Derivatives of N - (amino - (hetero) aryl) - 1H - pirrolopiridin - 2 - carboxamidas, their preparation, Intermediates for Synthesis, which includes a Pharmaceutical Composition and its use in the manufacture of medicaments for the treatment of diseases mediated by the TRPV1 receptor type.

摘要

1.1.1.1. Preparation and implementation procedures for the treatment of TRPV1 receptor transmitted diseases. 1: A reaction formula compound (1), wherein the pyridyl is a pyridyl [3, 2-B] pyridyl, a pyridyl [3, 2-C] pyridyl, a pyridyl [2, 3-C] pyridyl or a pyridyl [2, 3-B] pyridyl; the pyridyl is a pyridyl, which may be substituted in normal carbon of 4, 5, 6 and / or 7. Or several identical or different x substitutes selected from one hydrogen or halogen atom or C1-6 tar group, cyclopropyl compound c3-7, cyclopentanediol c3-7-tar C1-6, C1-6 fluorocarbon and C1-6 fluorocarbon C1-6,Cyclocycloxyl c3-7, cycloquil c3-7-tar c1-6-o -,C1-6 fluoroalkoxy, cyano, C1-6 thioalkyl, -S (O) -C1-6 alkyl, -S (O) 2 C1-6 alkyl, SF5, C (O) NR1R2, SO2NR1R2, nitro, NR1R2, OCONR1R2, NR3COR4 , NR3CONR1R2, NR3SO2R5, NR3SO2NR1R2, aryl-C1-6 alkylene, C1-6 heteroaryl-alkylene, aryl or heteroaryl, the aryl and heteroaryl being optionally substituted with one or more substituents chosen from a halogen, a C1-6 alkyl group, C3-7 cycloalkyl, C3-7 cycloalkyl-C 1-6 alkylene, C 1-6 fluoroalkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, nitro or cyano; n is equal to 0, 1, 2 or 3; Y represents an aryl or a heteroaryl,If arilo or heteromorphism is eventually replaced by one or more groups, they shall be selected from one halogenated atom or one C1-6 tar group, cyclopropyl compound c3-7, cyclopropyl calcium c3-7-tar C1-6, c1-6-fluoropropyl compound, hydroxy group, c1-6-hydroxy group, C1-6, cyclopropane c3-7, cyclopropyl calcium c3-7-c1-6-o-tar group,C1-6 fluoroalkoxy, cyano, C1-6 thioalkyl, thiol, -S (O) -C1-6 alkyl, -S (O) 2-C1-6 alkyl, C (O) NR1R2, SO2NR1R2, SF5, nitro, OCONR1R2 , NR3COR4, NR3CONR1R2, NR1R2, NR3SO2NR1R2, NR3COR4, NR3SO2R5, C 1-6 aryl-alkylene, or aryl, with aryl and C 1-6 aryl alkylene optionally substituted with one or more substituents chosen from a halogen, a C 1 alkyl group -6, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkylene, C1-6 fluoroalkyl, C1-6 alkoxy, C1-6 fluoroalkoxy, nitro or cyano; Z1, Z2, Z3, Z4 represent, independently of each other, a nitrogen atom or a group C (R6),1. Containing at least one nitro atom and at least one group C (R6);When the nitration atom or a nitration atom appears in the cycle, it is defined as the nitration of positive 1, and finally replaced by R7, when the carbon atom is in the position of 2 or 4 in this reference nitration, it is replaced by an oxo or tertiary group; Z represents a ring amine connected by atoms 2. A represents a c1-7 tar group, which is finally replaced by one or two R8 groups; B represents a c1-7 tar group, which is finally replaced by one or two R9 groups; l represents a link, which is a sulfur, oxygen or nitrogen atom;The nitrobenzene atom is finally replaced by R10 or R11 group; the carbon atom of periodic imine Z is finally replaced by one or more same or different R12 groups; or the ammonia of an acylica is connected by the nitrobenzene atom represented by nrab and Rb, A hydrogen atom or a group of C1-6, cycloquilo c3-7, cycloquil c3-7-tar C1-6, C1-6 fluorocarbon, hydroxy, C1-6 alcoxilo C1-6, cycloquil c3-7-tar c1-6-o -.C1-6 Fluoroalkane, c1-6-c (o) tar,HO-C (O) -C 1-6 alkylene, C 1-6 alkyl-OC (O) -C 1-6 alkylene, aryl or heteroaryl, where Ra and Rb may eventually be substituted with one or more identical or different Rc groups from one another ; Rc represents a halogen atom, a C1-6 alkyl group, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkylene, C1-6 fluoroalkyl, C1-6 alkoxy, C3-7-cycloalkyl-C1-6-O alkylene -C1-6 fluoroalkoxy, C1-6 thioalkyl, -S (O) -C1-6 alkyl, -S (O) 2-C1-6 alkyl, cyano, C (O) NR1R2, NR1R2, SO2NR1R2, NR3COR4, NR3SO2R5, OC (O) NR1R2, NR3COOR5, NR3CONR1R2, NR3SO2NR1R2, hydroxyl, thiol, oxo, thio, C1-6 aryl-alkylene, aryl or heteroaryl, the aryl and heteroaryl being optionally substituted with one or more substituents chosen from a halogen, a group C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-6 alkylene, C 1-6 fluoroalkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, nitro or cyano; R1 and R2 represent, independently