RussianPatents.com

Substituted quinoxaline-type piperidine compounds and use thereof
Substituted quinoxaline-type piperidine compounds and use thereof
IPC classes for russian patent Substituted quinoxaline-type piperidine compounds and use thereof (RU 2488585):
Another patents in same IPC classes:
Polycyclic agents for treating respiratory syncytial viral infections Polycyclic agents for treating respiratory syncytial viral infections / 2486185
There are described new polycyclic compounds, pharmaceutically acceptable salts thereof of general formula wherein R1 -phenyl, pyridyl, optionally substituted, or C3-7-cycloalkyl; R2 -H, -CH2R3, -C(=O)R3, -C(=O)N(R4)R3, and -SO2-pyridyl, wherein R3-H, C1-6 alkyl, C2-6 alkenyl, C3-7-cycloalkyl, -(CH2)m-phenyl -(CH2)m-(5-, 6- or 9-member heterocyclyl with 1-3 heteroatoms N, O or S); m is equal to 0-6; R4 -H; X represents O or S; the alkyl, alkenyl, cycloalkyl, phenyl and heterocyclyl groups may be substituted by one or more substitutes. A together with atoms whereto attached forms phenyl or heteroaryl with 1 or 2 nitrogen atoms, optionally substituted; B-C means -CH2-(CH2)z-, wherein z is equal to 1 or 2; D represents -CRIIIRIV-, wherein RIII and RIV are identical, and mean CH3 or H; or RIII and RIV together with the atom C whereto attached form a 3-member cycloalkyl ring, a pharmaceutical composition containing them, and the use of the above compounds for treating viral RSV infections.
1-cyanocyclopropyl derivatives as cathepsin k inhibitors 1-cyanocyclopropyl derivatives as cathepsin k inhibitors / 2470023
Claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.
Heterocyclic compounds as crth2 receptor antagonists Heterocyclic compounds as crth2 receptor antagonists / 2451019
Invention relates to a compound of formula I:
2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors / 2445312
Present invention refers to compounds of general formula (I) or its pharmaceutically acceptable salts which have action of mTOR inhibitors. What is also declared is preparing a pharmaceutical composition containing a therapeutically effective amount of the compound of formula (I) and a pharmaceutically acceptable carrier or diluent; besides, what is declared is the use of the compound of formula (I) or its pharmaceutically acceptable salts for preparing the drug for ensuring anticancer action.
Heterocyclic janus kinase 3 inhibitors Heterocyclic janus kinase 3 inhibitors / 2434013
Invention relates to a compound of formula (I), in which X denotes N or CR3, M denotes (CH2)m; m equals 0 or 1, R1 denotes H or lower alkyl which can be substituted with a group selected from a group consisting of mono- or di-lower alkylamino and -O-lower alkyl, R2 denotes H or lower alkyl, R3 denotes H or lower alkyl substituted with a group selected from a group consisting of halogen, mono- or di-lower alkylamino and cyclic amino, R41 denotes H or pyridine which can be substituted with a cyano group, R42 denotes a bridged polycyclic hydrocarbon or a bridged azacyclic hydrocarbon, each of which can be substituted, R5 denotes a group selected from a group consisting of halogen, cyano, lower alkyl-carbonyl, lower alkyl-oxycarbonyl, hydroxycarbonyl, formyl, amidinooxycarbonyl, guanidinooxycarbonyl, guanidino, carbamoyl, -C(=O)-5- or -6-member heterocycloalkyl, -C(=O)-5- or -6-member heteroaryl, lower alkyl, lower alkenyl, -O-lower alkyl, 5- or 6-member heterocycloalkyl and 5-member heteroaryl, each of which can be substituted, provided that when R5 denotes a 5-member heteroaryl, X denotes -CR3; or R41 and R15 can be bonded through a defined functional group to form divalent groups shown below: (I-A) (I-B) or (I-C), in which RA denotes H or acyl, which can be substituted, provided that the term "substituted" with respect to R4 and/or R5 denotes substitution with one or more substitutes selected from a group comprising the following substitutes: (a). halogen; (b) -OH, -O-R2, -O-phenyl, -OCO-RZ-OCONH-RZ oxo (=O); (c) -SH, -S-R2, -S-phenyl, -S-heteroaryl, -SO-R2, -SO-phenyl, -SO-heteroaryl, -SO3H, -SO2-RZ, -SO2-phenyl, - SO2-heteroaryl, sulphamoyl, which can be substituted with one or two RZ groups; (d) amino, which can be substituted with one or two RZ groups, -NHCO-RZ, -NHCO-phenyl, -NHCO2-RZ, -NHCONH2, -NHCONH-RZ, -NHSO2-R0, -NHSO2-phenyl, -NHSO2NH2, -NO2, =N-O-RZ; (e) -CHO, -CO-RZ, -CO2H, -CO2-RZ, carbamoyl, which can be substituted with one or two RZ groups, -CO-cyclic amino, -COCO-RZ, cyano; (f) RZ; (g) phenyl, which can be substituted with one or more groups selected from substitutes described above in paragraphs from (a) to (f), a 5- or 6-member heterocycloalkyl, a 5- or 6-member heteroaryl, a 5- or 6-member heterocycloaryl; or pharmaceutically acceptable salts thereof. The invention also relates to a method of producing compounds of formula II, a pharmaceutical composition based on said compounds which is a Janus kinase 3 inhibitor, a method of treating and/or preventing different immunopathological diseases, including autoimmune diseases, inflammatory diseases and allergic diseases.
Polycyclic agents for treating respiratory syncytial viral infections Polycyclic agents for treating respiratory syncytial viral infections / 2422444
Invention refers to compounds of formula (I) where values of the substitutes are disclosed in the patent claim.
Pyrimidobenzimidazole derivatives and application thereof as agonists or antagonists of melanocortin receptors Pyrimidobenzimidazole derivatives and application thereof as agonists or antagonists of melanocortin receptors / 2392279
Invention refers to novel compounds with affinity to MC4 receptors, of the general formula (I): , where A is -CH2- or -C(O)-; R1 is (C1-C8)alkyl; R2 is (C1-C8)alkyl; R3 is radical of the formula -(CH2)s-R'3; R'3 is 5-6-member heterocycloalkyl containing one or two nitrogen atoms and possibly one oxygen atom possibly substituted with (C1-C6)alkyl or benzyl; or radical of the formula -NW3W'3; W3 is hydrogen atom or (C1-C8)alkyl; W'3 is radical of the formula -(CH2)s'-Z3; Z3 is hydrogen atom, (C1-C8)alkyl; s and s' are independently an integer within 0 to 6; B is 5-6-member monocyclic unsaturated, aromatic or non-aromatic radical which can be condensed with 5-6-member unsaturated, aromatic or non-aromatic radical forming bicyclic condensed system, and B is possibly containing one or more equal or different heteroatoms selected out of O, S and N, and possibly substituted with one or more equal or different radicals selected out of halogen atom, nitro group, cyano group, oxy group, -XB-YB and phenyl possibly substituted with one substitute selected out of halogen atom and (C1-C6)alkyl; XB is a covalent bond, -O-, -S-, -C(O)-, -C(O)-O-; YB is (C1-C6)alkyl; or pharmaceutically acceptable salt of claimed compounds.
Tetrahydro-pyrazolo[1,5-a]pyrido-pyrimidines - serotonin 5-ht<sub>6</sub> receptor antagonists, methods of producing and using said compounds Tetrahydro-pyrazolo[1,5-a]pyrido-pyrimidines - serotonin 5-ht6 receptor antagonists, methods of producing and using said compounds / 2391343
Present invention relates to serotonin 5-HT6 receptor antagonists - new substituted 3-sulphonyl-6,7,8,9-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-e]pyrimidines of formula and substituted 3-sulphonyl-5,6,7,8-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-c1]pyrimidines of general formula 2, a medicinal base and pharmaceutical compositions containing the medicinal base in form of the said compounds, as well as to a method of treating and preventing development of different conditions and diseases of the central nervous system of humans and warm-blooded animals. In formulae and Ar is phenyl which is optionally substituted with halogen atoms, or a 6-member heteroaryl which contains a nitrogen atom in the ring; R1 is a hydrogen atom, C1-C3alkyl, hydroxy C1-C3alkyloxy group, C1-C3alkylsulphanyl group; R2 is a hydrogen atom or C1-C3alkyl, R3 is a hydrogen atom optionally substituted C1-C3alkyl or tert-butyloxycarbonyl.
Hepatitis c virus replication inhibitor Hepatitis c virus replication inhibitor / 2387655
Invention relates to compounds of formula (I) and their pharmaceutically acceptable salts of formula (I) where n equals 0, 1 or 2, A is a five- or six-member aromatic ring which optionally contains one or two heteroatoms independently selected from nitrogen, oxygen or sulphur, B is a 5-9-member ring containing 0 or 1 double bonds and optionally contains an additional heteroatom selected from nitrogen and oxygen; where the ring optionally contains one or two substitutes independently selected from a group comprising C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkyl, carboxy, cyano, hydroxy, hydroxy-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, (NR4R5)-carbonyl or oxo; R1 is selected from -C(O)NR4R5 - CO2R4, 5-tetrazolyl, cyano; each R2 is independently selected from a group comprising C1-C6-alkyl, amino, benzyloxy, halogen, hydroxyl; R3 is a 5-7-member cycloalkyl ring; values of the rest of the radicals are given in the formula of invention. The invention also relates to a method for synthesis of the said compounds, a method of inhibiting HCV replicon function and a method of inhibiting functioning of the HCV NS5B protein.
Substituted 2-amino-3-sulfonyl-tetrahydro-pyrazolo[1,5-a]pyrido-pyrimidines-antagonists of serotonin 5-ht<sub>6</sub> receptors, methods of producing and using said compounds Substituted 2-amino-3-sulfonyl-tetrahydro-pyrazolo[1,5-a]pyrido-pyrimidines-antagonists of serotonin 5-ht6 receptors, methods of producing and using said compounds / 2384581
Invention relates to novel antagonists of serotonin 5-HT6 receptors - substituted 2-amino-3-sulfonyl-6,7,8,9-tetrahydro-pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines of general formula 1 and substituted 2-amino-3-sulfonyl-5,6,7,8-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines of general formula 2 or their pharmaceutically acceptable salts and/or hydrates, method of producing said compounds and pharmaceutical compositions, medicinal agents and treatment method. In compounds of formula 1 and general formula 2 , Ar is phenyl which is possibly substituted with halogen atoms, or a 6-member nitrogen-containing heteroaryl; R1 is a hydrogen atom, C1-C3alkyl which is possibly substituted with phenyl, C1-C5alkoxycarbonyl; R2 is a hydrogen atom, halogen or C1-C3alkyl; R1 3 and R2 3 are optionally identical substitutes selected from a hydrogen atom, optionally substituted C1-C3alkyl or R1 3 and R2 3 together with the nitrogen atom with which they are bonded form a nitrogen-containing 6-member saturated heteroaryl optionally substituted with C1-C5alkoxycarbonyl, where the said heteroaryl has 1-2 heteroatoms selected from nitrogen.
Azaadamantane derivatives and methods for applying Azaadamantane derivatives and methods for applying / 2450002
Invention refers to azaadamantane derivatives of formula (I), to their pharmaceutically acceptable salts possessing the properties of nAChR ligands, their application, a method of treating and based pharmaceutical compositions, and also to intermediate compounds of formula (VI) and (VII) and to application of the compound of formula (V) for preparing the compound (I). In general formulas
