Patent ID: 6790845
Filing Date: 2004-09-14
Classification: A61P,C07D

Abstract:
A compound of Formula (I): or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:ring D is absent; ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, thienyl and trizaolyl, and ring E is substituted with 0-2 Ra; Ra is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(&boxH;NR7), C(O)NR7R8, (CR8R9)tNR7R8, SH, SCH3, SCH2CH3, SCH(CH3)2, SCH2CH2CH3, S(O)R3b, S(O)2R3a, S(O)2NR2R2a, and OCF3; alternatively, two Ras combine to form methylenedioxy or ethylenedioxy; alternatively, ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, and thienyl, and ring E is substituted with 1 R and with a 5-6 membered aromatic heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-1 carbonyl groups and 0-2 R1; ring F completes a 5-7 membered heterocycle consisting of carbon atoms, 1-3 heteroatoms selected from the group consisting of N, NH, O, and â€”S(O)pâ€”, 0-2 additional double bonds, and 0-2 carbonyl groups, provided that other than a Oâ€”O, Oâ€”S, or Sâ€”S bond is present in the ring and ring F is substituted with 0-1 R4c; ring G is substituted with 0-2 R1a and is selected from: Z is selected from H, S(O)2NHR3, C(O)R3, C(O)NHR3, C(O)OR3f, S(O)R3f, S(O)2R3f, C1-6 alkyl substituted with 0-2 R1a; C2-6 alkenyl substituted with 0-2 R1a; C2-6 alkynyl substituted with 0-2 R1a; â€”(C0-4 alkyl)-C3-10-carbocycle substituted with 0-3 R1a; and â€”(C0-4 alkyl)-5-12 membered-heterocycle substituted with 0-3 R1a; A is selected from: C3-10 carbocycle substituted with 0-2 R4, and 5-12 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-2 R4; B is selected from: Y, Xâ€”Y, (CH2)0-2C(O)NR2R2a, (CH2)0-2NR2R2a, C(&boxH;NR2)NR2R2a, and NR2C(&boxH;NR2)NR2R2a, provided that G3 and B are attached to different atoms on A; X is selected from â€”(CR2R2a)1-4â€”, â€”CR2(CR2R2b)(CH2)tâ€”, â€”C(O)â€”, â€”C(&boxH;NR1c)â€”, â€”CR2(NR2R2a)â€”, â€”CR2(OR2)â€”, â€”CR2(SR2)â€”, â€”C(O)CR2R2aâ€”, â€”CR2R2aC(O), â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, â€”SCR2R2aâ€”, â€”S(O)CR2R2aâ€”, â€”S(O)2CR2R2aâ€”, â€”CR2R2aSâ€”, â€”CR2R2aS(O)â€”, â€”CR2R2aS(O)2â€”, 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€”NR2â€”, â€”NR2CR2R2aâ€”, â€”CR2R2aNR2â€”, O, â€”CR2R2aOâ€”, and â€”OCR2R2aâ€”; Y is selected from: â€”(CH2)rNR2R2a; C3-10 carbocycle substituted with 0-2 R4a; and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-2 R4a; provided that Xâ€”Y do not form a Nâ€”N, Oâ€”N, or Sâ€”N bond; V is selected from C, CH, and N; W is a bond; R1 is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C(&boxH;NR8)NR7R9, NHC(&boxH;NR8)NR7R9, NR8CH(=NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, (CR8R9)tC(O)H, (CR8R9)tC(O)R2c, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, (CR8R9)tOR3a, (CR8R9)tNR7C(O)R7, (CR8R9)tS(O)pNR7R8, (CR8R9)tNR7S(O)pR7, (CR8R9)tSR3, (CR8R9)tS(O)R3c, (CR8R9)tS(O)2R3c, and OCF3; R1a is selected from H, â€”(CH2)râ€”R1b, â€”CH&boxH;CHâ€”R1b, NCH2R1c, NR2R2a, OCH2R1c, SCH2R1c, NH(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, S(CH2)2(CH2)tR1b, S(O)p(CH2)rR1d, O(CH2)rR1d, NR3(CH2)rR1d, OC(O)NR3(CH2)rR1d, NR3C(O)NR3(CH2)rR1d, NR3C(O)O(CH2)rR1d, and NR3C(O)(CH2)rR1d, provided that R1a forms other than an N-halo, Nâ€”N, Nâ€”S, Nâ€”O, or Nâ€”CN bond; alternatively, when two R1as are attached to adjacent atoms, together with the atoms to which they are attached they form a 5-7 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O)p, 0-1 Z, and 0-3 ring double bonds; this ring being substituted with 0-2 R4b; R1b is selected from H, C1-3 alkyl, F, Cl, Br, I, â€”ON, â€”CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)rCO2R2a, S(O)pR2b, NR2(CH2)rOR2, C(&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, C3-10 carbocycle substituted with 0-2 R4a, and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, substituted with 0-2 R4a, provided that R1b forms other than an N-halo, Nâ€”N, Nâ€”S, Nâ€”O, or Nâ€”CN bond with the group to which it is attached; R1c is selected from H, CH(CH2OR2)2, C(O)R2c, C(O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a; R1d is selected from C3-6 carbocycle substituted with 0-2 R4a, and 5-10 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and substituted with 0-2 