of one another, a hydrogen atom or a C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkylene, aryl-C1-6 alkylene group,1. Arilo or heterosexual, plus arilo and heterosexual, may be replaced by one or more alternatives selected from halogen, a group of C1-6 tar, cycloquilo c3-7, cycloquil c3-7-tar C1-6, C1-6, alcoxyl C1-6, fluorinated alcoxyl C1-6, nitrate or cyanogen; or R1 and R2 are formed together with nitrogen atoms. It is replaced by a group of Azerbaijanis, pyridine insects, pyridinediol, Azerbaijanis, mofulin, thiophosphor, pyridinol, homoacrylonitrile, pyridine, and finally by a group of C1-6 tar, cyclopropyl compound c3-7, cyclopropyl-c3-7-tar C1-6, aril tar, C1-6, arilo or heterogeneous compounds.the aryl and heteroaryl being optionally substituted with one or more substituents selected from a halogen, a C1-6 alkyl group, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkylene, C1-6 fluoroalkyl, C1-6 alkoxy, C1-6 fluoroalkoxy, nitro or cyano; R3 and R4 represent, independently of each other, a hydrogen atom or a C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 cycloalkyl, C1-6 aryl-alkylene, aryl or heteroaryl group, the aryl and heteroaryl optionally substituted with one or more substituents chosen from a halogen, a C1-6 alkyl group, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkylene, C1-6 fluoroalkyl, C1-6 alkoxy,C1-6 fluoroalkoxy, nitro or cyano; or R3 and R4 together form a C2-6 alkylene group; or R1 and R3 together form a C2-5 alkylene group; R5 represents a C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-6, aryl-C1-6 alkylene, aryl or heteroaryl group, the aryl and heteroaryl being optionally substituted with one or more substituents chosen from a halogen, a C 1-6 alkyl group, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-6 alkylene, C 1-6 fluoroalkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, nitro or cyano; or R3 and R5 together form a C2-5 alkylene group; R6 represents a hydrogen or halogen atom or a C1-6 alkyl, C3-7 cycloalkyl group group,Cycloquil c3-7-c1-6, C1-6, C1-6, alcoxyl C1-6, cyclohexyl c3-7, cycloquil c3-7-tar c1-6-o -,C1-6 fluoroalkoxy, C1-6 thioalkyl, -S (O) C1-6 alkyl, -S (O) 2-C1-6 alkyl, hydroxyl, thiol, oxo, thio, aryl, aryl-C1-6 alkylene, heteroaryl the aryl and heteroaryl being optionally substituted with one or more substituents chosen from a halogen, a C1-6 alkyl group, C3-7 cycloalkyl, C3-7 cycloalkyl C1-6 alkylene, C1-6 fluoroalkyl, C1-6 alkoxy , C1-6 fluoroalkoxy, nitro or cyano; R 7 represents a hydrogen atom, a C 1-6 alkyl group, C 3-7 cycloalkyl, C 3-7 cycloalkyl, C 1-6 alkylene, C 1-6 fluoroalkyl, C 1-6 alkoxy, C 3-7 cycloalkoxy, C 3-7 cycloalkyl-alkylene alkyl C1-6-O-,C1-6, arilo, aril tar C1-6 or heterogeneous, plus arilo and heterogeneous, are eventually replaced by one or more alternatives selected from halogen, one C1-6 Cypress oil, one C1-6, cyclopropyl compound c3-7, cyclopropene-c1-6, C1-6 fluorescent oxidant, C1-6, cyanogen nitrate; R8, R9 and R10 are defined as follows: two R8 groups can jointly form a C1-6 link or tar group; two R9 groups can jointly form a link or a C1-6 tar group; R8 and R9 groups can jointly form a C1-6 link or tar group; R8 and R10 groups can jointly form a C1-6 link or tar group;R9 and R10 can together form a bond or a C1-6 alkylene group; R 11 represents a hydrogen atom, a C 1-6 alkyl group, C 3-7 cycloalkyl, C 3-7 cycloalkyl, C 1-6 alkylene, C 1-6 fluoroalkyl, C 1-6 alkoxy, C 3-7 cycloalkoxy, C 3-7 cycloalkyl-alkylene alkyl C1-6-O-,C1-6 halothane, hydroxy, c1-6-co -,3-1-2, C12. It represents a fluorine atom, a C1-6 tar group, which is finally replaced by a nitrogen atom composed of R11, C1-6, cyclopropyl compound c3-7, cyclopropyl alcohol c3-7-tar C1-6, C1-6 fluoropropyl compound, c1-6-1, c1-6-1, 1-diilo cyclopropyl alcohol, c3-7-1, 1-1-diilo, etc., and finally replaced by a nitrogen atom composed of R11, C1-6, cyclopentyl-6, cyclopropyl oxygen c3-7,C3-7-c1-6-o-tar1-1-1-1-1-1, 1-1-1-1-1, 1-1, 1-1, 1-1, 1-1-1 C1-6, alcoxyl C1-6, C1-6, cyclohexyl c3-7, C1-6, nitric acid or cyanogen; R13 represents an ALCOXY C1-6, cyclohexyl c3-7, cycloquil c3-7-c1-6-o -,C (o) nr1r2, nr1r2, nr3cor4, OC (o) nr1r2, nr3cour5, hydroxy; nitrohydrogen atom of a common formula (1) compound containing an oxidized form; base or salt state of an acid; and hydrate or solution state. Comment more than a month ago