Teal)-1H-benzo[d][1,3]oxazin-2,4-dione (600 mg, see getting 7b) in pyridine (5 ml) add acetoxyacetyl (0,29 ml). The reaction mixture was stirred at room temperature for 30 minutes the Solvent is evaporated under reduced pressure. The remaining oil is dissolved in EtOAc and washed with water and saturated salt solution. The organic layer is concentrated to about 10 ml under reduced pressure. The obtained solid substance was separated by filtration and dried in vacuum, obtaining [4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-ylcarbonyl]methyl ester of acetic acid. Stage 2: the intermediate anhydride in turn specified in the title compound interaction with the hydrochloride of O-(4-cyanobenzyl))hydroxylamine (see 10)using General method 1A.13C-NMR (DMSO-d6) δ 169,9, 167,4, 166,1, 151,7, 151,5, 148,5, 147,9, 141,8, 132,6, 132,2, 129,2, 128,0, 118,7, 117,8, 114,8, 113,0, 111,4, 110,7, 75,9, 62,3, 45,3, 20,3.

Example 538:

{4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-ylcarbonyl}methyl ether acetic acid (compound 223)

A General method 1A.

Source materials: [4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-ylcarbonyl]methyl ester acetic acid (see example 537, stage 1) hydrochloride and O-cyclopentyl-5 methylhydroxylamine (see getting 66).

13C-NMR (DMSO-d6) δ 169,9, 166,9, 166,1, 51,7, 151,6, 148,4, 147,9, 132,4, 128,0, 117,8, 114,7, 113,4, 111,4, 79,4, 62,3, 45,3, 37,6, 28,9, 24,9, 20,3

Example 539:

N-(4-Cyanobenzyl)-2-{[2-(2-hydroxyacetylamino)pyridine-4-ylmethyl]amino}benzamide (compound 224)

(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-ylcarbonyl)methyl ester acetic acid (example 537, 52 mg) is suspended in methanol (2 ml) and add 2M aqueous sodium hydroxide (1 ml). The reaction mixture was stirred at room temperature for 10 minutes Bring the pH of the mixture to 7 by adding 2M hydrochloric acid. The obtained precipitate was separated by filtration and dried in vacuum, obtaining specified in the header of the connection.13C-NMR (DMSO-d6) δ 171,2, 167,5, 151,7, 151,3, 148,6, 148,1, 141,9, 132,8, 132,3, 129,3, 128,1, 118,8, 118,1, 114,9, 113,0, 111,6, 111,0, 110,9, 76,1, 61,6, 45,4.

Example 540:

Ethyl ester of 4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)carbamino acid (compound 225)

To a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (200 mg, see getting 7b) in pyridine (5 ml) add ethylchloride (71 μl). The reaction mixture was stirred at room temperature for 60 minutes Add ethylchloride (60 ml) and continue stirring for 30 minutes Add the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (1 EQ., see receipt is 10) and the reaction mixture was stirred at room temperature for 15 hours. The solvent is evaporated under reduced pressure. The residue is dissolved in EtOAc and washed with water and saturated salt solution, dried

(MgSO4) and evaporated under reduced pressure. The remaining oil is treated with ethanol (2 ml) and the resulting solid is separated by filtration and dried in vacuum, obtaining specified in the header of the connection.1H-NMR (DMSO-d6) δ 11,67 (s, 1H), there is a 10.03 (s, 1H), 8,17 (d, 1H), to 7.93 (t, 1H), 7,9 - 7,8 (m, 3H), of 7.69 (d, 2H), 7,37 (d, 1H), 7,21 (t, 1H), 6,97 (d, 1H), 6,55 (t, 1H), of 6.52 (d, 1H), 5,04 (s, 2H), of 4.44 (d, 2H), 4,11 (kV, 2H), to 1.21 (t, 3H).

Example 541:

N-(4-Cyanobenzyl)-2-{[2-(cyclopropanecarbonyl)pyridine-4-ylmethyl]amino}benzamide (compound 226)

To a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (200 mg, see getting 7b) in pyridine (5 ml) add cyclopropanecarbonitrile (80 ál). The reaction mixture was stirred at room temperature for 20 minutes Add cyclopropanecarbonitrile (20 ml) and continue stirring for 30 minutes Add the hydrochloride cyanobenzylidene (1 EQ., see 10) and the reaction mixture was stirred at room temperature for 15 hours. The solvent is evaporated under reduced pressure. The residue is dissolved in EtOAc and washed with water and saturated salt solution, dried

(MgSO4) and evaporated PR is the reduced pressure. The crude product was then purified by the method of column chromatography on silica gel (elution from 0 to 100% EtOAc in heptane) and get listed in the title compound in the form of foam.13C-NMR (DMSO-d6) δ 172,4, 167,4, 152,3, 151,2, 148,5, 147,8, 141,8, 132,7, 132,1, 129,2, 128,0, 118,7, 117,3, 114,8, 112,9, 111,5, 111,3, 110,8, 76,0, 45,4, 14,0, 7,5.

Example 542:

N-Cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)-pyridine-4-ylmethyl]amino}benzamide (compound 227)

Step 1: to a stirred solution of 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (1.1 g, see getting 7b) in pyridine (15 ml) add cyclopropanecarbonitrile (512 mg). The reaction mixture was stirred at room temperature for 30 min and the solvent is evaporated under reduced pressure. The remaining oil is dissolved in EtOAc and washed with water and saturated salt solution. The organic layer is concentrated under reduced pressure and the obtained solid substance was separated by filtration and dried in vacuum, obtaining [4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]amide cyclopropanecarbonyl acid. Stage 2: intermediate obtained above anhydride in turn specified in the title compound interaction with O-cyclopentyl-methylhydroxyethylcellulose (see getting 66)using General method 1A.13C-NMR (DMSO-d6) δ 172,4, 166,9, shall be 152.3, 15,3, 148,5, 147,8, 132,4, 127,9, 117,3, 114,7, 113,3, 111,4, 111,3, 79,4, 45,4, 37,6, 28,9, 24,9, 14,1, 7,4.

Example 543:

N-Cyclopentyloxy-2-({2-[2-(2,5-dioxoimidazolidin-4-yl)acetylamino]pyridine-4-ylmethyl}amino)benzamide (compound 228)

Get the method similar to that described for an example 541. The initial substance: 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7b), as-5-acetylchloride (Lancaster) and hydrochloride O-cyclopentyl-methylhydroxylamine (see getting 66).

13C-NMR (DMSO-d6) δ 175,6, 168,2, 166,9, 157,5, 152,0, 151,5, 148,5, 147,8, 132,4, 128,0, 124,2, 117,6, 114,8, 113,3, 111,5, 79,4, 54,3, 45,5, 37,6, 28,9, 24,9.

Example 544:

2-[(2-Aminopyridine-4-ylmethyl)amino]-N-Cyclopentasiloxane (compound 229)

A General method 1A.

The initial substance: 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7B) and hydrochloride O-cyclopentanecarboxylate (see getting 66).

13C-NMR (DMSO-d6) δ 167,0, 159,9, 149,5, 148,7, 147,7, 132,4, 127,9, 114,5, 113,0, 111,4, 110,5, 105,2, 79,4, 45,2, 37,6, 28,9, 24,9.

Example 545:

N-Benzyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 230)

General method 1, method 2.

Source materials: 2-[(quinoline-4-ylmethyl)amino]benzoic acid (see receiving IV) hydrochloride and O-benzylhydroxylamine Aldrich).

13C-NMR (DMSO-d6) δ 167,2, 150,4, 148,5, 147,7, 144,8, 136,0, 132,6, 129,7, 129,3, 128,9, 128,3, 128,1, 126,6, 126,2, 123,6, 118,7, 114,9, 113,4, 111,6, 76,9, 42,9.

Example 546:

N-(4-Cyanobenzyl)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 231)

General method 1, method 2.

Source materials: 2-[(quinoline-4-ylmethyl)amino]benzoic acid (see receiving IV) and O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,0, 150,2, 148,4, 147,6, 144,7, 141,9, 132,6, 132,1, 129,6, 129,2, 129,1, 128,1, 126,5, 126,1, 123,5, 118,6, 118,6, 114,8, 113,1, 111,5, 110,7, 75,8, 42,8.

Example 547:

N-(2-Methylthiazole-4-ylethoxy)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 232)

General method 1, method 2.

Source materials: 2-[(quinoline-4-ylmethyl)amino]benzoic acid (see receiving IV) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (CDCl3) δ 168,9, 167,0, 150,9, 150,4, 149,4, 148,0, 144,1, 133,6, 130,3, 129,3, 127,4, 126,8, 126,5, 122,5, 118,8, 118,2, 115,7, 112,7, 112,1, 73,1, 43,8, 19,2.

Example 548:

N-Cyclopentyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 233)

General method 1, method 2.

Source materials: 2-[(quinoline-4-ylmethyl)amino]benzoic acid (see receiving IV) hydrochloride and O-cyclopentyl-methylhydroxylamine (see getting 66).

1H is the Mr (DMSO-d 6) δ 11,48 (user., 1H), 8,81 (d, 1H), 8,23 (d, 1H), of 8.06 (d, 1H), 7,98 (t, 1H), 7,79 (t, 1H), to 7.67 (t, 1H), 7,44 (d, 1H), 7,39 (d, 1H), 7,19 (t, 1H), 6,59 (d, 1H), 6,59 (t, 1H), equal to 4.97 (d, 2H), 3,76 (d, 2H), 2,19 (m, 1H), 1,72 (m, 2H), and 1.54 (m, 4H), of 1.30 (m, 2H)

Example 549:

2-[(Quinoline-4-ylmethyl)amino]-N-(tetrahydropyran-4-ylethoxy)benzamide (compound 234)

General method 1, method 2.

Source materials: 2-[(quinoline-4-ylmethyl)amino]benzoic acid (see receiving IV) and the hydrochloride of O-(tetrahydropyran-4-ylmethyl)hydroxylamine (see getting 92).

ES+: (M+H)+ = 392 (M+Na)+= 414.

Example 550:

N-(4-Cyano-2-methoxybenzyloxy)-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 235)

General procedure 1, method 1.

Source materials: 2-[(6-methoxypyridine-3-ylmethyl)amino]benzoic acid (see obtaining 1W) hydrochloride and 4-aminoacetyl-3-methoxybenzonitrile (see 45).

13C-NMR (DMSO-d6) δ 167,3, 162,7, 157,0, 148,4, 145,6, 138,5, 132,6, 130,2, 130,0, 128,0, 127,7, 124,4, 118,7, 114,6, 114,0, 113,0, 111,7, 111,5, 110,3, 70,9, 56,0, 53,0, 42,9.

Example 551:

N-Benzyloxy-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 236)

General procedure 1, method 1.

Source materials: 2-[(6-methoxypyridine-3-ylmethyl)amino]benzoic acid (see obtaining 1W) hydrochloride and O-benzylhydroxylamine (Aldrich).

13SAMR (DMSO-d 6) δ 167,2, 162,7, 148,4, 145,6, 138,5, 135,9, 132,5, 128,8, 128,2, 128,0, 127,7, 114,6, 113,2, 111,5, 110,3, 76,9, 53,0, 42,9.

Example 552:

N-(4-Cyanobenzyl)-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 237)

General procedure 1, method 1.

Source materials: 2-[(6-Methoxypyridine-3-ylmethyl)amino]benzoic acid (see obtaining 1W) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,5, 162,8, 148,5, 145,7, 141,9, 138,6, 132,7, 132,2, 129,2, 128,1, 127,8, 118,8, 114,7, 113,0, 111,7, 110,8, 110,4, 76,0, 56,0, 42,9, 18,6.

Example 553:

N-Benzyloxy-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 238)

General procedure 1, method 1.

Source materials: 2-[(thiazol-5-ylmethyl)amino]benzoic acid (see obtaining IX) hydrochloride and O-benzylhydroxylamine (Aldrich).

13C-NMR (DMSO-d6) δ 167,0, 153,5, 148,0, 140,9, 138,0, 135,9, 132,4, 128,8, 128,2, 128,0, 115,1, 113,5, 111,6, 76,8, 38,5.

Example 554:

N-(2,4-Dichloraniline)-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 239)

General procedure 1, method 1.

Source materials: 2-[(thiazol-5-ylmethyl)amino]benzoic acid (see getting 1X) and chloride 1-[(ammoniac)methyl]-2,4-dichlorobenzene (Bionet).

13C-NMR (DMSO-d6) δ 153,5, 147,9, 140,9, 138,0, 134,1, 133,7, 132,8, 132,6, 132,5, 128,7, 128,1, 127,3, 115,1, 113,3, 111,6, 72,9, 38,5.

Example 555:

N-(2-Methylthiazole-4-ylethoxy)-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 240)

Get the method similar to that described for an example 516.

The initial substance: 1-(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7E) and the hydrochloride of O-(2-methylthiazole-4-ylmethyl)hydroxylamine (see obtaining 12).

13C-NMR (DMSO-d6) δ 165,3, 156,0, 150,5, 148,0, 145,3, 132,5, 128,0, 118,9, 117,1, 25 115,2, 113,5, 111,3, 71,9, 18,6.

Example 556:

N-Benzyloxy-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 241)

Get the method similar to that described for an example 516.

The initial substance: 1-(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7E) and hydrochloride O-benzylhydroxylamine (Aldrich).

1H-NMR (DMSO-d6) to 11.56 δ (user., 1H), 11,35 (user., 1H), 11,25 (s, 1H), 7,71 (t, 1H), 7.5 to about 7.2 (m, 7H), 6,74 (d, 1H), 6,60 (t, 1H), 4.92 in (s, 2H), 4,17 (d, 2H)

Example 557:

N-Benzyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 242)

A General method 1A.

The initial substance: 1-(2-imidazol-1-retil)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7F) hydrochloride and O-benzylhydroxylamine (Aldrich).13C-NMR (DMSO-d6) δ 148,5, 137,4, 136,0, 132,7, 129,5, 128,9, 18,4, 128,3, 128,3, 128,1, 119,5, 114,7, 113,0, 111,2, 76,9, 45,3, 43,2.

Example 558:

N-Cyclopentyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 243)

A General method 1A.

The initial substance: 1-(2-imidazol-1-retil)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7F) hydrochloride and O-cyclopentanecarboxylate (see getting 66).

13C-NMR (DMSO-d6) δ 166,8, 148,4, 137,3, 132,5, 128,3, 127,9, 119,4, 114,6, 113,1, 111,0, 79,4, 45,1, 43,1, 37,6, 28,9, 24,9.

Example 559:

N-(4-Cyanobenzyl)-2-(1-pyridine-4-ylethylamine)benzamide (compound 244)

A General method 1A.

The initial substance: 1-(1-pyridine-4-retil)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7G) and the hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,5, 154,0, 149,7, 147,6, 141,8, 132,5, 132,2, 129,1, 128,0, 121,0, 118,7, 114,9, 112,7, 112,3, 110,7, 75,9, 50,6, 23,8.

Example 560:

2-{[2-(3-Methylurea)pyridine-4-ylmethyl)amino}-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 245)

A General method 1A.

Educt: 1-[4-(2,4-dioxo-4H-benzo[d][1,3]oxazin-1-ylmethyl)pyridine-2-yl]-3-metalmachine (see example 525, stage 1) and the hydrochloride of O-(tetrahydropyran-2-ylmethyl)hydroxylamine (see getting 93).

13C-NMR (DMSO-d6) δ 167,0, 155,3, 153,7, 151,2, 148,5, 146,6, 132,4, 128,0, 115,1, 114,7, 113,1, 111,4, 109,1 78,5, 74,7, 67,1, 45,3, 27,7, 25,8, 25,4, 22,5.

Example 561:

N-Cyclopentyloxy-2-{[2-(2-methoxyethylamine)pyridine-4-ylmethyl]amino}benzamide (compound 246)

Get the method similar to that described to obtain 541.

The initial substance: 1-(2-aminopyridine-4-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7b) and methoxyacetyl chloride, hydrochloride then O-cyclopentyl-methylhydroxylamine (see getting 66).

13C-NMR (DMSO-d6) δ 168,4, 166,9, 151,6, 151,4, 148,4, 148,0, 132,4, 128,0, 117,9, 114,7, 113,4, 111,4, 111,3, 79,4, 71,1, 58,5, 45,3, 37,6, 28,9, 24,9.

Example 562:

N-(4-Cyanobenzyl)-2-[(6-oxo-1,6-dihydropyridines-3-ylmethyl)amino]benzamide (compound 247)

A General method 1A.

The initial substance: 1-(6-oxo-1,6-dihydropyridines-3-ylmethyl)-1H-benzo[d][1,3]oxazin-2,4-dione (see getting 7H), and hydrochloride of O-(4-cyanobenzyl)hydroxylamine (see 10).

13C-NMR (DMSO-d6) δ 167,3, 161,9, 149,5, 148,3, 141,8, 141,2, 133,1, 132,6, 132,1, 129,1, 128,0, 123,8, 120,0, 118,6, 115,6, 114,6, 112,8, 111,5, 110,7, 75,8, 42,2.

Example 563:

N-Cyclopentyloxy-2-[(tetrahydropyran-4-ylmethyl)amino]benzamide (compound 248)

General method 1, method 2.

Source materials: 2-[(tetrahydropyran-4-ylmethyl)amino]benzoic acid (see getting 1Y) hydrochloride and O-cyclopentyl-metalhydroxide the ina (see getting 66).

13C-NMR (DMSO-d6) δ 167,2, 149,2, 132,6, 127,9, 113,9, 112,5, 111,1, 79,4, 66,7, 48,1, 37,6, 34,0, 30,5, 29,0, 24,9.

Example 564:

N-(3-Iodine-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 250)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,2, 140,6, 138,7, 135,6, 132,5, 129,6, 128,8, 128,0, 121,9, 114,8, 113,4, 111,4, 100,9, 75,5, 44,8, 27,1.

Example 565:

N-(4-Ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 251)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 149,8, 149,2, 148,4, 143,9, 133,3, 132,5, 129,1, 128,2, 127,7, 122,2, 114,9, 113,6, 111,5, 76,9, 44,9, 28,0, 15,6.

Example 566:

N-(4-Isopropylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 252)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 149,5, 149,0, 148,5, 148,3, 133,3, 132,4, 129,0, 128,0, 126,1, 122,0, 114,8, 113,5, 111,4, 76,8, 44,8, 33,1, 23,8.

Example 567:

N-(4-tert-Butylbenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 253)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 150,7, 149,5, 149,0, 148,3, 132,9, 132,4, 128,7, 128,0, 125,0, 122,0, 114,8, 113,5, 111,4, 76,7, 44,8, 34,2, 31,0.

Example 568:

N-(2-Ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (connect the tion 254).

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 151,7, 148,3, 148,0, 143,7, 133,1, 132,6, 130,7, 128,9, 128,5, 128,3, 125,7, 122,6, 115,0, 113,7, 111,6, 74,9, 45,0, 24,8, 15,7.