2-aminobenzoxazole carboxamides as 5-ht3 modulators 2-aminobenzoxazole carboxamides as 5-ht3 modulators / 2448105
Invention relates to compounds of general formula where R1, R2 and R3 are independently selected from a group consisting of hydrogen, halogen and lower alkyl containing 1-6 carbon atoms; R4 denotes a residue given in the claim; R5 denotes hydrogen or methyl; R10 is selected from a group consisting of: (i) hydrogen; (ii) (C1-C10) alkyl; (iii) (C1-C10)alkyl, substituted with one or more substitutes independently selected from a group consisting of -N(CH3)2, morpholinyl, (C1-C4) alkoxy, hydroxyl, -CON(CH3)2 and halogen; (iv) monocyclic (C3-C8) cycloalkyl containing one N heteroatom; (v) 9-methyl-9-azabicyclo[3.3.1]nonane; (vi) phenyl; (vii) phenyl substituted with one or more (C1-C4)alkoxy; R11 is selected from a group consisting of hydrogen and (C1-C10)alkyl; or R10, R11 and a nitrogen atom with which they are bonded, together, form a nitric heterocycle or a substituted nitric heterocycle, such as given in the claim. The invention also relates to a pharmaceutical composition, having serotonin type 3 receptor modulating capacity and a method of treating a disorder which depends on serotonin type 3 receptor modulation.
Azabicyclic alkane derivatives substituted with condensed bicycloheterocycle Azabicyclic alkane derivatives substituted with condensed bicycloheterocycle / 2437884
Invention relates to azabicyclic alkane derivatives which are substituted with a condensed bicycloheterocycle of formula or pharmaceutically acceptable salt thereof, ester, amide or prodrug, where n equals 1, 2 or 3; A denotes N or N+-O-; R denotes hydrogen, alkyl, cycloalkylalkyl and arylalkyl; L is selected from a group consisting of O, S and -N(Ra)-; Ar1 denotes a 6-member aryl or a 6-member heteroaryl; and Ar2 denotes a bicyclic heteroaryl; and Ra is selected from a group consisting of hydrogen, alkyl and alkylcarbonyl; provided that if Ar1 is represented by formula then L denotes O or S; compositions containing such compounds, and methods of treating conditions and disorders using said compounds and compositions.
The method of obtaining pure enantiomers esters (+) or (-) tropovoy acid with aminoalcohols The method of obtaining pure enantiomers esters (+) or (-) tropovoy acid with aminoalcohols / 2162850
The invention relates to a method for producing the intermediate product to obtain with antiholinergicescuu activity of substances derived tropovoy acid, more specifically to a method of obtaining pure enantiomers esters (+) or (-) tropovoy acid with aminoalcohols
Esters taylorbow acids and aminoalcohols, method of their production and a pharmaceutical composition having anticholinergic activity Esters taylorbow acids and aminoalcohols, method of their production and a pharmaceutical composition having anticholinergic activity / 2073677
The invention relates to new esters of carboxylic acids with valuable properties, in particular the esters taylorbow acids and aminoalcohols of General formula (I)
< / BR>
where a group
< / BR>
where m and n are independent of each other represent 1 or 2,
Q group of formulae
< / BR>
Q' группаNR, where R denotes hydrogen or alkyl with 1 to 4 carbon atoms, unsubstituted or substituted with halogen or hydroxyl, or a group NRR', where R' is alkyl with 1 to 4 carbon atoms, or R and R' together form alkylene with 4 to 6 carbon atoms, and in the case of the fourth connection to the positive charge of the nitrogen atom is the equivalent of the anion (X),,
R1thienyl, phenyl, furyl, cyclopentyl and cyclohexyl, unsubstituted or substituted stands, and thienyl and phenyl may be substituted by fluorine or chlorine,
R2hydrogen, alkoxy 1 to 4 carbon atoms or alkyl with 1 to 4 carbon atoms,
Rahydrogen, fluorine, chlorine or methyl, provided that when a represents 3-tropanol, R1hydroxyl and R
2-aminobenzoxazole carboxamides as 5-ht3 modulators 2-aminobenzoxazole carboxamides as 5-ht3 modulators / 2448105
Invention relates to compounds of general formula where R1, R2 and R3 are independently selected from a group consisting of hydrogen, halogen and lower alkyl containing 1-6 carbon atoms; R4 denotes a residue given in the claim; R5 denotes hydrogen or methyl; R10 is selected from a group consisting of: (i) hydrogen; (ii) (C1-C10) alkyl; (iii) (C1-C10)alkyl, substituted with one or more substitutes independently selected from a group consisting of -N(CH3)2, morpholinyl, (C1-C4) alkoxy, hydroxyl, -CON(CH3)2 and halogen; (iv) monocyclic (C3-C8) cycloalkyl containing one N heteroatom; (v) 9-methyl-9-azabicyclo[3.3.1]nonane; (vi) phenyl; (vii) phenyl substituted with one or more (C1-C4)alkoxy; R11 is selected from a group consisting of hydrogen and (C1-C10)alkyl; or R10, R11 and a nitrogen atom with which they are bonded, together, form a nitric heterocycle or a substituted nitric heterocycle, such as given in the claim. The invention also relates to a pharmaceutical composition, having serotonin type 3 receptor modulating capacity and a method of treating a disorder which depends on serotonin type 3 receptor modulation.
Heterocyclic janus kinase 3 inhibitors Heterocyclic janus kinase 3 inhibitors / 2434013
Invention relates to a compound of formula (I), in which X denotes N or CR3, M denotes (CH2)m; m equals 0 or 1, R1 denotes H or lower alkyl which can be substituted with a group selected from a group consisting of mono- or di-lower alkylamino and -O-lower alkyl, R2 denotes H or lower alkyl, R3 denotes H or lower alkyl substituted with a group selected from a group consisting of halogen, mono- or di-lower alkylamino and cyclic amino, R41 denotes H or pyridine which can be substituted with a cyano group, R42 denotes a bridged polycyclic hydrocarbon or a bridged azacyclic hydrocarbon, each of which can be substituted, R5 denotes a group selected from a group consisting of halogen, cyano, lower alkyl-carbonyl, lower alkyl-oxycarbonyl, hydroxycarbonyl, formyl, amidinooxycarbonyl, guanidinooxycarbonyl, guanidino, carbamoyl, -C(=O)-5- or -6-member heterocycloalkyl, -C(=O)-5- or -6-member heteroaryl, lower alkyl, lower alkenyl, -O-lower alkyl, 5- or 6-member heterocycloalkyl and 5-member heteroaryl, each of which can be substituted, provided that when R5 denotes a 5-member heteroaryl, X denotes -CR3; or R41 and R15 can be bonded through a defined functional group to form divalent groups shown below: (I-A) (I-B) or (I-C), in which RA denotes H or acyl, which can be substituted, provided that the term "substituted" with respect to R4 and/or R5 denotes substitution with one or more substitutes selected from a group comprising the following substitutes: (a). halogen; (b) -OH, -O-R2, -O-phenyl, -OCO-RZ-OCONH-RZ oxo (=O); (c) -SH, -S-R2, -S-phenyl, -S-heteroaryl, -SO-R2, -SO-phenyl, -SO-heteroaryl, -SO3H, -SO2-RZ, -SO2-phenyl, - SO2-heteroaryl, sulphamoyl, which can be substituted with one or two RZ groups; (d) amino, which can be substituted with one or two RZ groups, -NHCO-RZ, -NHCO-phenyl, -NHCO2-RZ, -NHCONH2, -NHCONH-RZ, -NHSO2-R0, -NHSO2-phenyl, -NHSO2NH2, -NO2, =N-O-RZ; (e) -CHO, -CO-RZ, -CO2H, -CO2-RZ, carbamoyl, which can be substituted with one or two RZ groups, -CO-cyclic amino, -COCO-RZ, cyano; (f) RZ; (g) phenyl, which can be substituted with one or more groups selected from substitutes described above in paragraphs from (a) to (f), a 5- or 6-member heterocycloalkyl, a 5- or 6-member heteroaryl, a 5- or 6-member heterocycloaryl; or pharmaceutically acceptable salts thereof. The invention also relates to a method of producing compounds of formula II, a pharmaceutical composition based on said compounds which is a Janus kinase 3 inhibitor, a method of treating and/or preventing different immunopathological diseases, including autoimmune diseases, inflammatory diseases and allergic diseases.
Indazole-carboxamide compounds Indazole-carboxamide compounds / 2404179
Invention relates to novel indazole-carboxamide compounds of formula ,
Azacyclic compounds to be used in treating serotonin-mediated diseases Azacyclic compounds to be used in treating serotonin-mediated diseases / 2398765
Invention refers to new compounds of formula (I) , where Z means where R means hydrogen, C4-C6cycloalkyl group attached either through one of ring carbon atoms, or through a lower alkylene group attached to the ring, or a linearly chained or branched lower alkyl group or a lower hydroxyalkyl group, or a lower aminoalkyl group, or a phenyl(lower alkyl) group optionally substituted with 1-2 substitutes chosen from lower alkyl, lower alkoxy, halogen and hydroxy, or heteroaryl(lower alkyl)group where heteroaryl is chosen from the group consisting from thienyl, substituted with lower alkyl group, imidazolyl, and thiazolyl substituted with the lower alkyl group; n means 0 or 1; or Z means a group where R means the lower alkyl group; X1 means methylene or NH group; and X2 means methylene; or X1 means methylene and X2 means methylene or a bond; or X1 means methylene, and X2 means O, S or a bond; Y1 means methylene, and Y2 means methylene, vinylene, ethylene, or a bond; Ar1 means unsubstituted or substituted phenyl; Ar2 means unsubstituted or substituted phenyl, unsubstituted or substituted thienyl, unsubstituted or substituted furyl, unsubstituted or substituted pyridyl; and when Ar1 and Ar2 are substituted, each Ar1 and Ar2 are independently substituted with one or more substituted chosen from lower alkyl, lower alkoxy, hydroxy, lower hydroxyalkyl, halogen, di- and trihaloalkyl, di- and trihaloalkoxy, mono- and dialkylamino, alkilthio, alkyl ester and nitro; provided that Ar1 and Ar2 do not simultaneously mean unsubstituted phenyl; W means oxygen or sulphur; or to their pharmaceutically acceptable salts; provided those specified in cl. 1 of the patent claim. Besides the invention concerns the compounds chosen from the group, to compounds of formula (I), to pharmaceutical compositions, to a method of inhibition of monoamine receptor activity, to a method of inhibition of monoamine receptor activation, to a method of treating a diseased state associated with serotonin receptor, to a method of treating schizophrenia, to a method of treating migraine, and also to a method of treating psychosis.
Quinolinone-carboxamide compounds as agonists of 5-ht<sub>4</sub> receptors Quinolinone-carboxamide compounds as agonists of 5-ht4 receptors / 2394033
In new compounds of the formula R1 represents hydrogen, halogen; R2 represents C3-4 alkyl, or C3-6 cycloalkyl; R3 represents hydrogen or C1-3 alkyl; R4 represents -S(O)2R6, or -C(O)R7; R5 represents hydrogen, C1-3 alkyl, C2-3 alkyl substituted with -OH or C1-3alkoxy, or -CH2-pyridyl; R6 represents C1-3 alkyl, or R5 and R6 taken together form a C3-4 alkylenyl; and R7 represents hydrogen, C1-3 alkyl or pyridyl; or their pharmaceutically acceptable salts or solvates or stereoisomers. The invention also refers to pharmaceutical composition, to compounds application, to method for treating mammals, to method for treating disorders of reduced motor activity of gastrointestinal tract in a mammal, to method for obtaining compounds according to any of Clauses 1-12, to method for obtaining compounds of formula (I'), as well as to compounds of formula (III).

