Patent ID: 6630468
Filing Date: 2003-10-07
Classification: A61P,C07D

Abstract:
A compound of formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;M1 is CR1c; M2 is NR1a; D is selected from C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), C(O)NR7R8, and CR8R9NR7R8; E is selected from phenyl substituted with 1 R; R is selected from H, Cl, F, Br, I, (CH2)tOR3, C1-4 alkyl, OCF3, CF3, C(O)NR7R8, and (CR8R9)tNR7R8; G is absent; Z is C(O)CH2 or C(O)NH provided that Z does not form a Nâ€”N bond with group A; R1a and R1b are, at each occurrence, independently selected from H, â€”(CH2)râ€”R1â€², NHCH2R1â€³, OCH2R1â€³, SCH2R1â€³, NH(CH2)2(CH2)tR1â€², O(CH2)2(CH2)tR1â€², and S(CH2)2(CH2)tR1â€³; R1c is selected from H, â€”(CH2)qâ€”R1â€², C1-3 alkyl, C(O)R2c, (CF2)rCO2R2c, C(O)NR2R2a, C3-6 carbocyclic groups substituted with 0-2 R4, and 5-10 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4; R1â€² is selected from H, C1-3 alkyl, halo, (CF2)rCF3, OR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2c, S(O)pR2b, NR2(CH2)rOR2, NR2C(O)R2b, NR2C(O)NHR2b, NR2C(O)2R2a, OC(O)NR2b, C(O)NR2R2a, SO2NR2R2a, NR2SO2R2b, C3-6 carbocyclic groups substituted with 0-2 R4, and 5-10 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4; R1â€³ is selected from H, C(O)R2b, C(O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a; R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C3-6 carbocyclic groups substituted with 0-2 R4b, and 5-6 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2a, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C3-6 carbocyclic groups substituted with 0-2 R4b, and 5-6 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic groups substituted with 0-2 R4b, and 5-6 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R2c, at each occurrence, is selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic groups substituted with 0-2 R4b, and 5-6 membered heterocyclic system consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; alternatively, R2 and R2a combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4b which comprises 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R3, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; R3a, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; A is selected from: C3-10 carbocyclic groups substituted with 0-2 R4; B is selected from: Xâ€”Y, C3-10 carbocyclic groups substituted with 0-2 R4a, pyrrolidinyl substituted with 0-2 R4a and imidazolyl substituted with 0-2 R4a; X is selected from C1-4 alkylene, and â€”C(O)â€”; Y is S pyrrolidinyl substituted with 0-2 R4a; R4, at each occurrence, is selected from &boxH;O, (CH2)rOR2, halo, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, C(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, NCH2R1â€³, OCH2R1â€³, SCH2R1â€³, N(CH2)2(CH2)tR1â€², O(CH2)2(CH2)tR1â€², and S(CH2)2(CH2)tR1â€², alternatively, one R4 is a 5-6 membered aromatic heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S; R4a, at each occurrence, is selected from &boxH;O, (CH2)rOR2, halo, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2b, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, C(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, and (CF2)rCF3; alternatively, one R4a is a 5-6 membered aromatic heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-1 R5; R4b, at each occurrence, is selected from &boxH;O, (CH2)rOR3, halo, C1-4 alkyl, â€”CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, C(&boxH;NR3)NR3R3a, NHC(&boxH;NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2â€”C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)pâ€”C1-4 alkyl, S(O)p-phenyl, and (CF2)rCF3; R5, at each occurrence, is selected from CF3, C1-6 alkyl, phenyl substituted with 0-2 R6, and benzyl substituted with 0-2 R6; R6, at each occurrence, is selected from H, OH, (CH2)rOR2, halo, C1-4 alkyl, CN, NO2, (CH2)rNR2R2a,(CH2)rC(O)R2b, NR2C(O)R2b, NR2C(O)NR2R2a, C(&boxH;NH)NH2, NHC(&boxH;NH)NH2, SO2NR2R2a, NR2SO2NR2R2a, and NR2SO2C1-4 alkyl; R7, at each occurrence, is selected from H, OH, C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 alkoxy, C1-4 alkoxycarbonyl, (CH2)n-phenyl, C6-10 aryloxy, C6-10 aryloxycarbonyl, C6-10 arylmethylcarbonyl, C1-4 alkylcarbonyloxy C1-4 alkoxycarbonyl, C6-10 arylcarbonyloxy C1-4 alkoxycarbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C1-4 alkoxycarbonyl; R8, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl; alternatively, R7 and R8 combine to form a 5 or 6 membered saturated, ring which comprises 0-1 additional heteroatoms selected from the group consisting of N, O, and S; R9, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl; n, at each occurrence, is selected from 0, 1, 2, and 3; p, at each occurrence, is selected from 0, 1, and 2; q, at each occurrence is selected from 1 and 2; r, at each occurrence, is selected from 0, 1, 2, and 3; s, at each occurrence, is 0, and t, at each occurrence, is selected from 0 and 1.