Example 569:

N-(2-Non-1-universilence)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 255)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 149,7, 149,1, 148,8, 138,6, 134,5, 133,5, 131,7, 131,1, 129,3, 127,3, 126,8, 126,4, 126.2, 122,0, 115,7, 112,8, 112,1, 76,3, 46,1, 33,4, 31,9, 29,4, 29,2, 29,2, 22,7, 14,1.

Example 570:

N-(4-Phenylenedimethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 256)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 149,5, 149,0, 148,5, 148,2, 140,4, 134,2, 132,4, 128,9, 128,7, 128,0, 126,9, 121,9, 115,6, 114,8, 113,4, 112,2, 111,4, 76,7, 46,1, 44,8.

Example 571:

N-(4-Diethylaminoethylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 257)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,7, 149,5, 149,0, 148,2, 140,1, 134,2, 132,3, 128,7, 128,3, 128,0, 121,9, 114,8, 113,4, 111,4, 76,7, 56,6, 46,1, 44,8, 11,6.

Example 572:

N-(2-Carbamoylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 258)

Get techniques that are similar to those described above for compounds 1-249.

1H-NMR (CD3 OD) δ 8,79 (m, 2H), 8,10 (m, 2H), 7,53 -7,21 (m, 6H), 6,70 (m, 1H), 6,53 (d, 1H), further 5.15 (s, 2H), to 4.87 (s, 2H), 3,93 (s, 2H).

Example 573:

N-[4-Cyano-2-(2-methoxyethoxy)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 259)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 156,3, 149,7, 149,1, 148,5, 132,7, 130,6, 130,1, 128,2, 35 124,7, 122,1, 118,8, 115,2, 114,9, 113,2, 111,6, 71,0, 70,2, 68,2, 58,3, 44,9.

Example 574:

N-(4-Cyanomethyl-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 260)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 157,5, 149,5, 149,0, 148,2, 132,9, 132,4, 130,9, 128,1, 123,3, 121,9, 119,7, 119,0, 114,7, 113,4, 111,4, 110,8, 71,1, 55,4, 44,7, 22,4.

Example 575:

N-(5-Cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 261)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 160,6, 149,5, 148,9, 148,3, 134,3, 133,4, 132,5, 128,0, 125,8, 121,9, 119,0, 114,8, 113,3, 111,9, 111,4, 102,4, 70,7, 56,0, 44,8.

Example 576:

2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}phenyl)carbamino acid tert-butyl ester (compound 262)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,4, 153,9, 149,8, 149,5, 148,9, 139,7, 133,9, 130,9, 130,4, 127,5, 122,9, 122,4, 121,8, 120,9, 115,7, 112,3, 111,6, 79,7, 768, 45,9, 28,4.

Example 577:

N-(2-Acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 263)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,3, 170,0, 149,9, 149,4, 148,3, 139,1, 134,2, 130,7, 130,4, 127,5, 123,6, 123,3, 122,7, 122,1, 116,0, 112,3, 111,5, 77,2, 46,2, 24,3.

Example 578:

N-(2-Benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 264)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 168,1, 166,4, 149,6, 148,9, 148,7, 138,0, 135,0, 133,1, 131,5, 130,6, 129,2, 128,1, 128,0, 127,2, 124,6, 124,1, 121,9, 115,0, 112,1, 111,8, 74,7, 44,7.

Example 579:

N-(2-Methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 265)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,7, 149,7, 149,5, 148,6, 138,7, 134,1, 131,3, 130,8, 127,5, 124,5, 124,2, 122,1, 121,5, 115,7, 112,3, 111,2, 76,8, 46,0, 40,1.

Example 580:

N-(4-Acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 266)

Get techniques that are similar to those described above for compounds 1-249.13C-NMR (DMSO-d6) δ 168,2, 167,0, 149,5, 149,0, 148,2, 139,3, 132,4, 130,2, 129,6, 10 128,0, 121,9, 118,5, 114,8, 113,5, 111,4, 76,5, 44,7, 23,9.

Example 581:

N-(Biphenyl-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 267)

Get methods, is the quiet similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 149,6, 149,0, 148,4, 140,0, 139,7, 135,1, 132,5, 129,5, 128,9, 128,1, 127,5, 126,6, 126,5, 122,0, 114,8, 113,5, 111,5, 76,6, 44,8.

Example 582:

N-[Biphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 268)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,7, 149,5, 148,8, 148,5, 142,8, 140,2, 133,1, 132,4, 130,7, 130,1, 129,2, 128,5, 128,0, 127,3, 127,2, 127,1, 121,7, 115,4, 112,6, 111,8, 76,0, 45,8.

Example 583:

N-(3'-Methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 269)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,8, 159,4, 149,3, 149,0, 142,9, 141,8, 133,4, 132,7, 130,9, 130,1, 129,2, 128,7, 127,6, 127,4, 122,1, 121,9, 118,9, 115,7, 115,1, 112,9, 112,7, 112,0, 76,3, 55,3, 46,0.

Example 584:

N-(2'-Methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 270)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,4, 156,5, 149,6, 148,9, 138,9, 134,2, 133,3, 131,0, 130,7, 129,6, 129,4, 129,1, 128,4, 127,7, 127,3, 122,0, 120,7, 115,6, 113,0, 111,9, 110,9, 76,3, 55,5, 46,0.

Example 585:

N-[3'-Hydroxymethyluracil-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 271)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 149,6, 149,0, 143,3, 140,9, 140,6, 133,3, 132,3, 131,7, 10 130,1, 129,0, 128,4, 128,4, 128,3 127,7, 127,6, 126,0, 122,0, 115,7, 112,8, 112,0, 76,8, 65,0, 46,0.

Example 586:

N-(3-Phenoxybenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 272)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,0, 157,4, 156,9, 149,6, 148,9, 137,7, 133,3, 129,9, 129,8, 127,8, 123,9, 123,4, 122,0, 119,4, 118,9, 115,6, 112,9, 111,9, 77,8, 46,0.

Example 587:

N-(Anthracene-9-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 273)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 149,5, 149,1, 148,4, 132,5, 131,0, 130,8, 128,8, 128,7, 128,2, 126,5, 126,2, 125,2, 124,5, 121,9, 114,8, 113,4, 111,5, 68,9, 44,8.

Example 588:

N-[4-(2-Methylthiazole-4-yl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 274)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 165,5, 153,4, 149,5, 148,9, 148,3, 135,4, 134,0, 132,5, 129,3, 128,0, 125,7, 121,9, 114,8, 113,9, 113,4, 111,4, 76,6, 44,8, 18,8.

Example 589:

N-(2-Methanesulfonamido-1 venlafaxi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 275)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 149,5, 148,9, 148,1, 137,8, 132,5, 128,3, 128,1, 127,4, 121,9, 114,8, 113,2, 111,4, 85,3, 46,4, 44,7, 39,6.

Example 590:

2-[(Pyridine-4-ylmethyl)amino]-N-[2-(4-triptoreline)thiazole-4-ylethoxy]benzamid connection 276)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 165.2, 152,7, 149,6, 149,0, 148,4, 136,4, 132,6, 130,0, 128,2, 126,8, 126.2, 123,9, 122,0, 121,4, 114,9, 113,4, 111,5, 71,9, 44,9.

Example 591:

2-[(Pyridine-4-ylmethyl)amino]-N-(3-para-tolerization-5-ylethoxy)benzamide (compound 277)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,8, 167,5, 161,7, 149,5, 148,9, 148,3, 139,9, 132,7, 129,6, 128,2, 126,4, 125,5, 121,9, 114,8, 112,9, 111,5, 103,2, 66,6, 44,8, 20,9.

Example 592:

N-(3-Methylisoxazol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 278)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 166,8, 159,6, 149,6, 149,0, 148,5, 132,8, 128,2, 122,0, 114,9, 113,1, 111,6, 105,8, 66,7, 44,9, 10,9.

Example 593:

N-(3-Utilization-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 279)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 166,7, 164,7, 149,5, 148,9, 148,4, 132,7, 128,1, 121,9, 114,8, 113,0, 111,5, 104,5, 66,7, 44,8, 18,8, 12,4.

Example 594:

N-(3-Butylisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 280)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 166,6, 163,5, 149,5, 148,9, 148,3, 32,7, 128,1, 121,9, 35 114,8, 113,0, 111,5, 104,8, 66,6, 44,8, 29,6, 24,8, 21,5, 13,4.

Example 595:

N-(3-Penilesecrets-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 281)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 166,6, 163,6, 149,5, 148,9, 148,4, 132,7, 128,1, 121,9, 114,8, 113,0, 111,5, 104,8, 66,6, 44,8, 30,6, 27,2, 25,1, 21,6, 13,7.

Example 596:

2-[(Pyridine-4-ylmethyl)amino]-N-[5-(3-triptoreline)-[1,2,4]oxadiazol-3-ylethoxy]benzamide (compound 282)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 174,1, 167,4, 166,7, 149,8, 149,5, 148,9, 148,4, 132,7, 131,8, 131,1, 129,8, 128,2, 124,2, 124,2, 123,4, 121,9, 114,8, 113,0, 111,5, 66,8, 44,8.

Example 597:

N-(1-Benzyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 283)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 149,6, 149,0, 148,4, 142,1, 136,1, 132,6, 128,7, 128,2, 128,1, 127,8, 125,4, 122,1, 114,9, 113,5, 111,5, 67,8, 52,8, 44,9.

Example 598:

N-(1-Cyclopentyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 284)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 149,6, 149,0, 148,4, 141,7, 132,6, 128,2, 123,8, 122,1, 114,9, 113,6, 111,5, 67,9, 61,0, 44,9, 32,9, 23,6.

Example 599:

N-(5-Oxo-4,5-dihydro-1H-[1,2,triazol-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 285)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 149,5, 148,9, 148,4, 137,4, 132,6, 129,3, 128,5, 128,1, 126,4, 122,0, 114,8, 113,2, 111,5, 70,8, 44,8.

Example 600:

N-(3-Phenoxypropane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 286)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,2, 158,8, 149,7, 149,1, 148,8, 133,4, 129,5, 127,5, 122,0, 120,8, 115,6, 114,5, 112,7, 112,0, 73,6, 64,5, 46,0, 28,3.

Example 601:

N-(3-Benzyloxy-propoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 287)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,8, 149,8, 149,1, 148,8, 138,2, 133,3, 128,5, 127,8, 127,8, 127,4, 122,0, 115,6, 112,8, 112,0, 74,2, 73,2, 67,4, 46,0, 28,7.

Example 602:

N-(2-Benzyloxyethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 288)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,5, 149,8, 149,2, 148,7, 137,7, 133,4, 128,6, 127,9, 127,3, 122,0, 115,7, 112,5, 112,0, 75,3, 73,6, 69,3, 46,0.

Example 603:

N-[2-Hydroxy-3-(4-methoxy-phenoxy)propoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 289)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 153,3, 152,5, 149,5, 148,9, 148,3, 132,5, 128,1, 121,9, 115,4, 114,8, 114,5, 113,1, 111,5, 77,1, 69,9, 66,8, 55,2 44,8

Example 604:

N-(3-Benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 290)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,3, 168,0, 149,8, 149,2, 148,8, 134,8, 133,5, 131,2, 128,2, 127,8, 127,4, 121,9, 115,7, 112,2, 112,1, 75,3, 45,9, 37,4, 27,5.

Example 605:

N-(4-Benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 291)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,2, 168,0, 149,7, 149,1, 148,9, 134,6, 133,3, 131,4, 128,5, 127,8, 127,0, 122,0, 115,7, 112,7, 111,9, 46,0, 39,6, 26,7, 25,3.

Example 606:

N-[2-Methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 292)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,6, 149,8, 149,3, 148,8, 134,0, 127,5, 122,0, 115,8, 112,3, 5 111,6, 75,9, 46,0, 41,6, 40,5.

Example 607:

N-(4-Benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 293)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,2, 149,6, 149,1, 140,1, 133,4, 132,4, 129,0, 127,7, 127,0, 122,1, 115,6, 112,6, 112,0, 76,3, 46,0, 42,9, 26,1, 25,6.

Example 608:

N-(3-Benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 294)

Get techniques that are similar to those described above glaswegians 1-249.

13C-NMR (CDCl3) δ 169,6, 149,7, 149,2, 148,8, 140,5, 133,7, 132,3, 129,0, 127,6, 127,0, 122,0, 115,7, 112,1, 112,0, 74,7, 46,0, 40,8, 27,6.

Example 609:

N-[2-(4-Cyanobenzenesulfonyl)ethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 295)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,9, 149,8, 149,3, 148,7, 144,6, 134,2, 132,8, 127,7, 127,5, 122,0, 117,4, 116,1, 115,8, 112,4, 111,3, 75,5, 45,9, 41,6.

Example 610:

N-[3-(4-Cyanobenzenesulfonyl)propoxy)-2-[(pyridine-4-ylmethyl)amino] benzamide (compound 296)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,9, 149,8, 149,2, 148,7, 145,1, 133,9, 132,8, 127,7, 127,6, 122,1, 117,5, 115,8, 112,2, 111,8, 75,0, 46,0, 41,1, 27,4.

Example 611:

N-(3-Phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 297)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,2, 149,6, 149,0, 148,5, 133,5, 130,5, 129,4, 128,4, 128,3, 127,3, 121,7, 115,5, 111,9, 111,8, 74,2, 58,9, 45,8, 40,8, 28,3.

Example 612:

N-(2-Phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 298)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,3, 149,9, 149,3, 148,6, 133,9, 130,8, 129,3, 128,7, 128,7, 127,4, 121,9, 115,8, 112,3, 111,7, 76,2, 59,7, 46,0, 42,0.

Example 613:

N-3-(2-Acetylamino-4-methylthiazole-5-sulfonylamino)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 299)

Get techniques that are similar to those described above for compounds 1-249.

1H-NMR (CD3OD) δ to 8.45 (d, 2H), 7,44 (d, 2H), 7,40 (d, 1H), 7.22 (dt, 1H), 6,60 (t, 1H), 6,55 (d, 1H), 4,55 (s, 2H), 4,01 (t, 2H), 3.20 (t, 2H), 2,50 (s, 3H), 2,17 (s, 3H), 1,89 (m, 2H).

Example 614:

N-(2-(2-Acetylamino-4-methylthiazole-5-sulfonylamino)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 300)

Get techniques that are similar to those described above for compounds 1-249.

1H-NMR (DMSO-d6) δ 12,48 (s, 1H), 11,57 (s, 1H), 8,49 (d, 2H), 7,87 (m, 2H), 7,38 (DD, 1H), 7,31 (d, 2H), 7,21 (dt, 1H), 6,55 (t, 1H), 6,51 (d, 1H), 4,47 (d, 2H), 3,92 (t, 2H), 25 of 3.15 (q, 2H), 2,46 (s, 3H), and 2.14 (s, 3H).

Example 615:

N-(2-Benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 301)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,4, 150,0, 149,0, 148,6, 138,9, 133,2, 128,6, 128,4, 127,7, 127,4, 122,0, 115,6, 112,7, 111,9, 74,6, 53,6, 47,9, 46,1.

Example 616:

N-(4-Benzylaminopurine)-2-[(pyridine-4-ylmethyl-amino]benzamide (compound 302)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,2, 150,0, 149,0, 148,6, 139,5, 133,1, 128,5, 128,2, 127,5, 127,2, 122,0, 115,6, 112,9, 111,9, 76,3, 53,8, 48,8, 46,1, 26,3, 25,3.

Example 617:

tert-Butyl ether (2-(2-[(pyridine-4-ylmethyl)amino]benzoylamino}ethyl) - carbamino acid (compound 303)

Get methods, is the quiet similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,0, 157,1, 149,8, 149,3, 148,8, 133,5, 127,4, 122,0, 115,8, 112,4, 112,1, 80,0, 75,3, 46,1, 38,5, 28,4.

Example 618:

tert-Butyl methyl ether (3-(2-[(pyridine-4-ylmethyl)amino]benzoylamino}propyl)carbamino acid (compound 304)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 156,6, 149,8, 149,3, 148,8, 133,4, 127,5, 122,0, 115,6, 112,5, 112,1, 79,4, 74,4, 46,0, 37,2, 28,7, 28,4.

Example 619:

tert-Butyl ester (4-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}butyl)carbamino acid (compound 305)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,0, 156,4, 149,8, 149,2, 148,8, 133,3, 127,7, 122,0, 115,6, 112,8, 111,9, 79,3, 76,9, 46,0, 40.2, 28,4, 27,4, 25,0.

Example 620:

N-[2-(3-Phenylthioureido)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 306)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 180,8, 169,9, 149,8, 149,3, 148,7, 136,4, 133,7, 129,8, 127,6, 126,8, 125,4, 122,0, 115,8, 112,1, 111,8, 74,8, 45,9, 43,6.

Example 621:

N-[4-(3-Phenylthioureido)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 307)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 180,9, 169,2, 149,7, 149,0, 148,8, 136,9, 133,6, 129,8, 127,6, 126,8, 125,0, 122,0, 115,8, 112,3, 112,1, 46,0, 45,0, 25,8.

Example 622:

N - [2-(3-Phenylurea)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 308)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 157,4, 149,8, 149,3, 148,7, 139,0, 133,7, 129,1, 127,8, 123,1, 122,0, 119,8, 116,1, 112,2, 112,0, 75,4, 46,0, 37,8.

Example 623:

N-[3-(3-Phenylurea)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 309)

Get techniques that are similar to those described above for compounds 1-249.13C-NMR (CDCI3) δ 169,2, 156,8, 149,7, 149,0, 148,9, 139,3, 133,5, 128,9, 128,0, 122,6, 122,0, 119,3, 115,9, 112,3, 112,0, 75,1, 45,9, 37,3, 28,0.

Example 624:

N-[4-(3-Phenylurea)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 310)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 156,7, 149,6, 149,1, 149,0, 139,6, 133,5, 128,9, 128,2, 122,3, 122,1, 119,0, 116,0, 112,5, 112,0, 76,8, 46,0, 39,7, 27,2, 26,1.

Example 625:

N-(2-Aminoethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 311)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 164,7, 149,5, 142,4, 134,9, 129,5, 126,5, 117,6, 113,9, 113,1, 73,8, 47,1, 39,2.

Example 626:

N-(3-Aminopropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 312)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 149,4, 149,2, 148,4, 132,7, 128,2, 122,0, 114,8, 112,8, 111,5, 73,2, 44,8, 36,8, 25,5.

Example 627:

N-(4-Aminobutoxy)-2-[(pyrid is n-4-ylmethyl)amino]benzamide (compound 312)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,6, 149,5, 149,2, 147,7, 130,9, 128,4, 122,0, 116.2, 114,6, 110,8, 73,9, 45,0, 40,5, 28,2, 25,6.