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted quinoxaline-type piperidine compounds of formula or to a pharmaceutically acceptable derivative thereof, wherein: Y1 represents O; Q is specified in condensed benzo or pyridino; each R2 is independently specified in: (a) -halogen or -CN; (b) -(C1-C6)alkyl; a is an integer specified in 0, 1 or 2; a dash line in a 6-member ring containing a nitrogen atom which is condensed with Q group means the presence or absence of a bond, and when the dash line means the absence of the bond, then R3, and one R4 are absent; R3 is specified in: (a) -H; each R4 is independently specified in: (a) -H; or (b) - halogen or CN; or (c) -X, -(C1-C6)alkyl-X, -(5- or 6-member)heterocyclyl-X or -(5- or 6-member)heterocyclyl-(C1-C6)alkyl-X; or (d) -C(=Y)X, -C(=Y)T3, -C(=Y)YX, - C(=Y)YT3, -C(-Y)N(T1)(T2), -C(=Y)N(R9)CN, -C(=Y)N(R9)X, -C(=Y)N(R9)YH, -C(=Y)N(R9)YX, -C(=Y)N(R9)YCH2X, -C(-Y)N(R9)YCH2CH2X or -C(=Y)N(R9)S(K))2T3; or (e) -N(R9)X, -N(R9)-CH2X, -N(R9)-CH2CH2X, -N(R9)CH2N(R9)C(=N(R12))N(R12)2, -N(R9)-CH2CH2N(R9)C(=N(RI2))N(R12)2, -N(T1)(T2), -N(T3)C(=Y)T3, -N(T3)C(=Y)YT3, -N(T3)C(=Y)N(T1)(T2), -N(T3)S(=O)2T3 or -N(T3)S(=O)2N(T1)(T2); X represents: (a) -H, -( C1-C6)alkyl, -(C2-C6)alkenyl, -(C1-C6)alkoxy, -(C3-C7)cycloalkyl, -(5- or 6-member)heterocycle or -(7-10-member)bicycloheterocycle each of which is unsubstituted or substituted with 1, 2 or 3 of optionally substituted R8 groups; or (b) -phenyl, -naphthalenyl, or -(5- or 6-member)heteroaryl each of which is unsubstituted or substituted with 1 or 2 of independently specified in R7 groups; each Y is independently specified in O; A and B are independently specified in: (a) -H; or (c) A-B together can form a (C2-C6)bridge each can optionally contain -HC=CH- or -O- in a (C2-C6)bridge; wherein the 6-member ring containing a nitrogen atom which is condensed with Q group can be found in the endo- or exo- configuration in relation to the A-B bridge; or (d) A-B together can form the -CH2-N(Ra)-CH2- bridge wherein the 6-member ring containing a nitrogen atom is condensed with Q group, and can be found in the endo- or exo- configuration in relation to the A-B bridge; Ra is specified in -H or -(C1-C6)alkyl; Z represents -[(C1-C10)alkyl optionally substituted with R1]h-, wherein h is equal to 0 or 1; each R1 is independently specified in: (b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl3 -(C3-C7)cycloalkoxy, -(C6-C14)bicycloalkyl, -(C8-C10)tricycloalkyl, -(C5-C10)cycloalkenyl, -(C7-C14)bicycloalkenyl, -(3-7-member)heterocyclyl each of which is unsubtituted or substituted with 1, 2 or 3 of independently specified in R8 groups;