R4a, provided that R1d forms other than an N-N, N-S, or N-O bond; R2 and R2a, at each occurrence, are independently selected from H, CF3, C1-6 alkyl, benzyl; â€”(CH2)râ€”C3-10 carbocycle substituted with 0-2 R4b; and â€”(CH2)r-5-6 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and 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 consisting of: 0-1 additional heteroatoms selected from the group consisting of N, O, and S(O)p; R2b and R2c, at each occurrence, are independent selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl; â€”(CH2)râ€”C3-10 carbocycle substituted with 0-2 R4b; and â€”(CH2)r-5-6 membered heterocycle consisting of carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and substituted with 0-2 R4b; R3 and R3a, at each occurrence, is independently selected from H, C1-4 alkyl, benzyl and phenyl; R3b, at each occurrence, is selected from H, C1-6 alkyl substituted with 0-2 R1a, C2-6 alkenyl substituted with 0-2 R1a, C2-6 alkynyl substituted with 0-2 R1a, â€”(C0-4 alkyl)-cycloalkyl substituted with 0-3 R1a, â€”(C0-4 alkyl)-heterocycle substituted with 0-3 R1a, â€”(C0-4 alkyl)-aryl substituted with 0-3 R1a, and â€”(C0-4 alkyl)-heteroaryl substituted with 0-3 R1a; R3c, at each occurrence, is selected from C1-4 alkyl, benzyl, and phenyl; R3d, at each occurrence, is selected from H, C1-4 alkyl, C1-4 alkyl-phenyl, and C(&boxH;O)R3c; 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, C(&boxH;NR2)NR2R2a, C(&boxH;NS(O)2R5)NR2R2a, NHC(&boxH;NR2)NR2R2a, C(O)NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)rCF3, NCH2R1c, OCH2R1c, SCH2R1c, N(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, and S(CH2)2(CH2)tR1b; alternatively, one R4 is a (CR3R3a)-5-6 membered aromatic heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p; R4a, at each occurrence, is selected from H, &boxH;O, (CR3R3a)rOR2, (CR3R3a)rF, (CR3R3a)rBr, (CR3R3a)rCl, C1-4 alkyl, (CR3R3a)rCN, (CR3R3a)rNO2, (CR3R3a)rNR2R2a, (CR3R3a)rC(O)R2c, (CR3R3a)rNR2C(O)R2b, (CR3R3a)rC(O)NR2R2a, (CR3R3a)rN&boxH;CHOR3, (CR3R3a)rC(O)NH(CH2)2NR2R2a, (CR3R3a)rNR2C(O)NR2R2a, (CR3R3a)rC(=NR2)NR2R2a, (CR3R3a)rNHC(&boxH;NR2)NR2R2a, (CR3R3a)rSO2NR2R2a, (CR3R3a)rNR2SO2NR2R2a, (CR3R3a)rNR2SO2â€”C1-4 alkyl, (CR3R3a)rC(O)NHSO2â€”C1-4 alkyl, (CR3R3a)NR2SO2R5, (CR3R3a)rS(O)pR5, (CR3R3a)r(CF2)rCF3, (CR3R3a)r-5-6 membered carbocycle substituted with 0-1 R5, and a (CR3R3a)r-5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, and substituted with 0-1 R5; R4b, at each occurrence, is selected from H, &boxH;O, (CH2)rOR3, (CH2)rF, (CH2)rCl, (CH2)rBr, (CH2)rI, C1-4 alkyl, (CH2)rCN, (CH2)rNO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, (CH2)rNR3C(O)R3a, (CH2)rC(O)NR3R3a, (CH2)rNR3C(O)NR3R3a, (CH2)râ€”C(&boxH;NR3)NR3R3a, (CH2)rNR3C(&boxH;NR3)NR3R3a, (CH2)rSO2NR3R3a, (CH2)rNR3SO2NR3R3a, (CH2)rNR3SO2â€”C1-4 alkyl, (CH2)rNR3SO2CF3, (CH2)rNR3SO2-phenyl, (CH2)rS(O)pCF3, (CH2)rS(O)pâ€”C1-4 alkyl, (CH2)rS(O)p-phenyl, and (CH2)r(CF2)rCF3; R4c is selected from H, C1-4 alkyl, â€”(CH2)uOR3b, â€”(CH2)uNR3bR3b, â€”CH2)uC(O)R3b, â€”(CH2)uCO2R3b, â€”(CH2)uC(O)NR3bR3b, â€”(CH2)uSO2NR3bR3b, â€”(CH2)uNHSO2R3b, and (CR3R3a)r-5-6 membered carbocycle substituted with 0-1 R5; R5, at each occurrence, is selected from H, C1-6 alkyl, &boxH;O, (CH2)rOR3, F, Cl, Br, I, â€”CN, NO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CH(&boxH;NOR3d), C(&boxH;NR3)NR3R3a, NR3C(&boxH;NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2â€”C1-4 alkyl, NR3SO2CF3, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)pâ€”C1-4 alkyl, S(O)p-phenyl, (CF2)rCF3, phenyl substituted with 0-2 R6, naphthyl 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 alkylaininocarbonyl, phenylaminocarbonyl, and phenyl C1-4 alkoxycarbonyl; R8, at each occurrence, is selected from H, C1-6 alkyl, and â€”(CH2)n-phenyl; alternatively, R7 and R8, when attached to the same nitrogen, combine to form a 5 or 6 membered saturated ring consisting of carbon atoms and 0-2 additional heteroatoms selected from the group consisting of N, O, and S(O)p; R9, at each occurrence, is selected from H, C1-6 alkyl, and â€”(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; t, at each occurrence, is selected from 0, 1, 2, and 3; and, u, at each occurrence, is selected from 1, 2, and 3.