Example 628:

N-(2-Morpholine-4-yl-2-oksidoksi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 314)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 165,5, 149,5, 148,9, 148,3, 132,7, 128,2, 121,9, 114,8, 12,9, 111,5, 73,5, 66,0, 65,9, 45,1, 44,7, 41,5.

Example 629:

N-[(2-Methoxyphenylacetyl)methoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 315)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 168,1, 166,5, 149,5, 149,1, 148,7, 148,6, 133,0, 128,2, 126,6, 124,5, 122,0, 120,8, 120,3, 114,9, 112,1, 111,7, 111,2, 75,3, 55,7, 44,8.

Example 630:

N-tert-Butoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 316)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 168,6, 149,5, 148,9 ,148,1, 132,2, 128,3, 122,0, 114,8, 114,3, 111,3, 80,8, 44,8, 26,5.

Example 631:

N-Isobutoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 317)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 149,6, 149,1, 148,4, 132,5, 128,1, 122,1, 114,9, 113,6, 111,5, 81,7, 44,9, 27,0, 19,2.

Example 632:

N-(2-Methylallyl the si)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 318)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 149,6, 149,1, 148,3, 140,8, 132,5, 128,2, 122,1, 114,9, 114,5, 113,7, 111,5, 78,9, 44,9, 19,6.

Example 633:

N-(3-Methylbut-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 319)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 149,6, 149,1, 148,4, 139,3, 132,5, 128,1, 122,1, 118,9, 114,9, 113,7, 111,5, 71,2, 44,9, 25,5, 18,0.

Example 634:

N-(4-Hydroxyben-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 320)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,8, 149,5, 148,9, 148,3, 140,7, 132,3, 128,0, 122,2, 122,0, 114,8, 113,6, 111,4, 75,3, 65,8, 44,9, 23,5.

Example 635:

N-Cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 321)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,0, 148,2, 132,3, 128,0, 122,0, 114,8, 113,7, 111,4, 86,2, 44,8, 30,7, 23,3.

Example 636:

N-Cyclooctylamino-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 322)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,0, 148,2, 132,3, 128,0, 122,0, 114,8, 113,8, 111,4, 84,5, 44,8, 29,6, 26,7, 24,9, 22,6.

Example 637:

N-(2-Cyclohexylmethoxy)-2-[(feast of the DIN-4-ylmethyl)amino]benzamide (compound 323)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 149,6, 149,1, 148,4, 132,5, 128,1, 122,1, 114,9, 113,6, 111,5, 73,3, 44,9, 35,2, 34,0, 32,8, 26,1, 25,8.

Example 638:

N-(2-Methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 324)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,3, 128,0, 122,0, 114,8, 113,6, 111,4, 78,6, 44,8, 43,1, 35,1, 33,6, 29,7, 25,8, 25,6, 20,1.

Example 639:

N-(4-Methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 325)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,4, 80,7, 44,8, 36,1, 34,1, 32,1, 29,2, 22,5.

Example 640:

N-(4-Methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 326)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,9, 149,5, 149,0, 148,3, 132,4, 128,0, 122,0, 114,8, 113,5, 111,4, 80,0, 78,5, 54,8, 44,8, 35,7, 30,8, 27,1.

Example 641:

N-(3-Methylbicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 327)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 169,0, 149,8, 149,1, 148,8, 133,4, 127,3, 122,0, 115,7, 112,8, 112,1, 80,5, 78,6, 49,1, 8,3, 46,0, 43,2, 41,7, 41,2, 39,9, 39,1, 39,0, 37,5, 36,5, 30,0, 29,9, 22,0, 21,6, 16,4.

Example 642:

N-(Bicyclo[2.2.1]hept-5-ene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 328)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 149,5, 149,3, 148,4, 137,0, 136,6, 136,3, 132,5, 128,1, 122,1, 114,9, 111,6, 79,6, 78,8, 48,9, 44,9, 43,6, 43,3, 41,6, 41,1, 37,2, 37,0, 29,2, 28,8.

Example 643:

tert-Butyl ether benzyl-(2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}cyclohexyl)carbamino acid (compound 329)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 156,0, 149,6, 149,1, 149,1, 140,4, 133,5, 128,3, 127,4, 126,5, 126,2, 122,1, 115,7, 112,6, 112,1, 79,9, 75,8, 58,2, 46,1, 36,9, 28,4, 27,9, 26,4, 20,7.

Example 644:

N-(2-Benzylaminocyclohexanemethanol)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 330)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 149,6, 149,1, 148,3, 132,3, 128,4, 128,3, 128,1, 126,8, 122,0, 114,9, 113,9, 111,5, 76,1, 54,9, 50,0, 44,9, 37,1, 27,4, 25,4, 22,8, 22,2.

Example 645:

N-(3-Propyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 331)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,6, 158,9, 150,0, 149,4, 148,8, 133,0, 128,5, 122,4, 115,2, 113,6, 111,9, 77,0, 76,9, 45,2, 39,2 29,1, 19,5, 13,9.

Example 646:

N-(3-Pentyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 332)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 158,8, 149,6, 149,0, 148,5, 132,6, 128,2, 122,0, 114,9, 113,2, 111,6, 76,6, 76,5, 44,9, 38,8, 30,8, 26,8, 25,4, 21,8, 13,8.

Example 647:

4-Methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 333)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 165,3, 150,6, 149,6, 149,0, 148,7, 142,5, 128,1, 122,0, 118,8, 115,9, 111,7, 110,4, 71,9, 44,8, 21,4, 18,6.

Example 648:

N-(5-Cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 334)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,8, 160,7, 156,6, 151,2, 149,6, 149,3, 136,1, 134,5, 133,6, 125,6, 121,9, 119,0, 112,0, 111,1, 108,1, 102,4, 70,8, 56,0, 42,7.

Example 649:

2 Benzylamino-N-benzyloxyaniline (compound 335)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,8, 156,8, 151,2, 140,1, 136,0, 135,8, 128,8, 128,2, 127,1, 126,6, 110,7, 107,7, 76,9, 43,7.

Example 650:

2 Benzylamino-N-(4-methoxybenzyloxy)nicotinamide (compound 336)

Get techniques that are similar to those described above for soybeans is ineni 1-249.

13C-NMR (DMSO-d6) δ 165,7, 159,3, 156,8, 151,2, 140,1, 135,9, 130,6, 128,2, 127,7, 127,1, 126,6, 113,6, 110,7, 107,8, 76,6, 55,0, 43,7.

Example 651:

N-Benzyloxy-2-(2-chlorobenzylamino)nicotinamide (compound 337)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,7, 156,6, 151,2, 137,1, 136,0, 135,8, 132,2, 129,1, 128,8, 128,7, 128,3, 128,2, 127,0, 111,0, 108,1, 76,9, 41,7.

Example 652:

2-(2-Chlorobenzylamino)-N-(4-methoxybenzyloxy)nicotinamide (compound 338)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,7, 159,3, 156,6, 151,1, 137,2, 136,0, 132,2, 130,7, 129,1, 128,7, 128,3, 127,7, 127,0, 113,6, 111,0, 108,2, 76,6, 55,0, 41,8.

Example 653:

N-Benzyloxy-2-(2,4-dichloraniline)nicotinamide (compound 339)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,6, 156,4, 151,1, 136,5, 136,1, 135,8, 132,9, 131,8, 129,9, 128,8, 128,5, 128,2, 127,1, 111,2, 108,2, 76,9, 41,4.

Example 654:

2-(3,5-Dichloraniline)-N-(4-methoxybenzyloxy)nicotinamide (compound 340)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,6, 159,3, 156,5, 151,1, 136,5, 136,0, 132,9, 131,8, 130,7, 129,9, 128,5, 127,8, 127,1, 113,6, 111,2, 108,3, 76,6, 55,0, 41,4.

Example 655:

N-Benzyloxy-2-(2-methoxybenzylamine)nicotinamide (compound 341)

Get n the methods, which are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,8, 157,0, 151,3, 135,9, 135,8, 128,8, 128,2, 127,9, 127,8, 127,3, 120,0, 110,5, 107,7, 76,9, 55,2, 39,3.

Example 656:

2-(2-Methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 342)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,8, 159,3, 157,0, 151,2, 135,9, 130,6, 129,6, 127,9, 127,8, 127,3, 120,1, 113,6, 113,5, 110,5, 107,8, 76,6, 55,2, 55,0, 39,3.

Example 657:

N-Benzyloxy-2-(2-pyridin-4-ylethylamine)nicotinamide (compound 343)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 156,8, 151,3, 149,4, 148,6, 135,9, 128,8, 128,2, 124,1, 110,5, 107,7, 76,9, 40,6, 34,2.

Example 658:

N-(2-Bromobenzylamine)-2-([1,2,4]triazole-4-ylamino)nicotinamide (compound 344)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 155,0, 150,6, 144,5, 136,8, 135,0, 132,5, 131,2, 130,4, 127,8, 123,3, 115,7, 110,4, 76,1.

Example 659:

tert-Butyl ether 4-{[3-(4-Methoxybenzyloxy)pyridine-2-ylamino]methyl}piperidine-1 - carboxylic acid (compound 345)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 159,3, 157,1, 153,8, 151,2, 135,9, 130,6, 127,8, 113,6, 110,2, 107,5, 78,3, 76,5, 55,0, 45,5, 43,2, 35,3, 29,5, 28,0.

Example 660:

The N-5-[(2-benzyloxycarbonylamino)methyl]-2-perbenzoic (compound 346)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 161,2, 157,9, 148,4, 136,0, 135,7, 132,5, 131,0, 128,8, 128,2, 128,0, 121,5, 116,1, 114,6, 113,2, 111,5, 77,0, 76,9, 44,9.

Example 661:

N-(2-Bromobenzylamine)-2-(3-cyano-4-methoxybenzylamine)benzamide (compound 347)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 159,8, 148,3, 135,3, 133,8, 132,5, 132,4, 132,0, 131,1, 130,2, 128,1, 127,7, 123,1, 116,4, 114,7, 113,2, 112,4, 111,5, 100,0, 75,8, 56,2, 44,5.

Example 662:

N-(2-Bromobenzylamine)-2-(4-methanesulfonanilide)benzamide (compound 348)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 148,4, 146,1, 139,3, 135,3, 132,6, 132,4, 131,1, 130,2, 128,2, 127,7, 127,6, 127,1, 123,2, 114,7, 113,1, 111,5, 75,9, 45,4, 43,5

Example 663:

2-[4-(Methoxyaminomethyl)benzylamino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 349)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 165,3, 150,6, 148,5, 148,4, 141,6, 132,4, 130,5, 128,0, 127,3, 126,9, 118,8, 114,6, 113,0, 111,5, 71,8, 61,4, 45,7, 18,6.

Example 664:

N-(2-Bromobenzylamine)-2-[(2,6-dichloropyridine-4-ylmethyl)amino]benzamide (compound 350)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 153,0, 149,4, of 149.0, 38,7, 134,1, 132,4, 131,5, 130,6, 127,8, 127,8, 123,2, 123,0, 121,3, 116,0, 114,6, 76,0, 45,5.

Example 665:

N-Benzyloxy-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 351)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 149,2, 148,8, 148,5, 135,4, 134,9, 134,5, 133,5, 129,3, 128,8, 128,7, 127,4, 123,7, 115,6, 112,7, 112,0, 78,5, 44,7.

Example 666:

N-(2-Methylthiazole-4-ylethoxy)-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 352)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 166,9, 150,9, 149,2, 148,9, 148,5, 134,9, 134,5, 133,4, 127,6, 123,6, 118,3, 115,5, 112,8, 112,0, 73,0, 44,7, 19,1.

Example 667:

N-(2-Methylthiazole-4-ylethoxy)-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 353)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 166,9, 158,9, 151,0, 149,2, 136,8, 133,3, 127,7, 122,0, 121,1, 118,3, 115,3, 112,9, 112,2, 73,0, 48,8, 19,1.

Example 668:

N-Benzyloxy-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 354)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,9, 158,8, 149,1, 136,9, 135,6, 133,3, 129,3, 128,7, 128,6, 127,5, 122,0, 121,0, 115,4, 113,0, 112,3, 78,3, 48,7.

Example 669:

N-Benzyloxy-2-[(3-bromopyridin-2-ylmethyl)amino]benzamide (compound 355)

Get techniques that are similar to those described above on the I compounds 1-249.

13C-NMR (CDCl3) δ 161,0, 148,8, 141,6, 139,2, 135,5, 133,5, 129,3, 128,8, 128,7, 127,4, 126,4, 119,6, 115,8, 112,7, 112,3, 78,4, 48,5.

Example 670:

2-[(3-Bromopyridin-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 356)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,8, 167,0, 161,1, 150,8, 149,0, 141,6, 139,2, 133,4, 127,6, 126,3, 119,6, 118,3, 115,7, 112,8, 112,1, 72,9, 48,4, 19,0.

Example 671:

N-(2,4-Dichloraniline)-2-[(2,6-dimethoxypyrimidine-4-ylmethyl)amino]benzamide (compound 357)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 168,7, 167,3, 164.2, 156,9, 148,3, 134,1, 133,7, 132,8, 132,6, 128,7, 128,1, 127,3, 114,8, 113,3, 111,9, 111,4, 72,9, 54,3, 53,8, 38,3.

Example 672:

N-Benzyloxy-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 358)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 162,2, 148,9, 144,4, 136,9, 135,8, 132,7, 128,7, 128,2, 127,8, 114,2, 112,5, 111,3, 76,8, 36,4, 35,5, 11,4, 9,0.

Example 673:

N-(2,4-Dichlorobenzyl)-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 359)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 162,2, 148,8, 144,4, 136,8, 134,0, 133,6, 132,7, 132,5, 128,6, 127,9, 127,3, 114,2, 112,4, 112,2, 111,3, 72,9, 36,4, 35,5, 11,4, 9,0.

Example 674:

N-Benzylic and-2-[(1-methyl-1H-imidazol-2-ylmethyl)amino]benzamide (compound 360)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 148,6, 144,9, 135,7, 133,3, 129,3, 128,7, 128,6, 127,6, 126,7, 121,8, 116,0, 113,4, 112,5, 78,2, 40,4, 33,0.

Example 675:

2-[(1-Methyl-1H-imidazol-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 361)

Get techniques that are similar to those described above for compounds 1-249.

1H-NMR (CD3OD) δ 7,46 (s, 1H), was 7.36 (DD, 1H), 7,29 (dt, 1H), was 7.08 (s, 1H), 6,94 (s, 1H), 6,85 (d, 1H), 6,63 (t, 1H), 4,99 (s, 2H), 4.53-in (s, 2H, in), 3.75 (s, 3H), 2,69 (s, 3H).

Example 676:

N-Benzyloxy-2-[(3-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 362)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 148,4, 138,5, 135,9, 132,5, 128,8, 128,6, 128,2, 127,9, 127,5, 114,8, 113,0, 111,6, 76,8, 36,1, 30,9.

Example 677:

2-[(3-Methyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 363)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 165,3, 150,5, 148,4, 138,5, 132,5, 128,6, 128,0, 127,5, 118,9, 114,8, 113,1, 111,6, 71,8, 36,1, 30,9, 18,6.

Example 678:

N-Benzyloxy-2-[(5-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 364)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 148,7, 136,0, 133,2, 132,5, 130,4, 128,7, 128,2, 128,1, 17,8, 124,4, 114,1, 112,6, 111,3, 76,8, 38,8, 9,7.

Example 679:

2-[(5-Methyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methyl-thiazole-4-ylethoxy)benzamide (compound 365)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 168,5, 166,7, 150,8, 148,8, 133,5, 133,1, 129,2, 128,2, 126.2, 118,4, 115,2, 113,2, 111,6, 72,7, 39,0, 18,9, 10,0.

Example 680:

2-[(2-Ethyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 366)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CD3OD) δ 170,1, 168,8, 152,0, 151,4, 150,2, 136,1, 134,2, 129,2, 120,4, 5 117,0, 116,4, 114,5, 112,9, 73,4, 40,9, 22,3, 18,7, 13,0.

Example 681:

N-Benzyloxy-2-[(2-ethyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 367)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CD3OD) δ 170,1, 151,5, 150,3, 137,2, 136,5, 134,1, 130,5, 129,6, 129,5, 129,1, 117,1, 116,3, 114,6, 112,9, 79,2, 41,2, 22,5, 13,2.

Example 682:

N-(2,5-Dichloraniline)-2-[(5-oxopyrrolidin-2-ylmethyl)amino]benzamide (compound 368)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 176,7, 167,6, 149,1, 134,2, 133,8, 133,0, 132,8, 128,8, 128,7, 128,2, 127,4, 114,5, 112,7, 111,2, 73,1, 52,5, 46,8, 29,6, 24,2.

Example 683:

N-Benzyloxy-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 369)

Get method is the IKI, which are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 159,9, 148,9, 135,9, 132,6, 128,8, 128,2, 128,0, 114,5, 112,9, 111,3, 77,5, 76,9, 45,8, 20,5, 10,6.

Example 684:

N-Benzyloxy-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 370)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,2, 158,7, 148,9, 135,9, 132,6, 128,8, 128,2, 128,0, 114,5, 112,9, 111,3, 77,4, 76,9, 45,7, 28,8, 19,0, 13,5.

Example 685:

Ethyl ester 5-[(2-benzyloxycarbonylamino)methyl)-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 371)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,1, 155,5, 148,9, 135,9, 132,5, 128,8, 128,2, 127,9, 114,9, 113,2, 111,8, 87,0, 76,8, 61,3, 47.2, 45,0, 13,8, 12,3.

Example 686:

Ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 372)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,1, 159,9, 148,9, 135,9, 132,5, 128,8, 128,2, 127,9, 114,9, 113,1, 111,7, 86,8, 76,8, 61,4, 47,1, 43,3, 20,2, 13,8, 10,5.

Example 687:

Ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 373)

Get techniques that are similar to those described above is La compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,1, 158,7, 148,9, 135,9, 132,5, 128,8, 128,2, 127,9, 114,9, 113,1, 111,7, 86,7, 76,8, 61,4, 46,9, 43,3, 28,4, 18,9, 13,8, 13,3.

Example 688:

N-(4-Cyanobenzyl)-2-[(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 374)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 155,6, 148,9, 141,8, 132,7, 132,1, 129,1, 127,9, 118,7, 114,5, 112,5, 111,3, 110,7, 77,7, 75,9, 45,8, 41,4, 12,6.

Example 689:

N-(4-Cyanobenzyl)-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 375)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 159,9, 148,9, 141,8, 132,8, 132,2, 129,1, 128,0, 118,7, 114,5, 112,6, 111,3, 110,7, 77,5, 75,9, 45,8, 20,5, 10,6.

Example 690:

N-(4-Cyanobenzyl)-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 376)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 158,8, 148,9, 141,8, 132,7, 132,2, 129,1, 128,0, 118,7, 114,5, 111,3, 110,7, 77,4, 75,9, 45,7, 28,8, 19,0, 13,5.

