Imidazoles potency of the Tri substituted Compounds, a process for their preparation, Pharmaceutical compositions containing same and use in preparation of drugs for the treatment of diseases mediated by the antagonism of the CCR Receptors

摘要

These antagonistic compounds come from ccr-2 receptor, CCR-5 receptor and / or CCR-3 receptor, which can be used to treat related diseases. They offer ingredients that understand them. Item 1: formula compound (1), in which ring a is a heterocycle, a four to eight atom aromatic free single ring radical, one or two atoms in the ring are nitrogen atoms, and the rest atoms in the ring are carbon atoms; R1 and R2 are independent hydrogen halides, 1. Alcox C1-6, C1-6 tar, C1-6 halogenated tar or C1-6 halogenated ALCOXY; provided that any one between R1 and R2 is not hydrogen;R3 and R4 are independently hydrogen, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy or halogen; R 5 is C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl or C 3-7 cycloalkyl-C 1-6 alkyl; R 6 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 trimethylsilylalkyl, heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-6 hydroxyalkenyl, C 2-6 hydroxyalkynyl, C 1-6 alkoxy-C 2-6 alkenyl , C 1-6 alkoxy-C 2-6 alkynyl, C 2-6 trimethylsilylalkyl, C 2-6 trimethylsilylalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, heteroalkoxy, C 3-7 cycloalkyl optionally substituted, C 3-7 cycloalkyl optionally substituted, halogen, cyano, optionally substituted phenyl,optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted phenyl-methoxy-C 1-6 alkyl; m is 0, 1, 2, 3 or 4; R7 is, when attached to a ring carbon atom, independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2-6 alkyibo, C2-6 hydroxyalkenyl, C2-6 hydroxyalkynyl, alkoxy C1-6 -C2-6 alkenyl, C1-6 alkoxy-C2-6 alkynyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, heteroalkoxy, halogen, cyano, optionally substituted phenyl, optionally substituted C3-7 cycloalkyl, C3 cycloalkyl -7-optionally substituted C1-6 alkyl, optionally substituted heteroaryl,Alternative isocycloacrylic acid C1-6, alternative alternatives, alternative isocycloacrylic acid C1-6, alternative isocycloacrylic acid C1-6, alternative isocycloacrylic acid C1-6, nitrotoluene, thyroid acid, C1-6, carbamate, alternative anakiro C1-6, C1-6, tar, C1-6 asphalt or C1-6 or C1-6 or selectively replace C1-6 asphalt, ISO tar, c3-7 cyclopentadiene, optional alternative and optional ISO cyclohexane with one or two independent substitutes; when combined with cyclic nitrate atom, Independent hydrogenC1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 hydroxy-alkenyl, C2-6 hydroxyalkynyl, C1-6 alkoxy-C2-6 alkenyl, C1-6 alkoxy C2-6, optionally substituted C3-7 cycloalkyl or optionally substituted C3-7 cycloalkyl, optionally substituted heterocyclyl or optionally substituted C1-6 heterocyclyl; provided that ring A contains at least one nitrogen atom, which is not directly linked to a carbonyl group or a heteroatom; and ring A does not contain a nitrogen atom, which is directly attached to a heteroatom; or pharmaceutically acceptable prodrugs or salts thereof. in which,Unless otherwise stated, the term heterocyclic ring refers to the aromatic free single ring radicalism with four to seven atoms in the ring shape. One to three atoms in the ring are heteromorphic atoms, rather than the atoms selected from n, O, s (or) n (where n is an integer of 0 to 2). The rest of the ring primitives refer to c. The term "heteromorphic" refers to the single ring aromatic excitation progress with 5 to 6 atoms in the ring shape, 1 to 