Patent ID: 6716841
Filing Date: 2004-04-06
Classification: A61P,C07D

Abstract:
A compound of formula B: or a stereoisomer or pharmaceutically acceptable salt thereof;G is a group of formula I or II: ring D is selected from â€”(CH2)3â€”, â€”(CH2)4â€”, â€”CH2N&boxH;CHâ€”, â€”CH2CH2N&boxH;CHâ€”, and a 5-6 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S; ring D, when present, is substituted with 0-2 R, provided that when ring D is unsubstituted, it contains at least one heteroatom; E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, substituted with 0-1 R; R is selected from Cl, F, Br, I, OH, C1-3 alkoxy, NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), and CH2CH2N(C1-3 alkyl)2; alternatively, ring D is absent; when ring D is absent, ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and ring E is substituted with Ra and Rb; Ra is selected from H, F, Cl, Br, I, SR3, CO2R3, NO2, (CH2)tOR3, C1-4 alkyl, OCF3, CF3, C(O)NR7R8, and (CR8R9)tNR7R8; Rb is selected from F, Cl, Br, I, OH, C1-3 alkoxy, CN, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), C(O)NR7R8, (CR8R9)tNR7R8, SH, C1-3 alkyl-S, S(O)R3b, S(O)2R3a, S(O)2NR2R2a, OCF3, and a 5-6 membered heteroaromatic system containing from 1-4 heteroatoms selected from the group N, O, and S and substituted with Rc; alternatively, Ra and Rb combine to form methylenedioxy or ethylenedioxy; Rc is selected from OH, SH, C1-3 alkoxy, C1-3 thioalkoxy, NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), and CH2CH2N(C1-3 alkyl)2; Z is N or CR1a; R1a is absent or selected from â€”(CH2)râ€”R1c, â€”CH&boxH;CHâ€”R1c, NCH2R1d, OCH2R1d, SCH2R1d, NH(CH2)2(CH2)tR1c, O(CH2)2(CH2)tR1c, and S(CH2)2(CH2)tR1c; R1b is absent or selected from â€”(CH2)râ€”R1c, â€”CH&boxH;CHâ€”R1c, NCH2R1d, OCH2R1d, SCH2R1d, NH(CH2)2(CH2)tR1c, O(CH2)2(CH2)tR1c, and S(CH2)2(CH2)tR1c; alternatively, R1a and R1b, when both are present, together with the atoms to which they are attached form a 5-8 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4 and which contains from 0-2 heteroatoms selected from the group consisting of N, O, and S; R1c is selected from H, C1-3 alkyl, F, Cl, Br, I, â€”CN, â€”CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2c, S(O)pR2b, NR2(CH2)rOR2, CH(&boxH;NR2c)NR2R2a, NR2C(O)R2b, NR2C(O)NHR2b, NR2C(O)2R2a, OC(O)NR2aR2b, C(O)NR2R2a, C(O)NR2(CH2)rOR2, SO2NR2R2a, NR2SO2R2b, C3-6 carbocyclic residue substituted with 0-2 R4, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4; R1d is selected from H, CH(CH2OR2)2, C(O)R2c, 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 residue substituted with 0-2 R4b, a C3-6 carbocyclic-CH2â€” residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 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 residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 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 residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 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 residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; alternatively, R2 and R2a, together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4b and containing from 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; R3b, at each occurrence, is selected from H, C1-4 alkyl, and phenyl; R3c, at each occurrence, is selected from C1-4 alkyl, and phenyl; A1 is 2-5 membered linker substituted with 0-2 R4 and selected from C2-4 alkylene, C2-4 alkenylene, (CH2)uO(CH2)u, (CH2)uNH(CH2)u, (CH2)uC(O)(CH2)u, (CH2)uC(O)O(CH2)u, (CH2)uOC(O)(CH2)u, (CH2)uC(O)NH(CH2)u, (CH2)uNHC(O)(CH2)u, (CH2)uS(O)p(CH2)u, (CH2)uSO2NH(CH2)u, and (CH2)uNHSO2(CH2)u, provided that A1 forms other than a Nâ€”O or Nâ€”S bond; alternatively, the CH2â€”A1 group is replaced by a group selected from C&boxH;CHâ€”NH, C&boxH;CHâ€”O, and C&boxH;CHâ€”S; B is selected from: Xâ€”Y, NR2R2a, C(&boxH;NR2)NR2R2a, NR2C(&boxH;NR2)NR2R2a, C3-10 carbocyclic residue substituted with 0-2 R4a, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4a; X is selected from C1-4 alkylene, â€”CR2(CR2R2b)(CH2)tâ€”, â€”C(O)â€”, â€”C(&boxH;NR1d)â€”, â€”CR2(NR1dR2)â€”, â€”CR2(OR2)â€”, â€”CR2(SR2)â€”, â€”C(O)CR2R2aâ€”, â€”CR2R2aC(O), â€”S(O)pâ€”, â€”S(O)pCR2R2aâ€”, â€”CR2R2aS(O)pâ€”, â€”S(O)2NR2â€”, â€”NR2S(O)2â€”, â€”NR2S(O)2CR2R2aâ€”, â€”CR2R2aS(O)2NR2â€”, â€”NR2S(O)2NR2â€”, â€”C(O)NR2â€”, â€”NR2C(O)â€”, â€”C(O)NR2CR2R2aâ€”, â€”NR2C(O)CR2R2aâ€”, â€”CR2R2aC(O)NR2â€”, â€”CR2R2aNR2C(O)â€”, â€”NR2C(O)Oâ€”, â€”OC(O)NR2â€”, â€”NR2C(O)NR2â€”, â€”NR2, â€”NR2CR2R2aâ€”, â€”CR2R2aNR2â€”, O, â€”CR2R2aOâ€”, and â€”OCR2R2aâ€”; Y is selected from: (CH2)rNR2R2a, provided that Xâ€”Y do not form a Nâ€”N, Oâ€”N, or Sâ€”N bond, C3-10 carbocyclic residue substituted with 0-2 R4a, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4a; R4, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, F, Cl, Br, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, NR2C(O)NR2R2a, CH(&boxH;NR2)NR2R2a, CH(&boxH;NS(O)2R5)NR2R2a, NHC(&boxH;NR2)NR2R2a, C(O)NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, NCH2R1d, OCH2R1d, SCH2R1d, N(CH2)2(CH2)tR1c, O(CH2)2(CH2)tR1c, and S(CH2)2(CH2)tR1c; R4a, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, (CH2)râ€”F, (CH2)râ€”Br, (CH2)râ€”Cl, Cl, Br, F, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, CH(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, C(O)NHSO2â€”C1-4 alkyl, NR2SO2R5, S(O)pR5, and (CF2)rCF3; alternatively, one R4a is a 5-6 membered aromatic heterocycle containing from 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 H, &boxH;O, (CH2)rOR3, F, Cl, Br, I, C1-4 alkyl, â€”CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CH(&boxH;NR3)NR3R3a, NR3C(&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, CH(&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 contains from 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; r, at each occurrence, is selected from 0, 1, 2, and 3; s, at each occurrence, is selected from 0, 1, and 2; t, at each occurrence, is selected from 0, 1, 2, and 3; and, u, at each occurrence, is selected from 0, 1, 2, and 3.