or or (d) -phenyl, -naphthalenyl each of which is unsubstituted or substituted with R7 group; each R6 is optionally specified in -H; each R7 is independently specified in -(C1-C4)alkyl, -OR9, -C(halogen)3, -CH(halogen)2, -CH2(halogen), -CN, -halogen, -N(R9)2, -C(=O)OR9; each R8 is independently specified in -(C1-C4alkyl, tetrzolyl, imidazolyl, furanyl, -(C1-C6)alkylCOOR9, -OR9, -SR9, -C(halogen)3, -CH(halogen)2, -CH2(halogen), -CN, =O, -halogen, -N(R9)(C1-C6)alkylCOOR9, -N(R9)2, -N(R9)S(=O)2R12, -N(R9)C(=O)R12, -N(R9)C(=O)OR12, -C(=O)R9, -C(=O)N(T1)(T2), -C(=O)OR9, -OC(=O)R9, or -S(=O)2R9; each R9 is independently specified in -H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -phenyl, -benzyl, -(5- to 6-member)heterocycle, -C(halogen)3; -CH(halogen)2 or -CH2(halogen); if h is equal to O, then R11 can be specified in -H, -C(=O)OR9 or -C(=O)N(R6)2 or R11 can be -(C1-C4)alkyl; if h is equal to 1, then R11 can be specified in -H; each R12 is independently specified in -H or -(C1-C4)alkyl; m is equal to an integer specified in 3, 4, 5, 6, 7, 8 or 9; each e and f is equal to an integer independently specified in 0 or 1, provided 2≤(e+f)≤5; each j and k is equal to an integer independently specified in 0 or 1, provided 1≤(j+k)≤4; each p is equal to an integer independently specified in 0 or 1; each T1, T2, and T3 is independently specified in -H or -(C1-C10)alkyl which is unsubstituted or substituted with 1, 2 or 3 from independently specified R8 groups, or T1 and T2 together can form 5- to 8-member ring wherein the number of ring atoms contains a nitrogen atom wherein T1 and T2 are bound; the above 5- to 8-member ring is unsubstituted or substituted with 1, 2 or 3 from independently specified R8 groups and optionally any carbon atom in the above 5- to 8-member ring is independently substituted with O or N(R6); each halogen is independently specified in -F, -CI, -Br or -I.