Example 691:

Ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 377)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,3, 155,6, 148,9, 141,9, 132,6, 132,2, 129,1, 127,9, 118,7 115,0, 112,8, 111,8, 110,7, 87,0, 75,8, 61,3, 47,2, 45,0, 13,7, 12,3.

Example 692:

Ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 378)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,4, 159,9, 148,9, 141,8, 132,6, 132,2, 129,1, 127,9, 118,7, 114,9, 112,8, 111,8, 110,7, 86,8, 75,9, 61,3, 47,1, 43,3, 20,2, 13,8, 10,4.

Example 693:

Ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 379)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,5, 167,4, 158,7, 148,9, 141,8, 132,6, 132,2, 129,1, 127,9, 118,6, 114,9, 112,8, 111,7, 110,7, 86,7, 75,9, 61,3, 46,9, 43,3, 28,4, 18,9, 13,7, 13,3.

Example 694:

N-(4-Cyanobenzyl)-2-[(3-methylisoxazol-5-ylmethyl)amino]benzamide (compound 380)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,3, 167,3, 159,4, 148,1, 141,8, 132,7, 132,2, 129,1, 128,0, 118,7, 115,2, 113,3, 111,5, 110,8, 102,6, 75,9, 38,1, 10,8.

Example 695:

N-(4-Cyanobenzyl)-2-[(3-utilization-5-ylmethyl)amino]benzamide (compound 381)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,3, 167,2, 164,6, 148,1, 141,8, 132,7, 132,2, 129,1, 128,0, 118,6, 115,2, 113,2, 111,4, 110,8, 101,3, 75,9, 38,, 18,8, 12,3.

Example 696:

N-(4-Cyanobenzyl)-2-[(3-propylenoxide-5-ylmethyl)amino]benzamide (compound 382)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 170,2, 167,3, 163,3, 148,1, 141,8, 132,7, 132,2, 129,1, 128,0, 118,7, 115,2, 113,2, 111,5, 110,8, 101,6, 75,9, 38,2, 27,1, 20,9, 13,4.

Example 697:

N-(4-Cyanobenzyl)-2-[(3,5-dimethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 383)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 155,5, 149,3, 141,9, 132,6, 132,2, 129,1, 127,9, 118,7, 114,4, 112,4, 111,5, 110,7, 84,9, 75,8, 49,5, 46,8, 23,4, 12,9.

Example 698:

N-(4-Cyanobenzyl)-2-[(3-ethyl-5-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 384)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 159,9, 149,3, 141,8, 132,7, 132,1, 129,0, 127,9, 118,6, 114,4, 112,4, 111,4, 110,7, 84,6, 75,8, 49,5, 45,0, 23,3, 20,7, 10,6.

Example 699:

N-(4-Cyanobenzyl)-2-[(5-methyl-3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 385)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,5, 158,8, 149,4, 141,8, 132,7, 132,1, 129,1, 127,9, 118,7, 114,4, 112,4, 111,5, 110,7, 84,6, 75,9, 49,4, 45,1, 29,0, 23,4, 19,0, 13,4.

The example 700:

N-Benzyloxy-2-[(3-methyl-4,5-dihydroisoxazole-5-ilma who yl)amino]benzamide (compound 386)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 155,7, 149,0, 136,0, 132,7, 128,9, 128,3, 128,0, 114,6, 113,0, 111,4, 77,8, 77,0, 45,9, 41,5, 12,7.

Example 701:

N-(4-Cyanobenzyl)-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 387)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 155,5, 148,8, 141,9, 132,7, 132,1, 129,1, 128,0, 118,7, 114,2, 112,3, 111,0, 110,7, 77,4, 75,8, 43,3, 38,9, 34,2, 12,7.

Example 702:

N-Cyclopentyloxy-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 388)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 155,4, 148,9, 132,6, 127,9, 114,2, 112,8, 110,9, 79,4, 77,4, 43,3, 38,8, 37,6, 34,2, 29,0, 24,9, 12,7.

Example 703:

N-(4-Cyanobenzyl)-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 389)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 159,9, 148,8, 141,9, 132,7, 132,2, 129,1, 128,0, 118,7, 114,2, 112,3, 111,0, 110,7, 77,2, 75,8, 41,6, 38,9, 34,1, 20,6, 10,7.

Example 704:

N-Cyclopentyloxy-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 390)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 59,9, 148,9, 132,6, 128,0, 114,2, 112,8, 110,9, 79,4, 77,2, 41,6, 38,9, 37,6, 34,1, 29,0, 24,9, 20,6, 10,7.

Example 705:

N-(4-Cyanobenzyl)-2-[2-(3-propyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 391)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 158,7, 148,8, 142,0, 132,7, 132,2, 129,1, 128,0, 118,7, 114,2, 112,3, 111,0, 110,7, 77,1, 75,8, 41,6, 38,9, 34,2, 28,9, 19,1, 13,5.

Example 706:

N-Cyclopentyloxy-2-[2-(3-propyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 392)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 158,7, 149,0, 132,6, 128,0, 114,2, 112,8, 110,9, 79,4, 77,2, 41,6, 38,9, 37,7, 34,2, 29,0, 28,9, 25,0, 19,1, 13,5.

Example 707:

N-Benzyloxy-2-(2-(2,4-dioxoimidazolidin-1-yl)ethylamino]benzamide (compound 393)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 171,9, 167,2, 157,0, 148,7, 136,0, 132,7, 128,9, 128,3, 128,2, 114,6, 113,3, 111,1, 76,9, 51,0, 40,9, 40,3.

Example 709:

N-Benzyloxy-2-[(6-chloroimidazo[2,l-b]thiazole-5-ylmethyl)amino]benzamide (compound 395)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 166,8, 147,5, 146,1, 135,8, 132,3, 130,3, 128,8, 128,2, 128,1, 119,1, 118,9, 115,2, 114,1, 113,5, 111,2, 76,9, 35,5.

Example 710:

N-Benzyloxy-2-[(2-methylimidazo[1,2-a]pyrimidine-3-ylmethyl)and the eno]benzamide (compound 396)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 148, 7mm, 146,9, 146,9, 142.2, 135,8, 132,6, 132,4, 128,7, 128,2, 128,0, 115,6, 115,0, 111,7, 108,0, 76,8, 35,2, 13,4.

Example 711:

N-Benzyloxy-2-(2-benzyloxyaniline)benzamide (compound 397)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,3, 149,0, 138,3, 135,9, 132,6, 128,8, 128,2, 128,1, 127,9, 127,4, 127,3, 114,2, 112,8, 111,1, 76,9, 71,8, 68,0, 42,0.

Example 712:

N-(2-Benzyloxycarbonyl)isonicotinamide (compound 398)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 165,8, 162,9, 150,7, 141,3, 138,1, 135,6, 132,3, 128,9, 128,3, 128,2, 128,0, 123,8, 121,4, 120,8, 120,1, 77,0.

Example 713:

N-Benzyloxy-2-(2-pyridin-4-ylacetamide)benzamide (compound 399)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 167,9, 149,7, 143,8, 139,2, 135,1, 133,1, 129,3, 129,0, 128,7, 126,8, 124,7, 123,2, 121,5, 117,8, 78,4, 44,5.

Example 714:

N-Benzyloxy-N-methyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 400)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (CDCl3) δ 170,5, 149,9, 148,8, 147,0, 134,3, 131,9, 129,9, 129,6, 128,9, 128,6, 122,0, 117,2, 116,1, 111,6, 76,4, 46,3, 36,0.

Example 715:

N-(5-Oxopyrrolidin-2-ylethoxy)2-[(pyridine-4-ylmethyl)amino]benzamide (compound 402)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 176,7, 167,4, 149,7, 149,1, 148,4, 132,7, 128,2, 122,1, 114,9, 113,1, 111,6, 78,4, 51,7, 44,9, 29,4, 22,8.

Example 716:

tert-Butyl ether 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}piperidine-1-carboxylic acid (compound 403)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,1, 153,8, 149,5, 149,0, 148,4, 132,4, 128,1, 122,0, 114,8, 113,4, 111,5, 79,6, 78,4, 44,8, 37,5, 34,5, 28,3, 28,0.

Example 717:

N-Cyclopentyloxy-2-{[6-(cyclopropanecarbonyl)pyridine-3-ylmethyl]amino}benzamide (compound 404)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 172,4, 166,9, 151,1, 148,4, 146,7, 137,1, 132,4, 130,0, 127,9, 114,7, 113,4, 113,1, 111,5, 79,4, 43,1, 37,6, 28,9, 24,9, 14,0, 7,5.

Example 718:

N-Cyclopentyloxy-2-[(6-pyrrolidin-1-espiridion-3-ylmethyl)amino]benzamide (compound 405)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 156,3, 148,6, 147,1, 136,6, 132,4, 127,8, 121,1, 114,4, 113,0, 111,5, 106,1, 79,4, 46,3, 43,4, 37,6, 28,9, 24,9.

Example 719:

2-[(6-Aminopyridine-3-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 406)

Get techniques that are similar to those described above for compounds 1-249.13C-NMR (who MCO-d 6) δ 167,4, 159,0, 148,6, 146,9, 141,8, 136,7, 132,6, 132,1, 129,1, 127,9, 121,8, 118,7, 114,4, 112,5, 111,5, 110,7, 107,8, 75,8, 43,4.

Example 720;

N-(4-Cyanobenzyl)-2-[(6-pyrrolidin-1-espiridion-3-ylmethyl)amino]benzamide (compound 407)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,4, 156,3, 148,6, 147,1, 141,8, 136,6, 132,1, 132,0, 129,1, 127,9, 121,0, 118,7, 114,4, 112,6, 111,6, 110,7, 106,1, 75,8, 46,3, 43,4, 24,9.

Example 721:

N-Cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)-4-methylthiazole-5-ylmethyl]amino}benzamide (compound 408)

Get techniques that are similar to those described above for compounds 1-249.

Installed features13C and1H-NMR fully consistent with the structure.

Example 722:

2-[(6-Aminopyridine-3-ylmethyl)amino]-N-Cyclopentasiloxane (compound 409)

Get techniques that are similar to those described above for compounds 1-249.

13C-NMR (DMSO-d6) δ 167,0, 159,0, 148,6, 146,8, 136,7, 132,4, 127,8, 121,9, 114,4, 25 113,0, 111,5, 107,7, 79,4, 43,4, 37,6, 28,9, 24,9.

Example 723:

N-[3-(2,2-Dibromovinyl)cyclopentyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 410)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 724:

N-(3-Hydroximate is cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 411)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 725:

N-(2-Hydroxyethylacrylate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 412)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 726:

N-[4-(4-Methylpiperazin-1-ylmethyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 413)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 727:

N-(4-[4-(2-Hydroxyethyl)piperazine-1-ylmethyl]benzyloxy}-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 414)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 728:

N-(4-Cyanobenzyl)-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (compound 415)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully is clearly consistent with the structure.

Example 729:

N-(4-Cyanobenzyl)-2-{[2-(3-ethylurea)pyridine-4-ylmethyl)amino}benzamide (compound 416)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 730:

N-Cyclopentyloxy-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (compound 417)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 731:

N-Cyclopentyloxy-2-{[2-(3-propylurea)pyridine-4-ylmethyl)amino}benzamide (compound 418)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 732:

N-Cyclopentyloxy-2-{[2-(3-ethylurea)pyridine-4-ylmethyl]amino}benzamide (compound 419)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 733:

N-(3-Hydroxycyclopent)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 420)

Get techniques that are similar to opican the m above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 734:

N-Cyclopentyloxy-2-{[2-(3-methylthiourea)pyridine-4-ylmethyl]amino}benzamide (compound 421)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 735:

2-{[2-(3-tert-Butylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 422)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 736:

N-(4-Cyanobenzyl)-2-{[2-(3-cyclohexylurea)pyridine-4-ylmethyl]amino}benzamide (compound 423)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 737:

2-{[2-(3-Cyclohexylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 424)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 738:

N-{4-[(2-Cyclopentyloxy is ilfenomeno)methyl]pyridine-2-yl}isonicotinamide (compound 425)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 739:

{4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide 1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid (compound 426)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 740:

(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)amide 1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid (compound 427)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 741:

{4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide 1-acetylpiperidine-4-carboxylic acid (compound 428)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 742:

(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)amide 1-acetylpiperidine-4-carboxylic acid (compound 429)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 743:

N-Cyclopentyloxy-2-[(2,4-dihydroxypyrimidine-5-ylmethyl)amino]benzamide (compound 430)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 744:

(4-{[2-(4-Cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)amide, pyrrolidin-2-carboxylic acid (compound 431)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 745:

{4-[(2-Cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide pyrrolidin-2-carboxylic acid (compound 432)

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 746:

2-[(Pyridine-4-ylmethyl)amino]-N-(4-vinylbenzoate)benzamide (compound 433).

Get techniques that are similar to those described above for compounds 1-249. Installed features13C and1H-NMR fully consistent with the structure.

Example 36:

In vitro study of KDR kinase

In in vitro KDR-study using intracellular domain of the receptor KDR. This domain contains tyrosinekinase domain of KDR, and expression in Sf9 cells this domain is constitutively active, that is, the domain kinase fosfauriliruetsa on tyrosinosis residues. The substrate is a two domain PLCγ SH2, which is sufficient, as shown, for physiological interaction with the PDGF-R (Ji, Q.s., Chattopadhyay, A., Vecchi, M., and Carpenter, G. Mol.Cell.Biol., 19: 4961-4970, 1999) and TrkA (Angeles, T.S., Steffler, C, Bartlett, B.A., Hudkins, R.L, Stephens, R., Kaplan, D.R. and Dionne, C.A. Anal Biochem, 236: 49-55, 1996).

Biological materials:

Antibodies against PLCyl (530) (sc-426), Flk-1/KDR (C-20) (sc-315), GST (B-14) (sc-35 138) gain from Santa Cruz Biotechnology Inc., Santa-Cruz-Europe, Heidelberg, Germany. Anti-phospho-tyrosine (4G10) (No. cat. 05-321) from Upstate Biotechnology. Anti-phospho-tyrosine (PY20) (No. cat. P11120) from Transduction Laboratories, BD Biosciences, Franklin Lakes, NJ, USA. Labeled with europium PY20 anti-phosphotyrosine antibody from Wallac, Finland. Glutationreductaza 4B (No. cat. 17-0756-01), the detection reagent for Western blotting (No. cat), ECL Hyperfilm (no cat. RPN 3103H), protein molecular rainbow markers, 14,3-220 kDa (No. cat. RPN 756), column PD-10, γ-32P-ATP (No. cat. AA0068 250 µci/ml), the vector PGEX-4T-1 and cells of E. Coli BL21 (no cat. 27-1542-01) acquire from Amersham-Pharmacia Biotech, Europe, Denmark. Pefabloc (no cat. 1429868), Leupeptin (no cat. 1017101), Aprotinin (no cat. 236624) from Roche Molecular Biochemical Hvidovre, Denmark. Secondary antibodies from DAKO, Glostrup, Denmark. Biotin-marker (no cat. 7726L) from Cell Signaling Technologies Inc.,Beverly, MA, USA. Skim milk (MILEX®240) from Arla (the developer of MD Foods, Viby, Denmark. Nitrocellulose membrane 0.2 μm (No. cat. A010A304C) from Advantec MFC. 3 mm batmanesque filters (no cat. 3030917) from Whatmann International, England. TRIzol™, set for TA-cloning system GATEWAY Entry vector pDONR201 vector pDEST20, the system Bac-to-Bac, the vector pCR-3,1-Uni, pCR-Blunt II-TOPO, set to clone Zero Blunt TOPO, cell line Sf9, augmented environment of Grace for the cultivation of insect cells and CELLFECTIN from Invitrogen, Carlsbad, CA, USA. DMSO (D-2650), glutathione (G-4251), lysozyme (1-6876) and 10×PBS acquire from Sigma, Vallensbaek Str. Denmark. Chemicals for various buffers from Merck KGaA, Darmstadt, Germany. Black tablet for micrometrology on MaxiSorp 96 wells from NUNC, Denmark.

RT-PCR cloning of human KDR:

Allocate the whole RNA from endothelial cells of the umbilical vein of a person (HUVE)using the reagent TRIzol™ according to the manufacturer's instructions. Two μg total RNA is subjected to reverse transcription on the first chain cDNA using oligo(dT)16as a primer. This was followed by PCR amplification of the first chain cDNA encoding the complete coding region of human KDR, using the oligonucleotides 5'-TCTAGACAGGCGCTGGGA-GAAAGA-3' and 5'-TGCTGGTGGAAAGAACAA-CACTTCA-3'. Model oligonucleotides based on DNA sequences from GenBank inv. No. X89776 and X61656. PCR product clone to the age of the ora expression PCR-3,1-Uni, using the set for TA-cloning according to the manufacturer's instructions. Plasmid denote pMWM-78.

Construction of baculovirus bacmid KDR-cyt:

PCR amplification of cDNA encoding the intracellular part of KDR (KDR-cyt), which includes the kinase domain (nucleotide 2683-4455, transcription start +1), using oligonucleotides 5'-GGGGACAAGTTTGTACAAAAAAGCAGGCTCCGGAG-GGGAACTGAAGACGGGCTACT-3' and 5'-GGGGACCACTTTGTACAAGA-AAGCTGGGTATTTGCTGGTGGAAAGAACAACACTT-3'. Both of the oligonucleotide containing attB recombination sequences (underlined) for further cloning system GATEWAY. PCR product subcloning to the Entry vector pDONR201 using the GATEWAY system according to the manufacturer's instructions. The sequence identity is checked by DNA sequencing. Then transferred cDNA encoding a KDR-cyt, with pDORN201 on vector pDEST20, thus placing KDR-cyt in the cluster for the expression of the insect cells fused protein GST-KDR-cyt under control polietilenovogo promoter. GST-KDR-cyt transferred into a baculovirus bacmid using the Bac-to-Bac according to the manufacturer's instructions. In short, pDEST20/KDR-cyt transform E. coli DhlOBac, where it recombines into molecules with bactidol bMON 14272. Nekombinirovannyh bacmid purified from E. coli using preparative chromatography on a mini-column.

The Sf9 cells:

Cell line Sf9, pupae originating from ovarian tissue husinec owls and Spodoptera frugiperda, grow in an environment of Grace for the cultivation of insect cells, supplemented with 10% fetal calf serum (FCS), 100 U/ml penicillin and 100 mg/ml streptomycin, at 27°C. the Cell line passedout merging and usually diluted 1:6. Cells are removed by scraper.

Obtaining GST-KDR-cyt baculovirus in Sf9 cells:

Baculovirus bacmid containing gene-expression cluster GST-KDR-cyt, is transferred into the cells of the insect Sf9, applying mediated by liposomes CELLFECTIN transfection according to the manufacturer's instructions. Wednesday harvested three days after transfection and clarify by centrifugation (500×g, 5 min, 4°C) and the supernatant containing baculovirus particles, stored at 4°C for a short period of time or at 80°C for long term.