3 heteromorphic atoms independently selected from n to s in the ring, and the rest of the ring atoms are C;the term "optionally substituted C3-7cycloalkyl" means a C3-7 cycloalkyl optionally substituted by between one and three substituents independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2 alkynyl -6, C2-6 hydroxyalkenyl, C2-6 hydroxyalkynyl, C1-6 alkoxy-C2-6 alkenyl, C1-6 alkoxy-C2-6 alkynyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, heteroalkoxy, C3- cycloalkyl 7, C3-7 cycloalkyl-C1-6 alkyl, halogen, cyano, nitro, amino, amino substituted by mono- or di- C1-6 alkyl, carboxy, formyl, acyl, C1-6 alkoxycarbonyl, carbamoyl, mono substituted aminocarbonyl - or di-C1-6 alkyl,C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl and -NHCO-C 1-6 alkyl; the term "optionally substituted phenyl" means a phenyl optionally substituted by one to three substituents independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxy-alkenyl C2-6, C2-6 hydroxyalkynyl, C1-6 alkoxy-C2-6 alkenyl, C1-6 alkoxy-C2-6 alkynyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, heteroalkoxy, C3-7 cycloalkyl, C3 cycloalkyl -7-C1-6 alkyl, halogen, cyano, nitro, amino, amino substituted by mono- or di- C1-6 alkyl, carboxyl, formyl, acyl, C1-6 alkoxycarbonyl,carbamoyl, aminocarbonyl substituted by mono- or di- C 1-6 alkyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl and -NHCO-C 1-6 alkyl; the term "optionally substituted heterocyclyl" means a heterocyclyl optionally substituted by one to three substituents independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, hydroxy-alkenyl C2-6, C2-6 hydroxyalkynyl, C1-6 alkoxy-C2-6 alkenyl, C1-6 alkoxy-C2-6 alkynyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, heteroalkoxy, C3-7 cycloalkyl, C3 cycloalkyl -7-C1-6 alkyl, haloqeno, cyano, nitro, amino,amino substituted by mono- or di- C1-6 alkyl, carboxyl, formyl, acyl, C1-6 alkoxycarbonyl, carbamoyl, aminocarbonyl substituted by mono- or di- C1-6 alkyl, C1-6 alkylthio, C1-6 alkylsulfinyl, alkylsulfonyl C1-6 and -NRCO-C1-6 alkyl; the term "optionally substituted heteroaryl" means a heteroaryl optionally substituted by one to three substituents independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C2- hydroxyalkenyl 6, C2-6 hydroxyalkynyl, C1-6 alkoxy-C2-6 alkenyl, C1-6 alkoxy-C2-6 alkynyl, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, heteroalkoxy,C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkyl, halogen, cyano, nitro, amino, amino substituted by mono- or di- C1-6 alkyl, carboxyl, formyl, acyl, C1-6 alkoxycarbonyl, carbamoyl, aminocarbonyl substituted by mono- or di- C1-6 alkyl, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl and -NHCO-C1-6 alkyl; the term "heteroalkyl" means a C1-6 alkyl substituted by one or more substituents independently selected from the group consisting of nitro, hydroxy, cyano, C1-6 alkoxy, formyl, acyl, carboxyl, C1-6 alkylthio, C1-6 alkylsulfinyl , C1-6 alkylsulfonyl, carbamoyl, amino and amino substituted by mono- or di- C1-6 alkyl;the term "heteroalkoxy" means a C1-6 alkoxy substituted by one or more substituents independently selected from the group consisting of nitro, hydroxy, cyano, C1-6 alkoxy, formyl, acyl, carboxyl, C1-6 alkylthio, C1-6 alkylsulfinyl , C1-6 alkylsulfonyl, carbamoyl, amino and amino substituted by mono- or di- C1-6 alkyl; the term ôaciloö means an R-C (O) -,R is C1-6, C1-6, C1-6 halide, c3-7 or c3-7-tar C1-6. Item 21: composition of pharmacology, including a compound, according to any one of requirements 1-19 and a pharmaceutically acceptable precursor chemical.