EFFECT: invention refers to the intermediate compounds of formula

, , for preparing the above compounds of formula (II), compositions containing the above compounds and to a method of treating or preventing a diseased state, such as a pain.

36 cl, 58 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of Formula (II):

or its pharmaceutically acceptable derivative, where:
Y1represents O;
Q is chosen from condensed benzo or pyridine;
each R2independently chosen from:
(a) -halogen, or-CN;
(b) -(C1-C6)alkyl;
and is an integer selected from 0, 1 or 2;
the dashed line in 6-membered ring containing the nitrogen atom of the ring, which is condensed with the Q group, means the presence or the absence of communication, and when the dashed line indicates the presence of communication, then R3and one of R4no;
R3choose from:
(a) -H;
each R4independently chosen from:
(a) -H; or
(b) -halogen, or CN; or
(c) -X -(C1-C6)alkyl-X -(5 - or 6-membered)heterocycle-X or -(5 - or 6-membered)heterocycle-(C1-C6)alkyl-X; or
(d) -C(=Y)X, -C(=Y)T3, -C(=Y)YX, -C(=Y)YT3, -C(=Y)N(T1)(T2),
-C(=Y)N(R9)CN, -C(=Y)N(R9)X, -C(=Y)N(R9)YH, -C(=Y)N(R9)YX,
-C(=Y)N(R9)YCH2X, -C(-Y)N(R9)YCH2CH2X or-C(=Y)N(R9)S(=O)2T3; or
(e) -N(R9)X, -N(R9)-CH2X, -N(R 9)-CH2CH2X, -N(R9)CH2N(R9)C(=N(R12))N(R12)2, -N(R9)-CH2CH2N(R9)C(=N(R12))N(R12)2, -N(T1)(T2), -N(T3)C(=Y)T3, -N(T3)C(=Y)YT3, -N(T3)C(=Y)N(T1)(T2), -N(T3)S(=O)2T3or-N(T3)S(=O)2N(T1)(T2);
X represents:
(a) -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C1-C6)alkoxy, -(C3-C7)cycloalkyl, -(5 - or 6-membered)heterocycle, or -(7-10-membered)bicycloheptadiene, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups; or
(b) -phenyl, -naphthalenyl or(5 - or 6-membered)heteroaryl, each of which is unsubstituted or substituted with 1 or 2 independently selected R7groups;
each Y is independently selected from Oh;
A and b independently chosen from:
(a) -H; or
(c) a-b can together form a (C2-C6)bridge, which optionally contains-HC=CH - or-O - (C2-C6)bridge; where the 6-membered ring containing the nitrogen atom of the ring is condensed with the Q group can be in the endo - or ectocervical relative to the a-b bridge; or
(d) a-b can together form a-CH2-N(Ra)-CH2-bridge,
where the 6-membered ring containing the nitrogen atom concealed condensed with Q group, can be in the endo - or ectocervical relative to the a-b bridge;
Raselected from-H or -(C1-C6)alkyl;
Z represents -[(C1-C10)alkyl, optionally substituted R1]h-where h is 0 or 1;
each R1independently chosen from:
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)quinil, -(C3-C7)cycloalkane -(C6-C14)bicycloalkyl -(C8-C10)tricyclohexyl -(C5-C10)cycloalkenyl -(C7-C14)bicycloalkyl, -(3-7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups; or
,or; or
(d) -phenyl, -naphthalenyl, each of which is unsubstituted or substituted with R7group;
each R6independently selected from-H;
each R7independently selected from -(C1-C4)alkyl, -OR9-C(halogen)3, -CH(halogen)2, -CH2(halogen), -CN, -halogen, -N(R9)2, -C(=O)OR9;
each R8independently selected from -(C1-C4)alkyl, tetrazolyl, imidazolyl, furanyl, -(C1-C6)COOR9, -OR9, -SR9-C(halogen)3, -Is n(halogen) 2, -CH2(halogen), -CN, =O, -halogen, -N(R9)(C1-C6)COOR9, -N(R9)2, -N(R9)S(=O)2R12, -N(R9)C(=O)R12, -N(R9)C(=O)OR12, -C(=O)R9, -C(=O)N(T1)(T2), -C(=O)OR9, -OC(=O)R9or-S(=O)2R9;
each R9independently selected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -phenyl, -benzyl, -(5 - to 6-membered)heterocycle, -C(halogen)3, -CH(halogen)2or-CH2(halogen);
if h is 0, then R11can be selected from-H, -C(=O)OR9or-C(=O)N(R6)2or R11may be -(C1-C4)alkyl;
if h is 1, then R11can be selected from-H;
each R12independently selected from-H or -(C1-C4)alkyl;
m is an integer selected from 3, 4, 5, 6, 7, 8 or 9;
each of e and f is an integer independently selected from 0 or 1, provided that 2≤(e+f)≤5;
each of j and k is an integer independently selected from 0 or 1, provided that 1≤(j+k)≤4;
each p is an integer independently selected from 0 or 1;
each T1, T2and T3independently represents-H or -(C1-C10)alkyl, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups, or T1and T2together OBRAZOVATEL 5 - to 8-membered ring, in which the number of atoms in the ring includes the nitrogen atom to which T1and T2related specified from 5 - to 8-membered ring is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and optionally, any carbon atom in the specified from 5-to 8-membered ring is independently replaced by O or N(R6);
each halogen is independently selected from-F, -Cl, -Br or-I,
where -(5 - or 6-membered)heteroaryl means a monocyclic aromatic heterocyclic ring containing 5 or 6 members, where at least one carbon atom is replaced by a heteroatom independently selected from nitrogen and oxygen;
where -(5 - or 6-membered)heterocycle means a 5 - or 6-membered monocyclic heterocyclic ring which is saturated, where the 5-membered heterocycle can contain up to 2 heteroatoms and 6-membered heterocycle can contain up to 2 heteroatoms where each heteroatom independently selected from nitrogen and oxygen;
where -(3 - to 7-membered)heterocycle means a 3 - to 7-membered monocyclic heterocyclic ring which is saturated, and where the 3-membered heterocycle can contain up to 1 heteroatom, 4-membered heterocycle can contain up to 1 heteroatom, a 5-membered heterocycle can contain up to 1 heteroatom, a 6-membered heterocycle can contain up to heteroatom, and where each heteroatom independently selected from nitrogen and oxygen;
where -(7 - to 10-membered)bicycloheptadiene means from 7 - to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated non-aromatic and contains from 1 to 2 heteroatoms independently selected from nitrogen and oxygen;
and the pharmaceutically acceptable derivative is selected from the group consisting of pharmaceutically acceptable salts of MES, radioactively labelled compound, stereoisomer, enantiomer, diastereoisomer, racemic mixture, geometric isomer, and/or tautomer.