Amplification of recombinant baculovirus:

For amplification of the virus cells Sf9 from subconfluent culture were seeded into a flask for culturing T-80 with a density of 1x105cells/cm2and leave for adhesion for 45-60 min at 27°C. the Medium is sucked off from the monolayer and add 300 ál of viral raw materials from first getting together with 1700 ál of supplemented medium Grace for the cultivation of insect cells (without antibiotics and without FCS). Cells are incubated for 1 hour at 27°C before adding 15 ml of supplemented medium Grace for the cultivation of insect cells (100 U/ml penicillin, 100 mg/m is streptomycin and 10% FCS). After an incubation period of 72 hours, the supernatant containing baculovirus, collect, as described above.

Obtaining GST-KDR-cyt fused protein:

For purification of GST associated with KDR-cyt of cells, Sf-9, two flasks for culturing T-175 inoculated with cells from subconfluent culture with a density of 1x105cells/cm2. Cells leave for adhesion at 27°C for 45-60 minutes Culture medium is removed and cells infect the optimal amount of virus in 20 ml of supplemented medium Grace for the cultivation of insect cells (without antibiotics and without FCS). After 60 min incubation period at 27°C add 17 ml of supplemented medium Grace for the cultivation of insect cells (10% FCS, 100 U/ml penicillin and 100 mg/ml streptomycin) and collect the cells at the optimal time point after infection. Cells soskrebajut in a nutrient medium in a flask for their cultivation, transfer cells and medium in test tubes and centrifuged (500×g, 5 min, 4°C). The supernatant is sucked off and washed sediment into a chilled on ice physiological solution with phosphate buffer (PBS), 2x5 ml of Conduct lysis of the cells in 4 ml of the following buffer for lysis, which is obtained immediately before use: 50 mm HEPES pH 7.5, 150 mm NaCl, 10 mm EDTA, 10 mm Na4PO7, 100 mm NaF, 500 μm Pefabloc, 10 μg/ml Aprotinin, 10 μg/μl Leupeptin, 2 mm Na3VO4and 1% Triton X-100. The sample is incubated in the IDU for 10 min, then centrifuged (10000×g, 10 min, 4°C) and transfer the supernatant to a new centrifuge tube.

Purification of fused protein GST-KDR-cyt:

Get beads glutathione-sepharose by washing 3 times with 400 μl of beads HNT-buffer containing 30 mm HEPES pH 7.5, 30 mm NaCl and 0.1% Triton X-100, and then double-rinsing in buffer for lysis (50 mm HEPES pH 7.5, 150 mm NaCl, 10 mm EDTA, 10 mm Na4PO7, 100 mm NaF, 500 μm Pefabloc, 10 μg/ml Aprotinin, 10 μg/μl Leupeptin, 2 mm Na3VO4and 1% Triton X-100. Then add to the glutathione beads-sepharose 4000 ál of supernatant from lysed cells and leave the sample for 2 h to rotate slowly at 4°C, after which his centrifuged (1000×g, 30 sec, 4°C) and remove the supernatant.

For elution of proteins add 400 ál of 50 mm Tris/HCl pH 8.0 and 20 mm glutathione to the sample, incubated for 20 min, rotating at 4°C. the Sample is centrifuged (1000×g, 30 sec, 4°C) and collect the supernatant. This procedure is repeated 4 times or until until no longer buyouts protein is determined by measuring the absorbance at 280 nm (A280). GST-KDR-cyt absoluut and buffer glutathione/Tris change in TBS buffer (150 mm NaCl, 10 mm Tris/HCl pH 7.5)using a PD10 column. PD10 column contains Sephadex G-25 M. in Short, add GST-KDR-cyt eluate column PD-10 and elute 2.5 ml TBS buffer. GST-KDR-cyt eluate in TBS-buffer is measured by A280determine the amount of protein, and is but using BSA standard. Purified GST-protein analyzed by SDS-PAGE with subsequent Coomasie-staining and Western blot testing.

RT-PCT cloning PLCγ cDNA person:

Allocate the whole RNA from human embryonic kidney HEK293 cells using the TRIzol reagent™. Reverse transcription of two µg of total RNA on the first chain cDNA using oligo(dT)16as a primer. This was followed by PCR amplification of the first chain cDNA that encodes a part of PLCγ person (nucleotide 1593-2635, GenBank accession no. M34667)containing two SH2 domain and 2 tyrosine residue for phosphorylation using the oligonucleotides 5'-TATCCCCACTACTTTGTTCTGACCA-3' and 5'-CACGGGGTTGACCATCTCTTC-3'. PCR product clone to the vector pCR-Blunt II-TOPO using the kit to clone the Zero Blunt TOPO according to manufacturer's instructions. Cloned PLCγ check DNA sequencing and designated plasmid pCR-Blunt II-TOPO/PLCγ.

Design vector GST-PLCγ for expression in E.coli:

To construct a vector for expression of E. coli GST - PLCγ carry out PCR amplification PLCγ-part from pCR-Blunt II-TOPO/PLCγ, using the oligonucleotides: 5'-ACGGAATTCAGCACAGAGCTGCAGTCCAATG-3' (including siteEcoRIe) and 5'-GATGCGGCCGCTCTTTGACTGCACACTTGAAAGTTGG-3' (including siteNotI). Then this PCR product are ligated to the vector pGEX-4T-1, using sitesEcoRI andNotI for the expression of fused protein GST-PLCγ (see figure 1). Design test DNA sequencing and additional who have pMWM-79.

Obtaining GST-PLCγ:

Cells of Escherichia coli BL21 transformed plasmid pGEX-PLCγ DNA. Cultured bacteria to the value OD600approximately 0.5 in a shake incubator at 37°C and induce 1 mm isopropyl-β-D-thiogalactopyranoside (IPTG) for 4 hours. Bacteria precipitated by centrifugation at 4000 rpm for 20 min at 4°C and the residue freeze at -80°C over night. The next day the precipitate is re-suspended in NETN buffer (20 mm Tris-HCl pH 8.0, 10 mm NaCl, 1 mm EDTA, 500 μm Pefabloc, 10 μg/μl Leupeptin, 10 μg/ml Aprotinin, and 0.5% Triton X-100, 10 mm DTT) in a bath with ice. Bacteria are lysed in a bath with ice for 1 hour, adding 20 μg/ml lysozyme, before centrifugation at 10,000×g for 30 min at 4°C and transfer the supernatant to new tubes.

Purification of GST-PLCγ:

Beads glutathione-sepharose get by washing 3 times with 200 μl of beads HNT-buffer containing 30 mm HEPES pH 7.5, 30 mm NaCl and 0.1% Triton X-100, and then washing twice in NETN buffer. Then add to the glutathione beads-sepharose supernatant from lysed bacteria and the sample is left for 2 hours to rotate slowly at 4°C. Then fused protein GST-PLCγ adsorbed on glutathione beads-sepharose, washed three times in NETN buffer and clarify by centrifugation at 1000×g for 30 sec at 4°C, removing non-specific associated proteins. Next, the fused protein GST-PLCγ is separated from the beads by elution with 200 µl is the buffer for elution (50 mm Tris-HCl pH 8.0, 20 mm glutathione). The eluate explore the way SDS-PAGE with subsequent Coomassie-staining, as well as Western blotting, using antibodies anti-PLCγ (530) (sc-426) (1:1000) and anti-GST (B-14) (sc-138) (1:2000). The exit slit of the protein calculated from the absorbance at 280 nm.

Want to study compounds dissolved in DMSO at 10 mm and stored at -20°C and protect from light. The maximum concentration of DMSO inin vitrothe study is 0.1%. Control samples receive the same concentration of the solvent, as the samples treated with the test compounds. For studies of the kinase black 96-microtiter cell tablets MaxiSorp during incubation over night covered with 100 μl/cell solution of 2.5 mg/ml of phospholipase Cγ in TBS-buffer (40 mm Tris-HCl, pH of 7.4, 20 mm Mg(C2H3O2)2, of 0.02% NaN3) at 4°C. the Tablets are washed 3 times with TBS-buffer containing 0.1% Tween-20, and the remaining mask binding sites by incubation with 1% BSA in TBS buffer containing 0.1% Tween-20 for 1 hour. Tablets are again washed and add test compounds at final concentrations up to 10 μm together with ATP at a final concentration of 100 μm in 50 μl of TBS-buffer/cell. Then add 50 ál of human intracellular domain of KDR (VEGF receptor-2), diluted, ultimately, in the 3000-3500 times and incubated for 30 min at room temperature. Tablets are washed and in each cell is ice incubated with 100 μl labeled with europium anti-phosphotyrosine Anttila PY-20 (Wallac, FIN) at a concentration of about 114 ng/ml within 2 hours. Then the tablets are washed and in each cell incubated with 100 μl of enhancer solution (Wallac, FIN) for 5 min in the dark. Tablets read the meter for different labels Victor 1420, using europium Protocol for fluorometry resolution in time (Wallac, FIN): excitation 340 nm, emission 615 nm, the pulse cycle of a sample of 400 μs. Fluorescence determined for 400 μs between outbreaks after a delay of 400 μs. From all samples subtract the background measured in the absence of enzyme. Molar concentrations that inhibit 50% of the maximum enzyme activity (IC50), calculated from the curve dose-response, carrying out a straight line between the two concentrations, directly above and below the point of 50% inhibition (i.e. solving the equation y = a + bx).

In vitro KDR-inhibiting activity of the compounds of General formula (I) according to the present invention are listed in table 6.

Table 6
in vitro inhibition of KDR
Connection # -logIC50(KDR)
17,1
26,9
37,0
46,7
57,5
67,2
77,4
87,5
97,0
107,3
116,9
127,8
137,8
148,2
157,3
167,6
177,2
187,7
197,2
207,5
217,6
227,6
237,6
247,7
257,3
267,1
277,9
287,0
296,9
306,0
316,9
327,7
337,0
346,1
356,0
388,0
398,2
408,0
417,7
428,0
437,7
447,3
457,5
467,2
477,8
507,2
527,2
567,3
587,2
597,5
607,7
617,8
627,2
637,2
647,3
667,2
677,3
687,1
698,2
707,5
717,6
727,4
737,8
747,2
757,2
767,6
777,4
787,8
797,4
807,4
817,3
827,8
857,3
877,0
967,1
987,4
1007,2
1047,2
1067,3
1077,0
1107,1
1117,1
1138,6
1147,0
1167,4
1177,9
1187,8
1197,8
1207,4
1217,3
1228,1
1237,5
1247,2
1257,4
1268,1
1277,8
1287,8
1298,0
1307,3
1317,4
1327,0
1337,7
1347,6
1357,1
1417,3
1427,4
1437,0
156 7,2
1577,3
1587,1
1607,2
1617,2
1627,2
1648,1
1887,1
1957,1
1967,1
1987,2
1997,3
2047,2
2067,4
2077,1
2087,1
2108,1
2117,7
2128,0
2138,1
2147,3
2157,2
2168,0
2178,1
2197,4
2208,1
2218,1
2228,2
2237,5
2248,2
2258,1
2268,2
2278,3
2288,2
2298,1
2307,6
2317,4
2327,7
2338,0
2347,2
2357,2
2367,1
2377,1
2447,2
2458,1
2467,7
2477,3

Example 37:

Metabolic stability

Synthesis: comparative compounds 1 and 2 receive, using the methods described in WO 00/27819.

Method of selection: fresh rat (tac SPRD) hepatocytes secrete according to the method of the regional share. Cut off the right lateral lobe of the liver, put it on perfusion platform and first perfusion buffer without calcium, then a buffer containing calcium and collagenase. The cell suspension centrifuged and washed several times with cells.

Viability and out of cells: viability and output cells appreciate the way exclude the dye Trypan Blue. Use only cell suspensions with a viability above 80%. Prepare and use for research suspension of 2 x 106cells/ml

Study of the metabolic stability of test compounds (10 mm in DMSO) is placed in a liquid manipulator. The working solution A (200 μm) was prepared by transferring 10 ál of stock solution and 490 μl of 0.2% solution of bovine serum albumin(BSA) in buffer Krebs-Henseleit (KHB) on a microtiter plate. The working solution B (10 μm) to prepare, by transferring the microtiter plate 25 ál of the working solution A and 475 μl KHB with 0.2% BSA. Cells were diluted to 2 × 106cells/ml KHB with 0.2% BSA, then 475 μl of the suspension is transferred manually in each cell on two 24-cell plates (Costar, No. cat. 3524). The seeded cells are placed in a liquid optical drive and pre-incubated at 37°C for 20 min to activate the metabolic capacity of cells. After pre-incubation, add to each cell of 25 µl of the working solution B (10 μm), receiving a final concentration of 0.5 μm of the test compounds in cell suspension. After adding all the cells on the tablet test connection the tablet gently mixed and incubated. After 15, 30, 60, 90 and 120 min select a sample of 25 μl and added to microtiter plate containing 100 μl of methanol with internal standard to stop the metabolic reactions. Microtiter plate centrifuged (30 min, 4500 rpm) and analyze the supernatant by LC-MS/MS (see research). Samples of t=0 receive manually adding 190 μl of cell suspension to each cell of the 96-cell tablet (Costar, No. cat. 3594; the same material and at the 24-cell tablets). Add to each cell 10 ál of the working solution B. After each of the four compounds (4 needles for liquid manipulation is the er) tablet shaken and immediately selected a sample of 25 μl and transferred to a microtiter plate, containing 100 μl of methanol with internal standard. Samples analyzed as described below.

Study: HPLC system consists of a pump Agilent 1100, column heater and autosampler CTC HTS-PAL. Mass spectrometer (Sciex API 3000 MS/MS. Conditions chromatography was carried out as follows: column Bond Sb-C18, 5 μm, and 2.1 × 50 mm; injected volume : 10 μl; eluent A: 5% methanol in MilliQ-water (vol./about. %), 2 mm ammonium acetate, 20 mm formic acid; eluent B: 90% methanol in MilliQ-water (vol./about. %), 2 mm ammonium acetate, 20 mm formic acid; flow rate of 500 μl/min; the program stepwise gradient: 0-2 min 0% B -> 100% B; 2-3 min 100% B; 3-3,1 min 100% B → 0% B; 3,1-5 min 0% B.

Data is processed using Analyst version 1.2. Conditions for all connections fit and optimize the mass spectrometer as you type.

Calculations: the initial concentration of the test compound is defined as 100% and note on the chart the number of unchanged compounds (%) versus time. The area under the curve (AUC) calculated using the linear trapezoid method:

Linear trapezoidal rule:

AUC values for each connection normalized, resulting in values between 0 and 100, and this number is used as a measure of metabolic stability. Connection with AUC values close to 0, have a low metabolic stability, whereas compounds with values of AUC, liscie to 100, have a high metabolic stability.

Table 6
Metabolic stability derivatives of Anthranilic acid amide of the General structure A and esters, hydroxamic acids of General formula I
ConnectionAUC (normer.)

Comparative compound 1: Anthranilic acid amide according to WO 00/27819
10

Comparative compound 21: Anthranilic acid amide according to WO 00/27819
12

Connection 1
16

The connection 29
65

1. The compound of General formula I
[I]
where R1denotes hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical;
D represents a nitrogen atom or C-R2;
E represents a nitrogen atom or C-R3;
F denotes a nitrogen atom or C-R4;
G represents a nitrogen atom or C-R5;
R2, R3, R4and R5are odinakovymi different and individually represent hydrogen, halogen, alkoxy or linear or branched, saturated or unsaturated hydrocarbon radical;
W represents an oxygen atom;
X denotes a radical of the formula -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, in which k, m, r and s are equal integers from 0 to 6, and n is an integer from 1 to 6, and these radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;
Y denotes a radical of the formula -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-in which i, j, n, r, s, t and u are equal to integers from 0 to 6, and these radicals are optionally substituted C1-3the alkyl, HE or1-3alkyl-C1-3alkylsulfonamides;
R7denotes hydrogen, oxo, thioxo, halogen, hydroxyl, amino, carboxy, carbarnoyl, cyano, cycloalkyl, alkyl, aryl, heteroaryl, heteroseksualci, heterocyclisation, alkoxy, alkoxyamino, alkoxycarbonyl, alkylcarboxylic, alkenylboronic, alkylsulphonyl, aminosulfonyl, arylsulfonyl, aminocarbonyl, alkylcarboxylic, and these amino, cycloalkyl, alkyl, aryl, heteroaryl, heteroseksualci, heteroseksualci-heteroaryl, Alcock and, alkoxyimino, alkoxycarbonyl, alkylcarboxylic, alkenylboronic, alkylsulphonyl, aminosulfonyl, arylsulfonyl, aminocarbonyl, alkylcarboxylic optionally are substituted by one or more substituents independently selected from the group comprising hydrogen, halogen, oxo, hydroxyl, cyano, alkoxy, alkoxycarbonyl, alkylsulfonyl, aryl, heteroaryl, alkyl and alkenyl;
In denotes aryl, heteroaryl, heteroseksualci, geteroseksualen, cycloalkyl or cycloalkenyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8;
R8denotes hydrogen, halogen, hydroxyl, amino, imino, oxo, thioxo, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkylsulfonyl, aminocarbonyl, allylurea, allylthiourea, aminocarboxylate, alkylcarboxylic, geterotsiklicheskikh, heteroseksualci, geteroseksualen, aryl, heteroaryl, alkylaminocarbonyl and linear or branched, saturated or unsaturated hydrocarbon radical, and these amino, alkoxy, alkylthio, alkoxycarbonyl, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, alkylsulphonyl, alkylsulfonyl, amino shall arbonyl, alkaluria, allylthiourea, aminocarboxylate, alkylcarboxylic, geterotsiklicheskikh, heteroseksualci, geteroseksualen, aryl, heteroaryl, alkylaminocarbonyl and linear or branched, saturated or unsaturated hydrocarbon radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;
And denotes a linear, branched and/or cyclic, saturated or unsaturated hydrocarbon radical, heteroseksualci, geteroseksualen or heteroaryl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9;
R9denotes hydrogen, oxo, halogen, trifluoromethyl, hydroxyl, amino, nitro, carboxy, cyano, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, alkoxycarbonyl, allylurea, allylthiourea, alkylsulphonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylboronic, alkylsulfonyl, formyl, aminocarbonyl, alkylcarboxylic, aminocarboxylate, heteroseksualci, heteroaryl and linear or branched, saturated or unsaturated hydrocarbon radical, and these amino, alkoxy, alkylthio, alkoxycarbonyl, alkylcarboxylic, arcoxia is bonelace, alkaluria, allylthiourea, alkylsulphonyl, aminosulfonyl, arylsulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylboronic, alkylsulfonyl, aminocarbonyl, alkylcarboxylic, aminocarboxylate, heteroseksualci, heteroaryl and linear or branched, saturated or unsaturated hydrocarbon radicals optionally are substituted by one or more substituents independently selected from the group consisting of R7;
and its pharmaceutically acceptable salt, hydrate or solvate;
provided that the connection is not
6-methoxy-N-(2-ethoxycarbonylphenyl)PP,
6-methoxy-N-[2-(methoxymethylethoxy)phenyl] - PP,
(2-chloro-6-isopropoxycarbonyl)amidon 2-(2-chlorophenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid,
(2-chloro-6-isopropoxycarbonyl)amidon 2-(3-chloropyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid,
(2-isopropoxycarbonyl-6-were)amidon 2-(3-chloropyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid,
(2-isopropoxycarbonyl-6-were)amidon 2-(3-chlorophenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid,
2-(2-chloro-2-phenylacetylamino)-N-methoxybenzamide,
3-chloro-2-(2-chloro-2-phenylacetylamino)-N-methoxybenzamide,
3,5-dichloro-2-(2-chloro-2-phenylacetylamino)-N-methoxybenzamide,
2-(3-{4-[2-(2,2,2-triptonite the si)phenyl]piperazine-1-yl}propylamino)-N-methyl-N-methoxynicotinate.