2. The compound of Formula (II):

or its pharmaceutically acceptable derivative,
where Y1represents About;
Q is chosen from condensed benzo or pyridine;
each R2independently chosen from:
(a) -halogen, or-CN;
(b) -(C1-C6)alkyl;
and is an integer selected from 0, 1 or 2;
the dashed line in 6-membered ring containing the nitrogen atom of the ring, which is condensed with the Q group, means the presence or the absence of communication, and when the dashed line indicates the presence of communication, then R3and one of R4no;
R3choose from:
(a) -H;
each R4independently chosen from:
(a) -H; or
(b) -halogen, or CN; or
(c) -X -(C -C6)alkyl-X -(5 - or 6-membered)heterocycle-X or -(5 - or 6-membered)heterocycle-(C1-C6)alkyl-X; or
(d) -C(=Y)X, -C(=Y)T3, -C(=Y)YX, -C(=Y)YT3, -C(=Y)N(T1)(T2), C(=Y)N(R9)CN, -C(=Y)N(R9)X, -C(=Y)N(R9)CH2CH2N(T1)(T2), -C(-Y)N(R9)YH, -C(=Y)N(R9)YX, -C(=Y)N(R9)YCH2X, -C(-Y)N(R9)YCH2CH2X or-C(=Y)N(R9)S(=O)2T3; or
(e) -N(R9)X, -N(R9)-CH2X, -N(R9)-CH2CH2X, -N(R9)-CH2CH2N(R9)X, -N(R9)-CH2CH2N(T1)(T2), -N(R9)CH2C(=Y)X, -N((C1-C6)alkyl-C(=O)OR9)2, -N(R9)CH2N(R9)C(=N(R12))N(R12)2, -N(R9)-CH2CH2N(R9)C(-N(R12))N(R12)2, -N(T1)(T2), -N(T3)C(=Y)T3, -N(T3)C(=Y)YT3, -N(T3)C(=Y)N(T1)(T2), -N(T3)S(=O)2T3or-N(T3)S(=O)2N(T1)(T2);
X represents:
(a) -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C1-C6)alkoxy, -(C3-C7)cycloalkyl, -(5 - or 6-membered)heterocycle, or -(7 - to 10-membered)bicycloheptadiene, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups; or
(b) -phenyl, -benzyl-naphthalenyl or(5 - or 6-membered)heteroaryl, ka is each of which is unsubstituted or substituted with 1 or 2 independently selected R 7groups;
each Y is independently selected from Oh;
A and b independently chosen from:
(a) -H; or
(c) a-b can together form a (C2-C6)bridge, which optionally contains-HC=CH - or-O - (C2-C6)bridge; where the 6-membered ring containing the nitrogen atom of the ring is condensed with the Q group can be in the endo - or ectocervical relative to the a-b bridge; or
(d) a-b can together form a-CH2-N(Ra)-CH2-bridge,
where the 6-membered ring containing the nitrogen atom of the ring is condensed with the Q group can be in the endo - or ectocervical relative to the a-b bridge;
Raselected from-H or -(C1-C6)alkyl;
Z represents -[(C1-C10)alkyl, optionally substituted R1]h-where h is 0 or 1; or[(C2-C10)alkenyl, optionally substituted R1]-;
each R1independently chosen from:
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)quinil, -(C3-C7)cycloalkane, -(C6-C14)bicycloalkyl, -(C8-C10)tricyclohexyl, -(C5-C10)cycloalkenyl, -(C7-C14)bicycloalkyl, -(C8-C20)tricyclodecane, -(3-7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2 or 3 independently from the curse of R 8groups; or
,or; or
(d) phenyl or-naphthalenyl, each of which is unsubstituted or substituted with R7group;
each R6independently selected from-H;
each R7independently selected from -(C1-C4)alkyl, -OR9-C(halogen)3, -CH(halogen)2, -CH2(ganagana), -CN, -halogen, -N(R9)2or-C(=O)OR9;
each R8independently selected from -(C1-C4)alkyl, tetrazolyl, imidazolyl, furanyl, -phenyl, -(C1-C6)COOR9, -OR9, -SR9-C(halogen)3, -CH(halogen)2, -CH2(halogen), -CN, =O, -halogen, -N(R9)(C1-C6)COOR9, -N(R9)2, -N(R9)S(=O)2R12, -N(R9)C(=O)R12N(R9)C(O)OR12, -C(=O)R9; -C(=O)OR9, -C(=O)N(T1)(T2), -C(=O)OR9, -OC(=O)R9or-S(=O)2R9;
each R9independently selected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -phenyl, -benzyl, -(3 - to 6-membered)heterocycle, -C(halogen)3, -CH(halogen)2or-CH2(halogen);
if h is 0, then R11can be selected from-H, -C(=O)OR9or-C(=O)N(R6)2or R11may be -(C1-C4)alkyl;
if h 1, then R11can be selected from-H;
each R12independently selected from-H or -(C1-C4)alkyl;
m is an integer selected from 3, 4, 5, 6, 7, 8 or 9;
each of e and f is an integer independently selected from 0 or 1, provided that 2≤(e+f)≤5;
each of j and k is an integer independently selected from 0 or 1, provided that 1≤(j+k)≤4;
each p is an integer independently selected from 0 or 1;
each T1, T2and T3independently represents-H or -(C1-C10)alkyl, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups or T1and T2may together form a 5 - to 8-membered ring, in which the number of atoms in the ring includes the nitrogen atom to which T1and T2related specified from 5 - to 8-membered ring is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and optionally, any carbon atom in the specified from 5-to 8-membered ring is independently replaced by O or N(R6);
each halogen is independently selected from-F, -Cl, -Br or-I;
provided that if Z is a -[(C1-C10)alkyl, optionally substituted R1]hand h=0, then R4is not COOH,
where -(5 - or 6-membered)heteroaryl means monocyclic aromatic heterocyclics the second ring, containing 5 or 6 members, where at least one carbon atom is replaced by a heteroatom independently selected from nitrogen and oxygen;
where -(5 - or 6-membered)heterocycle means a 5 - or 6-membered monocyclic heterocyclic ring which is saturated, where the 5-membered heterocycle can contain up to 2 heteroatoms and 6-membered heterocycle can contain up to 2 heteroatoms where each heteroatom independently selected from nitrogen and oxygen;
where -(3 - to 7-membered)heterocycle means a 3 - to 7-membered monocyclic heterocyclic ring which is saturated, and where the 3-membered heterocycle can contain up to 1 heteroatom, 4-membered heterocycle can contain up to 1 heteroatom, a 5-membered heterocycle can contain up to 1 heteroatom, a 6-membered heterocycle can contain up to 1 heteroatom, and where each heteroatom independently selected from nitrogen and oxygen;
where -(7 - to 10-membered)bicycloheptadiene means from 7 - to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated non-aromatic and contains from 1 to 2 heteroatoms independently selected from nitrogen and oxygen;
and the pharmaceutically acceptable derivative is selected from the group consisting of pharmaceutically acceptable salts of MES, radioactively labeled with the unity, stereoisomer, enantiomer, diastereoisomer, racemic mixture, geometric isomer, and/or tautomer.

3. The compound according to claim 1 or 2, where the dotted line is present, one of R4present and preferably R3is missing.

4. The compound according to any one of claims 1 to 3, where Q is chosen from benzo and pyridine, where preferably the 2 - and 3-position pyridinone condensed 6-membered nitrogen-containing ring, and most preferably Q represents anthropo.

5. The compound according to any one of claims 1 to 4, where a is a 0.

6. The compound according to any one of claims 1 to 5, where each R4independently chosen from:
(a) -C(=Y)YX, where preferably each Y is O, and preferably X represents-H or -(C1-C6)alkyl; or
(b) -N(R9)X, where preferably X represents -(C1-C6)alkyl substituted with one R8group, -(5 - or 6-membered)heterocycle, substituted with one R8the group is phenyl, substituted with one R7group or(5 - or 6-membered)heteroaryl substituted with one R7group.

7. The connection according to claim 6, where each R7or R8represents-C(=O)OR9where preferably each R9represents-N.

8. The connection according to claim 6, where R4represents-C(=O)OH, and preferably R4represents-C(=O)HE.

9. With the Association according to claim 6, where R4represents-N(H)X, where X represents -(5 - or 6-membered)heterocycle, substituted with one R8group, where R8represents-C(=O)OR9preferably R8represents-C(=O)HE and preferably R8attached to X the position of the ring or ortho or meta with respect to the place of attachment of X to the N of the group-N(H)X.

10. The connection according to claim 6, where R4represents-N(H)X, where X represents -(C1-C6)alkyl substituted with one R8group, where R8represents-C(=O)OR9and preferably R8represents-C(=O)HE.

11. The compound according to any one of claims 1 to 5, where at least one R4represents -(5 - or 6-membered)heterocycle-X, where X represents phenyl or 5 - or 6-membered)heteroaryl, each of which is substituted with one R7group, preferably where R7represents-C(=O)OR9where preferably R9represents-H, more preferably R7represents-C(=O)OR9and preferably R7attached to X the position of the ring or ortho or meta with respect to the connection point X K -(5 - or 6-membered)heterocycle group -(5 - or 6-membered)heterocycle-X.

12. The compound according to any one of claims 1 to 5, where at least one R4represents -(5 - or 6-membered)is heterocycl-(C 1-C6)alkyl-X, where X represents phenyl or 5 - or 6-membered)heteroaryl, each of which is substituted with one R7group, preferably where R7represents-C(=O)OR9where preferably R9represents-H, more preferably-C(=O)OR9group attached to the phenyl or 5 - or 6-membered)heteroaryl in the position of the ring or ortho or meta with respect to the place of attachment of the phenyl or 5 - or 6-membered)heteroaryl to (C1-C6)alkyl group,- (5 - or 6-membered)heterocycle-(C1-C6)alkyl-X.

13. The compound according to any one of claims 1 to 5, where each R4independently selected from X, where at least one X represents -(5 - or 6-membered)heterocycle, or -(5 - or 6-membered)heteroaryl, each of which is optionally substituted by-C(=O)OR9where preferably R9represents-H, more preferably-C(=O)OR9group attached to the -(5 - or 6-membered)heterocycle, or -(5 - or 6-membered)heteroaryl in the position of the ring or ortho or meta with respect to the place of connection -(5 - or 6-membered)heterocycle, or -(5 - or 6-membered)heteroaryl to 6-membered ring containing the nitrogen atom of the ring, which is condensed with the Q group.

14. The connection indicated in paragraph 13, where at least one X represents-tetrazolyl.

15. Connection and any the claims 1 to 14, where each of a and b represents-N.

16. The compound according to any one of claims 1 to 14, where a and b together form a bridge so that the bridge piperidine selected from the group consisting of:
,,,,,
,,,,,
or,
where each Rdindependently selected from-H.

17. The compound according to any one of claims 1 to 14 and 16, where a and b together form a bridge so that the bridge piperidine selected from the group consisting of:
or
and where the 6-membered ring containing the nitrogen atom of the ring is condensed with the Q group is andconfiguration in relation to And In the bridge of the bridged piperidine.

18. The compound according to any one of claims 1 to 17, where h is 0 and R1represents -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)quinil, -(C6-C12)cycloalkyl, -(C5-C10)cycloalkenyl, -(C6-C14)bicycloalkyl, -(C7-C14)bicycloalkyl or -(C8-C10)tricyclohexyl, each of which is unsubstituted or is umestnim with 1, 2 or 3 independently selected R8groups and preferably R1represents -(C6-C12)cycloalkyl, -(C5-C10)cycloalkenyl, -(C6-C14)bicycloalkyl, -(C7-C14)bicycloalkyl or -(C8-C10)tricyclohexyl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups.

19. The compound according to any one of claims 1 to 18, where h is 0 and R1selected from the group consisting of:
or.

20. The compound according to any one of claims 1 to 18, where h 0 and Ri are selected from the group consisting of:
,,,
,,
or
where each Rzindependently selected from-H, -(C1-C4)alkyl, -HE and-CN, and preferably each R7independently selected from-H and-CH3more preferably, h is 0 and R1selected from the group consisting of:
,or,
where each Rzindependently selected from-H, -(C1-C4)alkyl, -HE and-CN, and preferably each Rzindependently selected from-H and-CH 3most preferably, h is 0 and R1is:
,
where each Rzrepresents-N.

21. The compound according to any one of claims 1 to 4, where a is 1 and R2represents a halogen, preferably R2is a F.

22. The compound according to any one of claims 1 to 18, 20 and 21, where R1the group is ectocervical in relation to And In the bridge of the bridged piperidine.

23. The compound according to any one of claims 1 to 17, where-Z-R1choose from:
(a) (C6-C12)cycloalkyl, where preferably-Z-R1represents cyclooctyl, cycloneii, cyclodecyl, cyclodecyl or cyclododecyl; or
(b) (C5-C10)cycloalkenyl, where preferably-Z-R1represents cyclohexenyl, cycloheptenyl or cyclooctyl; or
(c)
; or
(d) (C6-C12)cycloalkyl, optionally substituted by one or(C1-C4)alkyl.

24. The compound according to any one of claims 1 to 23, where the compound is selected from the group consisting of:
,,,,,
,,,,,
,,,,
,,,,,
and.

25. The compound according to any one of claims 1 to 24, where the pharmaceutically acceptable derivative is a pharmaceutically acceptable salt.

26. The compound according to any one of claims 1 to 25, where the pharmaceutically acceptable derivative is a HCl-salt, sodium salt or potassium salt.

27. A composition comprising an effective amount of a compound or pharmaceutically acceptable derivative of the compound according to any one of claims 1 to 26, and a pharmaceutically acceptable carrier or excipient, for the treatment of pain, memory disorders, obesity, constipation, depression, dementia, Parkinsonism, anxiety, cough, diarrhea, high blood pressure, epilepsy, anorexia/cachexia, urinary incontinence or drug dependency.

28. The method of modulating the functions of the ORL-1 receptor in a cell, comprising contacting cells that can Express the ORL-1 receptor with an effective amount of a compound or pharmaceutically acceptable derivative of the compound according to any one of claims 1 to 26.

29. The method according to p, characterized in that the connection or farmaci is almost acceptable derivative of the compound acts as an agonist against ORL-1 receptor, as a partial agonist in relation to the ORL-1 receptor or antagonist against ORL-1 receptor.