2. The compound according to claim 1, in which R1denotes hydrogen.

3. The compound according to claim 1 or 2, in which D represents C-R2E represents C-R3F denotes the C-R4and G represents C-R5.

4. The compound according to claim 1 or 2, in which R2, R3, R4and R5represent hydrogen, chlorine, bromine, fluorine, methoxy or methyl.

5. The compound according to claim 1 or 2, in which D represents a nitrogen atom, E represents C-R3F denotes the C-R4and G represents C-R5.

6. The compound according to claim 1 or 2, in which R3, R4and R5denote hydrogen.

7. The compound according to claim 1 or 2, in which D represents C-R2E denotes the nitrogen atom, F represents C-R4and G represents C-R5.

8. The compound according to claim 1 or 2, in which R2, R4and R5denote hydrogen.

9. The compound according to claim 1 or 2, where In denotes phenyl or pyridyl, for example 2-pyridyl, 3-pyridyl or 4-pyridyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8.

10. The compound according to claim 1 or 2, where In denotes naphthyl, 2,3-dihydrobenzofuranyl, benzofuranyl 2N-chromanol, thiazolyl, 4,5-dihydro-1H-[1,2,4]-triazolyl, tetrahydropyranyl, 1,6-dihydropyridine, imidazolyl, imidazolidinyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolyl, Piperi inil, pyrrolidinyl, 4,5-dihydrooxazolo, isoxazolyl, 4,5-dihydroisoxazole, pyrimidinyl, 1-N-pyrazolyl, 1H-indazol-6-yl, chinolones or ethanolamines, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R8.

11. The compound according to claim 1 or 2, in which R8denotes hydrogen, halogen, alkoxy, alkoxycarbonyl, carboxy, aminocarbonyl, alkoxycarbonyl, cyano, alkyl, oxo, hydroxy, amino, heteroseksualci, geteroseksualen, alkylsulfonyl, allylurea, allylthiourea, alkylcarboxylic, geterotsiklicheskikh or aminocarboxylate where specified alkoxy, alkoxycarbonyl, alkoxycarbonyl, aminocarbonyl, alkyl, amino, heteroseksualci, alkylsulfonyl, allylurea, allylthiourea, alkylcarboxylic, geterotsiklicheskikh or aminocarbonyl optionally are substituted by one or more substituents independently selected from the group consisting of R7.

12. The compound according to claim 1 or 2, in which R8denotes hydrogen, fluorine, chlorine, bromine, cyano, carboxy, oxo, -NH2, hydroxy, methoxy, methoxycarbonyl, etoxycarbonyl, methoxycarbonyl, tert-butoxycarbonyl, methylaminomethyl, pyrrolidinylcarbonyl, ethylaminomethyl, propylaminoethyl, butylamino arbonyl, methyl, ethyl, propyl, morpholine, pyrrolidine, methylsulfonylamino, macilwraith, amiloride, tert-butylurea, cyclohexylurea, methylthiourea, isopropylamino, n-propylurea, methylamino or ethylamino, where mentioned methoxy, methoxycarbonyl, etoxycarbonyl, methoxycarbonyl, tert-butoxycarbonyl, methylaminomethyl, pyrrolidinylcarbonyl, ethylaminomethyl, propylaminoethyl, butylaminoethyl, methyl, ethyl, propyl, morpholine, pyrrolidine, methylsulfonylamino, macilwraith, amiloride, tert-butylurea, cyclohexylurea, methylthiourea, isopropylamino, n-propylurea, methylamino or ethylamino optionally are substituted by one or more substituents independently selected from the group consisting of R7.

13. The compound according to claim 1 or 2, in which X represents-CH2-, -(CH2)2-, -CH(CH3)-, -C(O)-, -C(O)-CH2- or -(CH2)2-O-CH2-.

14. The compound according to claim 1 or 2, in which Y denotes a radical of the formula -(CH2)iNH-C(O)-(CH2)j-where i is an integer from 1 to 4 and j is 0; or Y denotes a radical of the formula -(CH2)n-, where n is an integer from 0 to 6; or Y denotes a radical of the formula -(CH2)r-O-(CH2)swhere r is an integer from 0 to 6 and s is an integer from 0 to 1; or Y denotes a radical of the formula -(CH )t-NH-(CH2)u-where t is an integer from 0 to 4; u is an integer from 0 to 1; where these radicals optionally substituted C1-3the alkyl, HE or1-3alkyl-C1-3alkylsulfonamides.

15. The compound according to claim 1 or 2, in which Y denotes a link-CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-O-, -(CH2)2-O-CH2-, -(CH2)3-O-CH2-, -(CH2)3-NH-C(O)-, -(CH2)4-NH-C(O)-, -CH2-CH(OH)-CH2-O-, -(CH2)2-NH-CH2-, -(CH2)4-NH-CH2-, -CH2-CH2-CH2- or-CH(CH2NHSO2CH3)-.

16. The compound according to claim 1 or 2, in which And indicates (With6-C10)aryl, (C3-C10)heteroseksualci, (C3-C10)cycloalkyl, (C3-C6)cycloalkenyl, (C2-C5)alkenyl, (C1-C6)alkyl, (C2-C10)heteroaryl, geteroseksualen or toluyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9.

17. The compound according to claim 1 or 2, where And denotes methyl, ethyl, (C6)aryl, (C9)aryl, (C10)aryl, (C3)alkyl, (C4)alkyl, (C5)alkyl, (C2)alkenyl, (C3)alkenyl, (C4)alkenyl, (C5)alkenyl, (C3)cycloalkyl, ( 4)cycloalkyl, (C5)cycloalkyl, (C6)cycloalkyl, (C7)cycloalkyl, (C8)cycloalkyl, (C10)cycloalkyl, (C6)cycloalkenyl, (C3)heteroaryl, (C4)heteroaryl, (C5)heteroaryl, (C6)heteroaryl, (C7)heteroaryl, (C9)heteroaryl, (C4)heteroseksualci, (C5)heteroseksualci, (C3)geteroseksualen, (C4)geteroseksualen, (C5)geteroseksualen or toluyl, all of which optionally are substituted by one or more substituents independently selected from the group consisting of R9.

18. The compound according to claim 1 or 2, where And denotes methyl, ethyl, allyl, butenyl, phenyl, thiazolyl, pyridyl, tert-butyl, propyl, pentyl, isobutyl, benzo[1,3]dioxole, indanyl, naphthyl, thiazolyl, thiophenyl, oxadiazolyl, isoxazolyl, cyclopropyl, cyclobutyl, [1,2,3]triazolyl, cyclopentyl, cyclohexyl, cyclohexenyl, substituted, bicyclo[2.2.1]heptenyl, bicyclo[2.2.1]heptyl, bicyclo[4,1,0]heptenyl, cycloheptyl, cyclooctyl, chinolones, tetrahydropyranyl, 4,5-dihydrooxazolo or tetrahydropyranyl that all are optional substituted by one or more substituents independently selected from the group consisting of R9.

19. The compound according to claim 1 or 2, in which R9denotes hydrogen, nitro, halogen, oxo, cyano, triptime is l, carboxy, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkenyl, quinil, alkylthio, heteroseksualci, heteroaryl, amino, arylsulfonyl, allylthiourea, allylurea, heteroarylboronic, alkylsulfonyl, aminocarbonyl, aminocarbonyl, aryl, where these alkoxycarbonyl, alkyl, cycloalkyl, alkenyl, quinil, alkylthio, heteroseksualci, heteroaryl, amino, arylsulfonyl, allylthiourea, allylurea, heteroarylboronic, alkylsulfonyl, aminocarbonyl, aminocarbonyl or aryl optionally are substituted by one or more substituents independently selected from the group consisting of R7.

20. The compound according to claim 1 or 2, in which R9denotes hydrogen, nitro, fluorine, chlorine, bromine, iodine, oxo, cyano, carboxy, ethynyl, ethinyl, PROPYNYL, butynyl, methoxy, aminomethyl, aminoethyl, AMINOPHENYL, morpholine, carbomethoxy, cyano, trifluoromethyl, methyl, tert-butoxy, ethyl, propyl, butyl, pentyl, cyclopentyl, nonanal, methylsulfanyl, aminocarbonyl-tert-butoxy, methylsulfonylamino, thiazolecarboxamide, phenylcarbonylamino, -NH-C(S)-NH2, -NH-(CO)-NH2morpholinyl, ethylaminomethyl, thiophene, amino or phenyl, where mentioned ethynyl, ethinyl, PROPYNYL, butynyl, methoxy, ethoxy, aminomethyl, aminoethyl, morpholine, carbomethoxy, cyano, trifluoromethyl, methyl, ethyl, propyl, butyl, p is until, cyclopentyl, nonanal, methylsulfanyl, methylsulfonylamino, thiazolecarboxamide, phenylcarbonylamino, -NH-C(S)-NH2, -NH-C(O)-NH2morpholinyl, ethylaminomethyl, thiophene, amino or phenyl, optionally are substituted by one or more substituents independently selected from the group consisting of R7.

21. The compound according to claim 1 or 2, in which R7denotes hydrogen, halogen, hydroxy, carboxy, carbarnoyl, cyano, oxo, thioxo, aryl, alkyl, alkoxy, arylsulfonyl, aminocarbonyl, heterocyclisation, heteroseksualci, heteroaryl, alkoxycarbonyl, alkoxy, alkoxyamino, alkylcarboxylic, alkenylboronic, cycloalkyl or amino, where these aryl, alkyl, alkoxy, alkoxyamino, arylsulfonyl, aminocarbonyl, heterocyclisation, heteroseksualci, heteroaryl, alkoxycarbonyl, alkoxy, alkylcarboxylic, alkenylboronic, cycloalkyl or amino optionally are substituted by one or more substituents independently selected from the group comprising halogen, hydroxy, cyano, amino, alkyl, alkoxy, aryl or oxo.

22. The compound according to claim 1 or 2, in which R7denotes hydrogen, hydroxy, amino, -NH2diethylamino, cyclohexylamino, tert-butylamino, oxo, thioxo, phenyl, pyridyl, acetylamino, chlorine, methyl, ethyl, propyl, butyl, morpholine, methoxy, tert-is ataxi, cyclopropyl, hydroxyethyl, methoxyimino, -NH-phenyl, TRIFLUOROACETYL, acetyl, ethoxy, 2-acetylamino-4-methylthiazole, tert-butyl, methylpiperazine, 2-hydroxyethylpiperazine, methylthiazole, hydroxypyrrolidine, dimethylamino, toluyl, trifluoromethyl, methylamino, pyrrolidin, methoxycarbonyl, etoxycarbonyl, carboxy, carbarnoyl, cyano, methylcarbonate, ethylcarbonate, acryloyloxy, cyclopropyl or 2.5-dioxoimidazolidin.

23. The compound according to claim 1 or 2, which represents 4-pyridyl, optionally substituted in position 2 by a substituent R8or denotes phenyl, optionally substituted with substituents R8(up to two), the same or different.