30. A method of treating pain, memory disorders, obesity, constipation, depression, dementia, Parkinsonism, anxiety, cough, diarrhea, high blood pressure, epilepsy, anorexia/cachexia, urinary incontinence or drug dependence in animals, including the introduction of an animal in need, an effective amount of a compound or pharmaceutically acceptable derivative of the compound according to any one of claims 1 to 26.

31. The method of preparation of a composition, comprising the step of mixing the compound or pharmaceutically acceptable derivative of the compound according to any one of claims 1 to 26, and a pharmaceutically acceptable carrier or excipient.

32. The compound of Formula (III), (IV) or (V):

or their pharmaceutically acceptable derivative, where:
A and b of the Formula (V) is independently chosen from:
(a) -H;
Z represents -[(C1-C10)alkyl, optionally substituted R1]h-where h is 0 or 1; or[(C1-C10)alkenyl, optionally substituted R1]each Y is selected from O;
R1choose from
(a) -(C1-C10)alkyl, (C1-C10)alkyl selected from the group comprising ethyl, n-propyl, n-butyl, n-pentyl, n-Gex is l, n-heptyl, n-octyl, n-nonyl, n-decyl, -ISO-propyl, sec-butyl, -ISO-butyl, tert-butyl, -ISO-pentyl-neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-etylhexyl, 2-etylhexyl, 3-etylhexyl, 4-etylhexyl, 5-methylhexan, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 3,3-dimethylpentyl, 1,2-dimethylheptyl, 1,3-dimethylheptyl and 3.3-dimethylheptyl, -(C2-C10)alkenyl, -(C2-C10)quinil, -(C3-C7)cycloalkane, -(C6-C14)bicycloalkyl, -(C8-C10)tricyclohexyl, -(C5-C10)cycloalkenyl, -(C7-C14)bicycloalkyl, -(3-7-membered)heterocycle, -(7-10-membered)bicycloheptadiene, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups; or
,or; or
each R6independently selected from-H;
each R8independently selected from -(C1-C4)alkyl, tetrazolyl, imidazolyl, furanyl, -(C1-C6)COOR9, -OR9, -SR9-C(halogen)3, -Is n(halogen) 2, -CH2(halogen), -CN, =O, -halogen, -N(R9)(C1-C6)COOR9, -N(R9)2, -N(R9)S(=O)2R12, -N(R9)C(=O)R12, -N(R9)C(=O)OR12, -C(=O)R9, -C(=O)N(T1)(T2), -C(=O)OR9, -OC(=O)R9or-S(=O)2R9;
each R9independently selected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -phenyl, -benzyl, -(3 - to 6-membered)heterocycle, -C(halogen)3, -CH(halogen)2or-CH2(halogen);
if h is 0, then R11can be selected from-H, -C(=O)OR9or-C(=O)N(R6)2or R11may be -(C1-C4)alkyl, (C1-C4)alkyl selected from the group consisting of ethyl, n-propyl, n-butyl, -ISO-propyl, sec-butyl, -ISO-butyl and tert-butyl;
if h is 1, then R11can be selected from-H;
each R12independently selected from-H or -(C1-C4)alkyl;
R20choose from the NO2or NH2,
m is an integer selected from 3, 4, 6, 7, 8 or 9;
each of e and f is an integer independently selected from 0 or 1, provided that 2≤(e+f)≤5;
each of j and k is an integer independently selected from 0 or 1, provided that 1≤(j+k)≤4;
each p is an integer independently selected from 0 or 1;
each T1T2and T3independently represents H or -(C 1-C10)alkyl, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups or T1and T2may together form a 5 - to 8-membered ring, in which the number of atoms in the ring includes the nitrogen atom to which T1and T2related specified from 5 - to 8-membered ring is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and optionally, any carbon atom in the specified from 5 - to 8-membered ring is independently replaced by O or N(R6);
each halogen is independently selected from-F, -Cl, -Br or-I,
where -(5 - or 6-membered)heteroaryl means monocyclic aromatic heterocycle ring containing 5 or 6 members where at least one carbon atom is replaced by a heteroatom independently selected from nitrogen and oxygen;
where -(5 - or 6-membered)heterocycle means a 5 - or 6-membered monocyclic heterocyclic ring which is saturated, where the 5-membered heterocycle can contain up to 2 heteroatoms and 6-membered heterocycle can contain up to 2 heteroatoms where each heteroatom independently selected from nitrogen and oxygen;
where -(3 - to 7-membered)heterocycle means a 3 - to 7-membered monocyclic heterocyclic ring which is saturated, and where the 3-membered heterocycle can contain is up to 1 heteroatom, 4-membered heterocycle can contain up to 1 heteroatom, a 5-membered heterocycle can contain up to 1 heteroatom, a 6-membered heterocycle can contain up to 1 heteroatom, and where each heteroatom independently selected from nitrogen and oxygen;
where -(7 - to 10-membered)bicycloheptadiene means from 7 - to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated non-aromatic and contains from 1 to 2 heteroatoms independently selected from nitrogen and oxygen;
and the pharmaceutically acceptable derivative is selected from the group consisting of pharmaceutically acceptable salts of MES, radioactively labelled compound, stereoisomer, enantiomer, diastereoisomer, other stereoisomeric form, racemic mixture, geometric isomer, and/or tautomer.

33. Connection p, where h is 0 and R1represents -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)quinil, -(C6-C12)cycloalkyl, -(C5-C10)cycloalkenyl, -(C6-C14)bicycloalkyl, -(C7-C14)bicycloalkyl or -(C8-C10)tricyclohexyl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and preferably R1represents -(C6-C12)cycloalkyl, -(C 5-C10)cycloalkenyl, -(C6-C14)bicycloalkyl, -(C7-C14)bicycloalkyl or -(C8-C10)tricyclohexyl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups.

34. The compound according to any one of p or 33, where h is 0 and R1selected from the group consisting of:
,,,
,,,
or
where each Rzindependently selected from-H, -(C1-C4)alkyl, -HE and-CN, and preferably each R2independently selected from-H and-CH3preferably h 0 and R1selected from the group consisting of:
,or
where each Rzindependently selected from-H, -(C1-C4)alkyl, -HE and-CN, and preferably each Rzindependently selected from-H and-CH3more preferably, h is 0 and R1is:

where each Rzrepresents-N.

35. The compound according to any one of p or 33, where-Z-R1choose from:
(a) (C6-C12)cycloalkyl, where-Z-R1site which preferably is cyclooctyl, cycloneii, cyclodecyl, cyclodecyl or cyclododecyl; and preferably is a
,
or
(b) (C5-C10)cycloalkenyl, where-Z-R1preferably represents cyclohexenyl, cycloheptenyl or cyclooctyl; and preferably is a

or (C)
or
(d) (C6-C12)cycloalkyl optionally substituted by one or(C1-C4)alkyl, and-Z-R1preferably represents cyclodecyl.

36. The connection 34, where the compound is selected from
,,,,
,or.

 
© 2013-2015 Russian business network RussianPatents.com - Special Russian commercial information project for world wide. Foreign filing in English.