24. The compound according to claim 1 or 2, selected from the group including
N-benzyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 1),
N-(4-nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 2),
N-(2-nitrobenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 3),
2-[(pyridine-4-ylmethyl)amino]-N-(3-triftormetilfosfinov)benzamide (compound 4),
2-[(pyridine-4-ylmethyl)amino]-N-(2-triftormetilfosfinov)benzamide (compound 5),
N2-[(pyridine-4-ylmethyl)amino]-N-(4-triftormetilfosfinov)benzamide (compound 6),
N-(4-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 7),
N-(3-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 8),
2-[(Piri is in 4-ylmethyl)amino]-N-(3,4,5-trimethoxybenzoate)benzamide (compound 9),
N-(4-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 10),
N-(3-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 11),
N-(2-chlorobenzoyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 12),
N-(2-bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 13),
N-(2,4-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 14),
N-(3,4-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 15),
N-(2,6-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 16),
N-(3,5-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 17),
N-(2,3-DICHLOROSILANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 18),
N-(2,5-dichloraniline)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 19),
N-(2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 20),
N-(3-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 21),
N-(4-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 22),
N-(2-chloro-6-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 23),
N-(2-chloro-4-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 24),
N-(3-chloro-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 25),
methyl Efir-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 26),
N-(4-cyanobenzyl)-2-[(feast of the DIN-4-ylmethyl)amino]benzamide (compound 27),
2-[(pyridine-4-ylmethyl)amino]-N-(quinoline-2-ylethoxy)benzamide (compound 28),
N-phenoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 29),
N-(2-phenoxyethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 30),
N-(3-phenylpropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 31),
N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 32),
N-benzyloxy-2-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 33),
2-(4-forbindelsen)-N-(4-methoxybenzyloxy)nicotinamide (compound 34),
2-(4-methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 35),
N-(4-cianfrocca)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 36),
N-(4-bromophenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 37),
N-(4-fluoro-2,6-dimethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 38),
N-(4-fluoro-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 39),
N-(2,3-debtor-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 40),
N-(3-fluoro-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 41),
N-(5-fluoro-2-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 42),
2-[(pyridine-4-ylmethyl)amino]-N-(2,3,5,6-titrator-4-methoxybenzyloxy)benzamide (compound 43),
N-(4-bromobenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 44),
N-(2-jobensitas)-2-[(pyridine-4-ileti is)amino]benzamide (compound 45),
N-(3-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 46),
N-(4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 47),
N-[2-(3,3-dimethylbutan-1-enyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 48),
2-[(pyridine-4-ylmethyl)amino]-N-(2-streventname)benzamide (compound 49),
N-[3-(3-hydroxyprop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 50),
N-[3-(5-CANopen-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 51),
N-[2-(3-hydroxyprop-1-inyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 52),
2-[3-(2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl} phenyl)prop-2-ynyloxy]ethyl ester acetic acid (compound 53),
N-[2-(3-methyl-3H-imidazol-4-ylethynyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 54),
N-[3-(3-methyl-3H-imidazol-4-ylethynyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 55),
N-(2-cyanomethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 56),
N-(2-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 57),
N-(4-hydroxymethylbenzene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 58),
N-(4-fluoro-2-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 59),
N-(2-fluoro-6-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 60),
N-(4-ft is R-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 61),
N-(4-methyl-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 62),
N-(4-methoxy-3-triftormetilfosfinov)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 63),
N-(2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 64),
N-(4-interoceanica)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 65),
2-[(pyridine-4-ylmethyl)amino]-N-(2-cryptomaterial)benzamide (compound 66),
2-[(pyridine-4-ylmethyl)amino]-N-(3-cryptomaterial)benzamide (compound 67),
2-[(pyridine-4-ylmethyl)amino]-N-(4-cryptomaterial)benzamide (compound 68),
N-(2-differentoccasions)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 69),
2-[(pyridine-4-ylmethyl)amino]-N-(2-triftormetilfullerenov)benzamide (compound 70),
N-(6-chlorobenzo[1,3]dioxol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 71),
N-(benzo[1,3]dioxol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 72),
N-(indan-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 73),
N-(3-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 74),
N-(2-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 75),
N-(4-cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 76),
N-(3-bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 77),
N-(2-chloro-4-zenobe is siloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 78),
N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 79),
N-(4-cyano-2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 80),
N-(2-bromo-5-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 81),
N-(4-cyanonaphthalene-1 ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 82),
N-(4-(morpholine-4-ivasilaki)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 83),
N-(2-morpholine-4-yl-benzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 84),
N-(2-aminobenzoate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 85),
N-(2-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 86),
methyl ester of 3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 87),
3-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 88),
4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}benzoic acid (compound 89),
N-[4-(morpholine-4-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 90),
N-{3-[4-(3-cyano-2-yl)piperazine-1-carbonyl]benzyloxy}-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 91),
N-[3-(4-methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 92),
N-[3-(morpholine-4-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 93),
N-[3-(3-hydroxyp Raiden-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 94),
N-[4-(4-methylpiperazin-1-carbonyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 95),
N-[3-(2-dimethylaminoethanol)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 96),
N-[3-(2-pyrrolidin-l-iletileri)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 97),
2-[(pyridine-4-ylmethyl)amino]-N-(2-thiophene-2-ivasilaki)benzamide (compound 98),
N-(4'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 99),
N-(naphthalene-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 100),
N-(1-phenylethane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 101),
2-[(pyridine-4-ylmethyl)amino]-N-[1-(2-triptoreline)ethoxy]benzamide (compound 102),
N-(pyridine-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 103),
N-(2,6-dichloropyridine-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 104),
2-[(pyridine-4-ylmethyl)amino]-N-(thiazole-4-ylethoxy)benzamide (compound 105),
N-(2-chlorothiazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 106),
N-(2-phenylthiazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 107),
N-(5-methylisoxazol-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 108),
N-(3,5-dimethylisoxazol-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 109),
N-(3-propylenoxide-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (with the unity 110),
N-(5-chlorothiophene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 111),
N-[2-(4-cyanophenyl)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 112),
N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 113),
N-cyclopropylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 114),
N-methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 115),
N-(2,2-DIMETHYLPROPANE)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 116),
N-(2-ethylbutane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 117),
N-(3-methylbutoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 118),
N-cyclobutylmethyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 119),
N-cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 120),
N-cyclohexylmethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 121),
N-cyclooctylmethyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 122),
N-(1-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 123),
N-cyclohexyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 124),
N-(2-cyclopropylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 125),
N-(2-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 126),
N-(3-cyclopentyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 127),
N-(cyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide connection 128),
N-(6-methylcyclohex-3-animetake)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 129),
N-(TRANS-4-hydroxymethylglycinate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 130),
N-(3-methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 131),
N-(adamantane-1-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 132)
N-(bicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 133),
N-(6,6-dimethylbicyclo[3.1.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 134),
2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-2-ylethoxy)benzamide (compound 135),
2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydrofuran-3-ylethoxy)benzamide (compound 136),
N-(3-methyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 137),
N-(3-ethyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 138),
N-(3-butyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 139),
2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-yloxy)benzamide (compound 140),
2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-4-ylethoxy)benzamide (compound 141),
2-[(pyridine-4-ylmethyl)amino]-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 142),
4-fluoro-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 143),
2-fluoro-N-(2-m is triazol-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 144),
5-fluoro-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 145),
3-methoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 146),
N-(4-chlorobenzoyloxy)-3-methoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 147),
4,5-dimethoxy-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 148),
N-benzyloxy-4,5-dimethoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 149),
2-methyl-N-(2-methylthiazole-4-ylethoxy)-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 150),
N-benzyloxy-2-methyl-6-[(pyridine-4-ylmethyl)amino]benzamide (compound 151),
5-methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 152),
N-benzyloxy-5-methyl-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 153),
5-bromo-N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 154),
N-benzyloxy-5-bromo-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 155),
N-(4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 156),
N-(2-chloro-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 157),
N-(4-cyano-2-forbindelse)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 158),
N-(3-bromo-4-cyanobenzyl)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 159),
N-(2-jobensitas)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 160),
N-(2-b is obesiance)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 161),
N-(4-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 162),
N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 163),
N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 164),
N-benzyloxy-2-(4-forbindelsen)nicotinamide (compound 165),
N-benzyloxy-2-(4-chlorobenzylamino)nicotinamide (compound 166),
N-benzyloxy-2-(4-methoxybenzylamine)nicotinamide (compound No. 167),
N-(4-cyano-2-methoxybenzyloxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 169),
N-benzyloxy-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 170),
N-(2-methylthiazole-4-ylethoxy)-3-[(pyridine-4-ylmethyl)amino]isonicotinamide (compound 171),
N-benzyloxy-2-(4-forbindelsen)benzamide (compound 172),
N-(4-cyanobenzyl)-2-(4-forbindelsen)benzamide (compound 173),
2-(4-forbindelsen)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 174),
N-benzyloxy-2-(3-cyano-4-forbindelsen)benzamide (compound 175),
N-(2-bromobenzylamine)-2-(3-cyano-4-forbindelsen)benzamide (compound 176),
methyl ester 5-[(2-benzyloxycarbonylamino)methyl]-2-fermenting acid (compound 177),
methyl ester 5-[(2-cyclopentanecarbonitrile)methyl]-2-fermenting acid (compound 178),
methyl ester 2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl}benzo is Noah acid (compound 179),
methyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-2-fermenting acid (compound 180),
5-[(2-cyclopentanecarbonitrile)methyl]-2-Formentera acid (compound 181),
2-fluoro-5-{[2-(4-forantimicrobial)phenylamino]methyl} benzoic acid (compound 182),
5-[(2-benzyloxycarbonylamino)methyl]-2-Formentera acid (compound 183),
5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(2-hydroxyethyl)benzamide (compound 184),
5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 185),
5-[(2-benzyloxycarbonylamino)methyl]-2-fluoro-N-(4-hydroxybutyl)benzamide (compound 186),
5-[(2-benzyloxycarbonylamino)methyl]-N-(3-dimethylaminopropyl)-2-perbenzoic (compound 187),
5-[(2-cyclopentanecarbonitrile)methyl]-2-fluoro-N-(3-hydroxypropyl)benzamide (compound 188),
N-cyclopentyloxy-2-[4-fluoro-3-(4-methylpiperazin-1-carbonyl)benzoylamino]benzamide (compound 189),
N-cyclopentyloxy-2-[4-fluoro-3-(morpholine-4-carbonyl)benzoylamino]benzamide (compound 190),
N-benzyloxy-2-(4-methoxybenzylamine)benzamide (compound 191),
2-(4-methoxybenzylamine)-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 192),
N-benzyloxy-2-[(4-methoxynaphthalene-1-ylmethyl)amino]benzamide (compound 193),
N-(4-cyanobenzyl)-2-[(4-methoxynaphthalene-1-ylmethyl)am is but]benzamide (compound 194),
2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 195),
N-(4-cyanobenzyl)-2-[(2,3-dihydrobenzofuran-5-ylmethyl)amino]benzamide (compound 196),
2-[(benzofuran-5-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 197),
2-[(benzofuran-5-ylmethyl)amino]-N-benzyloxybenzoate (compound 198),
2-[(benzofuran-5-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 199),
N-(4-cyanobenzyl)-2-[(2-oxo-2H-chromen-6-ylmethyl)amino]benzamide (compound 200),
N-(4-chlorobenzoyloxy)-2-(4-cyanobenzylidene)benzamide (compound 201),
2-[(3,5-dichloropyridine-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 202),
N-benzyloxy-2-[(3,5-dichloropyridine-4-ylmethyl)amino]benzamide (compound 203),
2-[(2-bromopyridin-4-ylmethyl)amino]-N-(4-forbindelse)benzamide (compound 204),
N-(4-cyano-2-methoxybenzyloxy)-2-[(2-hydroxypyridine-4-ylmethyl)amino]benzamide (compound 205),
2-[(2-aminopyridine-4-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 206),
N-(4-forbindelse)-2-[(2-morpholine-4-yl-pyridine-4-ylmethyl)amino]benzamide (compound 207),
N-cyclopentyloxy-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (compound 208),
N-(4-cyanobenzyl)-2-[(2-methanesulfonylaminoethyl-4-ylmethyl)amino]benzamide (compound 209),
N-(4-cyanobenzyl)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (link is 210),
N-(4-cyano-2-methoxybenzyloxy)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 211),
N-cyclopentyloxy-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 212),
N-(2,3-debtor-4-methylbenzylamino)-2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}benzamide (compound 213),
ethyl ester of[3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 214),
ethyl ester of (3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (compound 215),
[3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl}pyridine-2-yl)ureido]acetic acid (compound 216),
(3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)acetic acid (compound 217),
2-[3-(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)ureido]ethyl ester 2-methylacrylate acid (compound 218),
2-(3-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}ureido)ethyl ester 2-methylacrylate acid (compound 219),
N-(4-cyanobenzyl)-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}-amino)benzamide (compound 220),
N-cyclopentyloxy-2-({2-[3-(2-hydroxyethyl)ureido]pyridine-4-ylmethyl}amino)benzamide (compound 221),
(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-ylcarbonyl)methyl ester acetic acid (connected to the e 222),
{4-[(2-cyclopentanecarbonyl phenylamino)methyl]pyridine-2-ylcarbonyl}methyl ether acetic acid (compound 223),
N-(4-cyanobenzyl)-2-{[2-(2-hydroxyacetylamino)pyridine-4-ylmethyl]amino}benzamide (compound 224),
ethyl ester of 4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)carbamino acid (compound 225),
N-(4-cyanobenzyl)-2-{[2-(cyclopropanecarbonyl)pyridine-4-ylmethyl]amino}benzamide (compound 226),
N-cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)pyridine-4-ylmethyl]amino}benzamide (compound 227),
N-cyclopentyloxy-2-({2-[2-(2,5-dioxoimidazolidin-4-yl)acetylamino]pyridine-4-ylmethyl}amino)benzamide (compound 228),
2-[(2-aminopyridine-4-ylmethyl)amino]-N-Cyclopentasiloxane (compound 229),
N-benzyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 230),
N-(4-cyanobenzyl)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 231),
N-(2-methylthiazole-4-ylethoxy)-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 232),
N-cyclopentyloxy-2-[(quinoline-4-ylmethyl)amino]benzamide (compound 233),
2-[(quinoline-4-ylmethyl)amino]-N-(tetrahydropyran-4-ylethoxy)benzamide (compound 234),
N-(4-cyano-2-methoxybenzyloxy)-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 235),
N-benzyloxy-2-[(6-methoxypyridine-3-ylmethyl)amino]benzamide (compound 236),
N-(4-cyanobenzyl)-2-[(6-methox the pyridine-3-ylmethyl)amino]benzamide (compound 237),
N-benzyloxy-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 238),
N-(2,4-dichloraniline)-2-[(thiazol-5-ylmethyl)amino]benzamide (compound 239),
N-(2-methylthiazole-4-ylethoxy)-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 240),
N-benzyloxy-2-[(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylmethyl)amino]benzamide (compound 241),
N-benzyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 242),
N-cyclopentyloxy-2-(2-imidazol-1-ylethylamine)benzamide (compound 243),
N-(4-cyanobenzyl)-2-(1-pyridine-4-ylethylamine)benzamide (compound 244),
2-{[2-(3-methylurea)pyridine-4-ylmethyl]amino}-N-(tetrahydropyran-2-ylethoxy)benzamide (compound 245),
N-cyclopentyloxy-2-{[2-(2-methoxyethylamine)pyridine-4-ylmethyl]amino}benzamide (compound 246),
N-(4-cyanobenzyl)-2-[(6-oxo-1,6-dihydropyridines-3-ylmethyl)amino]benzamide (compound 247),
N-cyclopentyloxy-2-[(tetrahydropyran-4-ylmethyl)amino]benzamide (compound 248),
N-(3-iodine-4-methylbenzylamino)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 250),
N-(4-ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 251),
N-(4-isopropylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 252),
N-(4-tert-butylbenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 253),
N-(2-ethylbenzylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 254),
N-(2-universilence)-2-[(n is ridin-4-ylmethyl)amino]benzamide (compound 255),
N-(4-phenylenedimethylene)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 256),
N-(4-diethylaminoethylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 257),
N-(2-carbamoylphenoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 258),
N-[4-cyano-2-(2-methoxyethoxy)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 259),
N-(4-cyanomethyl-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 260),
N-(5-cyano-2-methoxybenzyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 261),
tert-butyl ester 2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}phenyl)carbamino acid (compound 262),
N-(2-acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 263),
N-(2-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 264),
N-(2-methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 265),
N-(4-acetylaminobenzoic)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 266),
N-(biphenyl-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 267),
N-(biphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 268),
N-(3'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 269),
N-(2'-methoxybiphenyl-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 270),
N-(3'-hydroxymethyluracil-2-elmet the XI)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 271),
N-(3-phenoxybenzyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 272),
N-(anthracene-9-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 273),
N-[4-(2-methylthiazole-4-yl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 274),
N-(2-methanesulfonamido-1 venlafaxi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 275),
2-[(pyridine-4-ylmethyl)amino]-N-[2-(4-triptoreline)thiazole-4-ylethoxy]benzamide (compound 276),
2-[(pyridine-4-ylmethyl)amino]-N-(3-para-tolerization-5-ylethoxy)benzamide (compound 277),
N-(3-methylisoxazol-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 278),
N-(3-utilization-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 279),
N-(3-butylisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 280),
N-(3-penilesecrets-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 281),
2-[(pyridine-4-ylmethyl)amino]-N-[5-(3-triptoreline)-[1,2,4]oxadiazol-3-ylethoxy]benzamide (compound 282),
N-(1-benzyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 283),
N-(1-cyclopentyl-1H-[1,2,3]triazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 284),
N-(5-oxo-4,5-dihydro-1H-[1,2,4]triazole-3-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 285),
N-(3-phenoxypropane)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 286),
N-(3-BAA is selectedtopics)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 287),
N-(2-benzyloxyethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 288),
N-[2-hydroxy-3-(4-methoxyphenoxy)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 289),
N-(3-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 290),
N-(4-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 291),
N-(2-methanesulfonylaminoethyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 292),
N-(4-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 293),
N-(3-benzensulfonamidelor)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 294),
N-[2-(4-cyanobenzenesulfonyl)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 295),
N-[3-(4-cyanobenzenesulfonyl)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 296),
N-(3-phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 297),
N-(2-phenylmethanesulfonyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 298),
N-[3-(2-acetylamino-4-methylthiazole-5-sulfonylamino)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 299),
N-[2-(2-acetylamino-4-methylthiazole-5-sulfonylamino)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 300),
N-(2-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 301),
N-(4-benzylaminopurine)-2-[(pyridine-4-ylmethyl)amino]benzamide (Conn is out 302),
tert-butyl ether (2-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}ethyl) - carbamino acid (compound 303),
tert-butyl methyl ether (3-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}propyl)carbamino acid (compound 304),
tert-butyl ester (4-{2-[(pyridine-4-ylmethyl)amino]benzoylamino}butyl)carbamino acid (compound 305),
N-[2-(3-phenylthioureido)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 306),
N-[4-(3-phenylthioureido)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 307),
N-[2-(3-phenylurea)ethoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 308),
N-[3-(3-phenylurea)propoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 309),
N-[4-(3-phenylurea)butoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 310),
N-(2-aminoethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 311),
N-(3-aminopropoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 312),
N-(4-aminobutoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 313),
N-(2-morpholine-4-yl-2-oksidoksi)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 314),
N-[(2-methoxyphenylacetyl)methoxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 315),
N-tert-butoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 316),
N-isobutoxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 317),
N-(2-methylacrylate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compounds is their 318),
N-(3-methylbut-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 319),
N-(4-hydroxyben-2-enyloxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 320),
N-cyclopentyloxy-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 321),
N-cyclooctylamino-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 322),
N-(2-cyclohexylmethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 323),
N-(2-methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 324),
N-(4-methylcyclohexylamine)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 325),
N-(4-methoxycyclohexyl)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 326),
N-(3-methylbicyclo[2.2.1]hept-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 327),
N-(bicyclo[2.2.1]hept-5-ene-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 328),
tert-butyl ether benzyl-(2-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}cyclohexyl)carbamino acid (compound 329),
N-(2-benzylaminocyclohexanemethanol)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 330),
N-(3-propyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 331),
N-(3-pentyl-4,5-dihydroisoxazole-5-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 332),
4-methyl-N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 333),
N-(5-cyano-2-methox is benzyloxy)-2-[(pyridine-4-ylmethyl)amino]nicotinamide (compound 334),
2 benzylamino-N-benzyloxy-nicotinamide (compound 335),
2 benzylamino-N-(4-methoxybenzyloxy)nicotinamide (compound 336),
N-benzyloxy-2-(2-chlorobenzylamino)nicotinamide (compound 337),
2-(2-chlorobenzylamino)-N-(4-methoxybenzyloxy)nicotinamide (compound 338),
N-benzyloxy-2-(2,4-dichloraniline)nicotinamide (compound 339),
2-(3,5-dichloraniline)-N-(4-methoxybenzyloxy)nicotinamide (compound 340),
N-benzyloxy-2-(2-methoxybenzylamine)nicotinamide (compound 341),
2-(2-methoxybenzylamine)-N-(4-methoxybenzyloxy)nicotinamide (compound 342),
N-benzyloxy-2-(2-pyridin-4-ylethylamine)nicotinamide (compound 343),
tert-butyl ether 4-{[3-(4-methoxybenzyloxy)pyridine-2-ylamino]methyl}piperidine-1-carboxylic acid (compound 345),
N-benzyloxy-5-[(2-benzyloxycarbonylamino)methyl]-2-perbenzoic (compound 346),
N-(2-bromobenzylamine)-2-(3-cyano-4-methoxybenzylamine)benzamide (compound 347),
N-(2-bromobenzylamine)-2-(4-methanesulfonanilide)benzamide (compound 348),
2-[4-(methoxyaminomethyl)benzylamino]-N-(2-methylthiazole-4-ylethoxy)-benzamide (compound 349),
N-(2-bromobenzylamine)-2-[(2,6-dichloropyridine-4-ylmethyl)amino]benzamide (compound 350),
N-benzyloxy-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 351),
N-(2-methylthiazole-4-ylethoxy)-2-[(pyridine-3-ylmethyl)amino]benzamide (compound 352),
N-(2-methylthiazole-ylethoxy)-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 353),
N-benzyloxy-2-[(pyridine-2-ylmethyl)amino]benzamide (compound 354),
N-benzyloxy-2-[(3-bromopyridin-2-ylmethyl)amino]benzamide (compound 355),
2-[(3-bromopyridin-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 356),
N-(2,4-dichloraniline)-2-[(2,6-dimethoxypyrimidine-4-ylmethyl)amino]benzamide (compound 357),
N-benzyloxy-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 358),
N-(2,4-dichlorobenzyl)-2-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]benzamide (compound 359),
N-benzyloxy-2-[(1-methyl-1H-imidazol-2-ylmethyl)amino]benzamide (compound 360),
2-[(1-methyl-1H-imidazol-2-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 361),
N-benzyloxy-2-[(3-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 362),
2-[(3-methyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 363),
N-benzyloxy-2-[(5-methyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 364),
2-[(5-methyl-3 H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 365),
2-[(2-ethyl-3H-imidazol-4-ylmethyl)amino]-N-(2-methylthiazole-4-ylethoxy)benzamide (compound 366),
N-benzyloxy-2-[(2-ethyl-3H-imidazol-4-ylmethyl)amino]benzamide (compound 367),
N-(2,5-dichloraniline)-2-[(5-oxopyrrolidin-2-ylmethyl)amino]benzamide (compound 368),
N-benzyloxy-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 369),
-benzyloxy-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 370),
ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 371),
ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 372),
ethyl ester 5-[(2-benzyloxycarbonylamino)methyl]-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 373),
N-(4-cyanobenzyl)-2-[(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 374),
N-(4-cyanobenzyl)-2-[(3-ethyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 375),
N-(4-cyanobenzyl)-2-[(3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 376),
ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-methyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 377),
ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-ethyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 378),
ethyl ester 5-{[2-(4-cyanobenzylidene)phenylamino]methyl}-3-propyl-4,5-dihydroisoxazole-5-carboxylic acid (compound 379),
N-(4-cyanobenzyl)-2-[(3-methylisoxazol-5-ylmethyl)amino]benzamide (compound 380),
N-(4-cyanobenzyl)-2-[(3-utilization-5-ylmethyl)amino]benzamide (compound 381),
N-(4-cyanobenzyl)-2-[(3-propylenoxide-5-ylmethyl)amino]benzamide (compound 382),
N-(4-cyanobenzyl)-2-[(3,5-DIMET the l-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 383),
N-(4-cyanobenzyl)-2-[(3-ethyl-5-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 384),
N-(4-cyanobenzyl)-2-[(5-methyl-3-propyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 385),
N-benzyloxy-2-[(3-methyl-4,5-dihydroisoxazole-5-ylmethyl)amino]benzamide (compound 386),
N-(4-cyanobenzyl)-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 387),
N-cyclopentyloxy-2-[2-(3-methyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 388),
N-(4-cyanobenzyl)-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 389),
N-cyclopentyloxy-2-[2-(3-ethyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 390),
N-(4-cyanobenzyl)-2-[2-(3-propyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 391),
N-cyclopentyloxy-2-[2-(3-propyl-4,5-dihydroisoxazole-5-yl)ethylamino]benzamide (compound 392),
N-benzyloxy-2-[2-(2,4-dioxo-imidazolidin-1-yl)ethylamino]benzamide (compound 393),
N-benzyloxy-2-[(6-chloroimidazo[2,1-b]thiazole-5-ylmethyl)amino]benzamide (compound 395),
N-benzyloxy-2-[(2-methylimidazo[1,2-a]pyrimidine-3-ylmethyl)amino]benzamide (compound 396),
N-benzyloxy-2-(2-benzyloxyaniline)benzamide (compound 397),
N-(2-benzyloxycarbonyl)isonicotinamide (compound 398),
N-benzyloxy-2-(2-pyridin-4-yl-acetylamino)benzamide (compound 399),
N-benzyloxy-N-methyl-2-[(pyrid is n-4-ylmethyl)amino]benzamide (compound 400),
N-(5-oxopyrrolidin-2-ylethoxy)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 402),
tert-butyl ether 4-{2-[(pyridine-4-ylmethyl)amino]benzylaminocarbonyl}piperidine-1-carboxylic acid (compound 403),
N-cyclopentyloxy-2-{[6-(cyclopropanecarbonyl)pyridine-3-ylmethyl]amino}benzamide (compound 404),
N-cyclopentyloxy-2-[(6-pyrrolidin-1-yl-pyridine-3-ylmethyl)amino]benzamide (compound 405),
2-[(6-aminopyridine-3-ylmethyl)amino]-N-(4-cyanobenzyl)benzamide (compound 406),
N-(4-cyanobenzyl)-2-[(6-pyrrolidin-1-yl-pyridine-3-ylmethyl)amino]benzamide (compound 407),
N-cyclopentyloxy-2-{[2-(cyclopropanecarbonyl)-4-methylthiazole-5-ylmethyl]amino}benzamide (compound 408),
2-[(6-aminopyridine-3-ylmethyl)amino]-N-Cyclopentasiloxane (compound 409),
N-[3-(2,2-dibromovinyl)cyclopentyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 410),
N-(3-hydroxymethylcellulose)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 411),
N-(2-hydroxyethylacrylate)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 412),
N-[4-(4-methylpiperazin-1-ylmethyl)benzyloxy]-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 413),
N-{4-[4-(2-hydroxyethyl)piperazine-1-ylmethyl]benzyloxy}-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 414),
N-(4-cyanobenzyl)-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (connect the tion 415),
N-(4-cyanobenzyl)-2-{[2-(3-ethylurea)pyridine-4-ylmethyl]amino}benzamide (compound 416),
N-cyclopentyloxy-2-{[2-(3-isopropylamino)pyridine-4-ylmethyl]amino}benzamide (compound 417),
N-cyclopentyloxy-2-{[2-(3-propylurea)pyridine-4-ylmethyl]amino}benzamide (compound 418),
N-cyclopentyloxy-2-{[2-(3-ethylurea)pyridine-4-ylmethyl]amino}benzamide (compound 419),
N-(3-hydroxycyclopent)-2-[(pyridine-4-ylmethyl)amino]benzamide (compound 420),
N-cyclopentyloxy-2-{[2-(3-methylthiourea)pyridine-4-ylmethyl]amino}benzamide (compound 421),
2-{[2-(3-tert-butylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 422),
N-(4-cyanobenzyl)-2-{[2-(3-cyclohexylurea)pyridine-4-ylmethyl]amino}benzamide (compound 423),
2-{[2-(3-cyclohexylurea)pyridine-4-ylmethyl]amino}-N-Cyclopentasiloxane (compound 424),
N-{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}isonicotinamide (compound 425),
1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid{4-[(2-cyclopentanecarbonyl phenylamino)methyl]pyridine-2-yl}amide (compound 426),
(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide 1-(2,2,2-TRIFLUOROACETYL)pyrrolidin-2-carboxylic acid (compound 427),
{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide 1-acetylpiperidine-4-carboxylic acid (compounds is of 428),
(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide 1-acetylpiperidine-4-carboxylic acid (compound 429),
N-cyclopentyloxy-2-[(2,4-dihydroxypyrimidine-5-ylmethyl)amino]benzamide (compound 430),
(4-{[2-(4-cyanobenzylidene)phenylamino]methyl)pyridine-2-yl)amide, pyrrolidin-2-carboxylic acid (compound 431),
{4-[(2-cyclopentanecarbonitrile)methyl]pyridine-2-yl}amide pyrrolidin-2-carboxylic acid (compound 432) and 2-[(pyridine-4-ylmethyl)amino]-N-(4-vinylbenzoate)benzamide (compound 433).

25. Pharmaceutical composition having inhibitory activity of receptor tyrosine kinase in respect of the receptor KDR, comprising the compound according to any one of claims 1 to 24 or its pharmaceutically acceptable salt, hydrate or MES, an effective amount, together with a pharmaceutically acceptable carrier or excipient.

26. The composition according A.25, in which the amount of active ingredient is from about 0.1 to 99.9 wt.% song.

27. The composition according to p. 25 or 26, which is in the form of standard dosage forms containing the active ingredient in amounts of from 0.01 to 10,000 mg

28. The compound according to any one of claims 1 to 24, possessing inhibitory activity of receptor tyrosine kinase in respect of the receptor KDR, for use as an active ingredient in therapy.

29. Connection Ljubo is in one of claims 1 to 24 for receiving the medicinal product, with regulating angiogenesis properties.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: compounds of formula (I) as inhibitors of phosphotyrosine phosphotase 1B and their pharmaceutically acceptable salts, their application, based pharmaceutical composition and method of production. In general formula (I) , R1 indicates phenyl, naphthyl, thionaphthyl, pyridyl. Phenyl, naphthyl, thionaphthyl and pyridyl can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, CF3, OCF3, N(R9)(R10), piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, NO2, CN, O-(C1-C6)-alkyl, S(O)0-2-(C1-C6)-alkyl, SO2-N(R9)(R10), CO-(C1-C6)-alkyl, -COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkyleny-COO(C1-C6)-alkyl, (C3-C10)-cycloalkyl, phenyl. These piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, and phenyl rings can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, COOH, CN, NO2, O-(C1-C6)-alkyl, -NH-O-(C1-C6)-alkyl, -(CO)-NH-O-(C1-C6)-alkylene-N(R9)(R10), -(CO)-(C1-C6)-alkyl, -(C1-C6)-alkyl, CF3, OCF3, N(R9)(R10); R2 indicates H, (C1-C6)-alkyl, COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkylene-COO(C1-C6)-alkyl; R3 indicates H, (C1-C6)-alkyl, (C1-C6)-alkylenphenyl, -C(O)-phenyl, (C1-C6)-alkylenheterocycle, where heterocycle represents 5-6-merous heterocyclic ring containing 1-2 heteroatoms, chosen of nitrogen and oxygen, CO-(C1-C6)alkyl; R4, R5 indicate H; R6 indicates H, R9 indicates H, (C1-C4)-alkyl; R10 indicates H, (C1-C4)-alkyl.

EFFECT: applications for treating diseases mediated with phosphotyrosine phosphotase 1B activity, such as diabetes type II, lipidosis and carbohydrate metabolic imbalance, insulin resistivity, reduced sugar content in blood.

9 cl, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: there is disclosed compounds of formula II , where each R2 independently stands for H, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO2; each W and X independently represents C or N; n is within 0 to 4 if both W and X represent C, 0 to 3, if either X or W represent N, and 0 to 2 if both X and W represent N; R3, R5, R6, R7 are independently chosen from H, alkyl, substituted alkyl, alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo; R4 represents optionally substituted 5-6-merous heteroaryl containing nitrogen atom provided (a) if R4 stands for pyridyl, R4 is not substituted with both hydroxy and methoxy groups; and (b) R4 stands for pyrimidinyl, it is n-substituted =O; A is chosen from following compounds of formula: , where D stands for S or O; m is within 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently chosen from H, halogen, NR30R31, OR32, CO2R33, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R28 and R29 are independently chosen from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl or together they form carbocyclic or heterocyclic ring consisting of 3 to 8 atoms; and R30, R31, R32, R33 and R36 are independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl as pharmaceutical composition for cancer treatment containing compound of formula II.

EFFECT: production of new compounds and based pharmaceutical composition applied for cancer treatment.

18 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to the method of producing compounds with formula I and to their pharmaceutical salts. In formulae I, II, IV, V: R1 or R2 represent H, -(CH2)t(5-member heterocyclic compound), where t equals 4 and where the heterocyclic compound contains one nitrogen atom as the heteroatom, R3 is -(CH2)t(C6-C10aryl), where t equals 1. The given R3 groups are optionally substituted with 3 R4 groups. Each R4 is independently chosen from halogen. R8 is C1-C10alkyl, R9 is C1-C10alkyl, and n equals 2.

EFFECT: treatment of hyper-proliferative diseases using new intermediate compounds with formulae II, IV, V.

15 cl, 2 dwg, 11 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and pharmaceutically acceptable salts. Claimed compounds have modulation effect on CB cannabinoid receptor. In the general formula (I) , R and R1 are the same or different and are phenyl optionally substituted by 1-3 substitutes Y, where Y is substitute selected out of group including chlorine, iodine, bromine, fluorine, on condition that X is not a sub-group (ii); or one of R and R1 radicals is phenyl group, while the other radical is formed or linear C2-8-alkyl group or benzyl group; X is one of the sub-groups (i) or (ii). Also invention concerns application of the compounds in obtaining pharmaceutical composition, pharmaceutical composition with modulation effect on CB cannabinoid receptor, and compound of the general formula (IV) with radical values as indicated in the claim.

EFFECT: enhanced efficiency of composition and treatment method.

5 cl, 1 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of treatment, alleviation and/or prevention of neurological state, particularly neurodegenerative disorders, involving administration of effective quantity of compound with formula I: . Also invention concerns application of compound of the formula I as neurotherapeutical, neuroprotective or antimyloid agent, pharmaceutical or veterinary composition for treatment, alleviation and/or prevention of neurological states, and compounds of the formula I on the following additional terms: (b) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not ethyl or methyl; (c) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not hydrogen or ethyl; (d) if R3, R and R' are H, and R2 is NR11R12, then both R11 and R12 are not hydrogen; (e) if R3, R and R' are H, and R2 is COR6, then R6 is not H, OH or CH2Cl; (f) if R3, R and R' are H, and R2 is not CH3 or CH2Cl; (g) if R3, R and R' are H, and R2 is HCNN R9R10, then both R9 and R10 are not H.

EFFECT: efficient treatment, alleviation and prevention of neurological state.

24 cl, 14 tbl, 21 ex, 14 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) , where R1 is phenyl optionally substituted by halogen, cyano, C1-4alkyl or C1-4haloalkyl; R2 is hydrogen, C1-6alkyl or C3-6cycloalkyl; and R3 is a group with NH or OH and calculated or measured pKa from 1.0 to 8.0, selected out of: 2-oxo-thiazol-5-yl with C1-4fluoroalkyl, optionally substituted phenyl group, optionally substituted heterocyclyl group or CH2S(O)2(C1-4alkyl) group in position 4; 2-oxo-oxazol-5-yl with C1-4fluoroalkyl or CH2S(O)2(C1-4alkyl) in position 4; 1H-1,2,3-triazol-4-yl with C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), NHS(O)2(C1-4alkyl), N(C1-4alkyl)S(O)2(C1-4alkyl), phenyl group, heterocyclyl group or CH2S(O)2C1-4alkyl) group in position 5; 4-oxo-1H-1,4-dihydropyridine-3-yl with C1-4fluoroalkyl in position 2; 2,6-dioxo-1H-1,2,3,6-tetrahydropyrimidine-4-yl with C1-4alkyl, C3-6cycloalkyl or CH2(C1-3fluoroalkyl) in position 3 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with C1-4fluoroalkyl, cyano or phenyl in position 2 and/or in position 5 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with CH2CO2H at ring nitrogen atom and optionally substituted in one or more other ring positions; 2H-tetrazol-5-yl; CO2H, CH2CO2H or OCH2CO2H group at optionally substituted phenyl, optionally substituted CH2O phenyl or optionally substituted naphtyl ring or optionally substituted acylated dihydroisoquinolinyl ring; or group NHS(O)2(C1-4alkyl) at optionally substituted aromatic heterocyclic ring; or their tautomer where possible; in indicated positions where heterocyclyl ring in R3 can be optionally substituted, it can be optionally substituted by fluoro, chloro, bromo, C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), cyano, S(O)2(C1-4alkyl); in indicated positions where phenyl or naphtyl ring in R3 can be optionally substituted, it can be optionally substituted by halogen, cyano, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, OCF3, SCF3, nitro, S(C1-4alkyl), S(O)(C1-4alkyl), S(O)2(C1-4alkyl), S(O)2NH(C1-4alkyl), S(O)2N(C1-4alkyl)2, NHC(O)(C1-4alkyl) or NHS(O)2(C1-4alkyl); or its pharmaceutically acceptable salts. Also invention concerns compounds of formula (I), method of obtaining compounds of any of claims 1-12, as well as pharmaceutical composition.

EFFECT: obtaining novel bioactive compounds with chemokine receptor activity modulation effect.

16 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula I: , where L represents radical , in which R1 represents H, C1-4alkyl; n represents 0 or 1; or L represents radical , in which R1 represents H, C1-4alkyl; m equals 1; R represents H, halogen, C1-C4alkyl or C1-C4-alkoxy; Z represents a bond, -C(O)NH-, O or S; p is an integer from 1 to 5; Q represents a bond with the condition that, Z is not a bond, when p equals 1; or represents O, S or -C(O)NR6-, where R6 represents H, C1-4alkyl or C3-6cycloalkyl; or W and R6 together with a nitrogen atom, to which they are bonded, form or or Q represents -NR6-, or in the condition that, p is not equal to 1; W represents , , , , ,

, , ,

, , ,

, , , ,

, , , ,

, , , ,

, , , , ,

, , , , , and

.

EFFECT: obtaining compounds with agonistic activity towards PPAR receptors, which enables them to be used in pharmaceutical compositions and methods of treating conditions, mediated by these receptors.

12 cl, 7 ex

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel compounds of formula I: , where M is macrolide subunit of substructure II: , L is chain of substructure III: -X1-(CH2)m-Q-(CH2)n-X2-, D is steroid or non-steroid subunit derived from steroid or non-steroid NSAID medicines (nonsteroid anti-inflammatory drug) with anti-inflammatory effect; pharmaceutically acceptable salts and solvates of claimed compounds; methods and intermediary compounds for obtainment of claimed compounds.

EFFECT: improved therapeutic effect, application in inflammatory disease and state treatment for humans and animals.

37 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compound represented by formula I, where R1 and R2 are similar or different and each represents: (I) C1-10alkyl group optionally substituted with 1-3 substituents selected from C3-10cycloalkyl group, C1-6alkoxycarbonyl group b C1-6alkoxygroup; (2) C6-14aryl group optionally substituted with 1-3 substituents selected from halogen atom, carboxyl group, C1-6alkoxycabonyl group b carbamoyl group; or (3) C7-13aralkyl group; R3 represents C6-14aryl group optionally substituted with 1-3 substituents selected from C1-6alkyl group, optionally substituted with 1-3 halogen atoms, halogen atom, C1-6alkoxycarbonyl group, carboxyl group, hydroxy group, C1-6alkoxygroup, optionally substituted with 1-3 halogen atoms; R4 represents amino group; L represents C1-10alkylene group; Q represents bond, C1-10alkylene group or C2-10alkenylene group; and X represents: (1) hydrogen atom; (2) cyanogroup; (3) (3a) carboxyl group; (3b) carbamoyl group; and further as presented in invention formula. Invention also describes medication for treating diabetes, peptidase inhibitor, application of formula I compound, method of prevention or treatment of diabetes, method of peptidase inhibiting and method of obtaining formula I compounds.

EFFECT: obtaining novel compounds which have peptidase-inhibiting activity and are useful as medication for prevention and treatment of diabetes.

16 cl, 433 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new 2-pyridone derivatives of formula (I): where R1, R2, R4, R5, G1, G2, L, Y and n are as specified in the invention formula, and their pharmaceutically acceptable salts, pharmaceutical compositions containing these compounds, and their application in therapy. These compounds have neutrophil elastase inhibition effect.

EFFECT: new compounds with useful biological properties.

7 cl, 1 tbl, 150 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I), their isomers and pharmaceutically acceptable salts. In the general formula (I) A is (II) ; X1 is methylene; X2 is CN, CHO, C(O)R6; X6 is a link; R1 is R13C(O)-; R2 is hydrogen; R3 is selected out of group including H, phenyl-(C0-6)alkyl, (C1-6)alkyl, optionally substituted by -X6OR9 group; R4 is H or (C1-6)alkyl; or R3 and R4 form (C3-8)cycloalkylene together with carbon atom to which R3, R4 are linked; R5 is (C1-9)alkyl, benzyl. Invention also concerns compounds of formulae (la), (lb), (Ic), and pharmaceutical composition based on the claimed compounds.

EFFECT: new compounds inhibiting cathepsin.

22 cl, 2 dwg, 89 ex

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of obtaining heterocycles of formula I , where X, A, R10-R17 are as defined in point 1 of the claim, while a) isothiocyanate of formula II is transformed into thiourea of formula IV by interaction with primary amine of formula III, and b) thiourea of formula IV is transformed into compound of formula I by interaction with sulfochloride R6SO2Cl in the presence of a base, where A, X, n, m and R10 to R17 in compounds of formulae II, III and IV are as defined in formula I, and R6 is (C1-C4)-alkyl, trifluoromethyl or phenyl non-sustituted or substituted by methyl, trifluoromethyl, F, CI, Br or polymer carreir. The transportation is shown by combination formulae

EFFECT: new multipurpose synthesis technique for heterocyclic compounds of the general formula I.

8 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with general formula I, where R1 represents -(CHR')q-aryl or -(CHR')q-thiophen, which are unsubstituted or mono-, di- or tri-substituted with (inferior)alkyl, (inferior)alkoxy, CF3 or haloid, or represents (inferior)alkyl, (inferior)alkenyl, -(CH2)n-Si(CH3)3, -(CH2)n-O-(inferior)alkyl, -(CH2)n-S- (inferior)alkyl, -(CH2)q-cycloalkyl, -(CH2)n-[CH(OH)]m-(CF2)p-CHqF(3-q), or represents -(CH2)n-CR2-CF3, where two radicals R together with a carbon atom form a cycloalkyl ring; R' represents hydrogen or (inferior)alkyl; n is 1, 2 or 3; m is 0 or 1; p is 0, 1,2, 3, 4, 5 or 6; q is 0, 1, 2 or 3; R2 represents hydrogen or (inferior)alkyl; R3 represents hydrogen, (inferior)alkyl, CH2F, aryl, optionally mono-, di- or tri-substituted with a haloid, or represents -(CH2)nNR5R6, where R5 and R6 independently represent hydrogen or (inferior)alkyl; R4 represents one of the following groups a) or b), where R7 represents inferior)alkyl or -(CH2)ncycloalkyl; R8 and R9 independently represent hydrogen, (inferior)alkyl, -(CH2)n-cycloalkyl or -C(O)-phenyl. The invention also relates to pharmaceutically used acid addition salts of these compounds, optically pure enantiomers, racemates or diastereomeric mixtures, as well as compounds with general formula I-1, and medicinal agent.

EFFECT: obtaining new biologically active compounds, designed for inhibiting γ-secretase.

16 cl, 83 ex

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