Patent ID: 6710058
Filing Date: 2004-03-23
Classification: A61P,C07D

Abstract:
A compound of Formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;the piperidinone ring of formula I is substituted with 0-2 R1a; G is a group of formula IIa or IIb: G1 is S(O)NR3; ring D, including the two atoms of Ring E to which it is attached, is phenyl substituted with 0-2 R; E is phenyl substituted with 0-2 R; R is selected from 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), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(&boxH;NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3alkyl)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)pR3f, (CR8R9)tS(O)R3c, (CR8R9)tS(O)2R3c, and OCF3; alternatively, the bridging portion of ring D is absent, and ring E is phenyl substituted with Ra and Rb; Ra and Rb, at each occurrence, are independently 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),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 alky)2, (CR8R9)tC(O)H, (CR8R9)tC(O)R2c, (CR8R9)tNR7R8, (CR8R9)tC(O)NR7R8, (CR8R9)tOR3a, (CR8R9)tNR7C(O)R3f, (CR8R9)tS(O)pNR7R8, (CR8R9)tNR7S (O)pR3f, (CR8R9)tS(O)R3c, (CR8R9)tS(O)2R3c, and OCF3; A is phenyl substituted with 0-2 R4; provided that B and ring M are attached to different atoms on A; B is selected from: Y and Xâ€”Y; X is selected from â€”(CR2R2a)1-4â€”, â€”CR2(CR2R2b)(CH2)tâ€”, â€”C(O)â€”, â€”C(&boxH;NR1c)â€”, â€”CR2(NR1cR2)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€”OCR2R2a; Y is selected from: â€”(CH2)rNR2R2a, provided that Xâ€”Y do not form a Nâ€”N, Oâ€”N, or Sâ€”N bond, C3-10 carbocycle 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; provided that B and Y are other than tetrazolyl; R1a, is selected from H, â€”(CH2)rR1b, â€”CH&boxH;CHâ€”R1b, NCH2R1c, OCH2R1c, S(O)pCH2R1c, NH(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, and S(CH2)2(CH2)tR1b, provided that R1a forms other than an N-halo, Nâ€”N, Nâ€”S, Nâ€”O, or Nâ€”CN bond with the group to which it is attached; R1b is selected from H, C1-3 alkyl, F, Cl, Br, I, CN, CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, C(O)OR2, 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€”S, 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; R2, at each occurrence, is selected from H, CF3, C1-6 alkyl substituted with 0-2 R4b, benzyl, a C3-10 carbocycle â€”(CH2)râ€” substituted with 0-2 R4b, and (5-6 membered heterocyclic system)â€”(CH2)râ€” 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 substituted with 0-2 R4b, benzyl, a C3-10 carbocycle â€”(CH2)râ€” residue substituted with 0-2 R4b, and (5-6 membered heterocyclic system)â€”(CH2)râ€” 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; R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-10 carbocycle â€”(CH2)râ€” substituted with 0-2 R4b, and (5-6 membered heterocyclic system)â€”(CH2)râ€” 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, C3-10 carbocycle â€”(CH2)râ€” substituted with 0-2 R4b, and (5-6 membered heterocyclic system)â€”(CH2)râ€” containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b; R3, 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; cycloalkyl(C0-4 alkyl)-substituted with 0-3 R1a; heterocyclyl(C0-4 alkyl)-substituted with 0-3 R1a; aryl(C0-4 alkyl)-substituted with 0-3 R1a; heteroaryl(C0-4 alkyl)-substituted with 0-3 R1a; R3a and R3b, at each occurrence, are independently selected from H, C1-4 alkyl, phenyl, and benzyl; R3c, at each occurrence, is selected from C1-4 alkyl, phenyl, and benzyl; R3d, at each occurrence, is selected from H and C1-4 alkyl; R3e, 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; cycloalkyl(C0-4 alkyl)-substituted with 0-3 R1a; heterocyclyl(C0-4 alkyl)-substituted with 0-3 R1a; aryl(C0-4 alkyl)-substituted with 0-3 R1a; heteroaryl(C0-4 alkyl)-substituted with 0-3 R1a; R3f, at each occurrence, is selected from: C1-6 alkyl substituted with 0-2 R1a; C2-6 alkenyl substituted with 0-2 R1a; C2-6 alkynyl substituted with 0-2 R1a; cycloalkyl(C0-4 alkyl)-substituted with 0-3 R1a; heterocyclyl(C0-4 alkyl)-substituted with 0-3 R1a; aryl(C0-4 alkyl)-substituted with 0-3 R1a; heteroaryl(C0-4 alkyl)-substituted with 0-3 R1a; 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)2R3f)NR2R2a, NHC(&boxH;NR2)NR2R2a, C(O)NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, NR2SO2R3f, S(O)pR3f, (CF2)rCF3, NCH2R1c, OCH2R1c, SCH2R1c, N(CH2)2(CH2)tR1b, O(CH2)2(CH2)tR1b, S(CH2)2(CH2)tR1b, and 5-6 membered carbocycle substituted with 0-1 R5, and a 5-6 membered 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 R5; R4a, at each occurrence, is selected from H, &boxH;O, (CH2)rOR2, (CH2)rF, (CH2)râ€”Br, (CH2)rCl, C1-4 alkyl, â€”CN, NO2, (CH2)rNR2R2a, (CH2)rC(O)R2c, NR2C(O)R2b, C(O)NR2R2a, (CH2)rN&boxH;CHOR3, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, C(&boxH;NR2)NR2R2a, NHC(&boxH;NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2â€”C1-4 alkyl, C(O)NHSO2â€”C1-4 alkyl, NR2SO2R3f, S(O)pR3f, (CF2)rCF3, and 5-6 membered carbocycle substituted with 0-1 R5, and a 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p substituted with 0-R5; provided that when R4a is substituted with R3, R3 is unsubstituted; R4b, at each occurrence, is selected from H, &boxH;O, (CH2)rOR3, (CH2)râ€”F, (CH2)rCl, (CH2)rBr, (CH2)râ€”I, C1-4 alkyl, (CH2)rCN, (CH2)rNO2, (CH2)rNR3R3a, (CH2)rC(O)R3, (CH2)rC(O)OR3c, (CH2)rNR3C(O)R3a, (CH2)râ€”C(O)NR3R3a, (CH2)rNR3C(O)NR3R3a, (CH2)râ€”C(&boxH;NR3)NR3R3a, (CH2)rNR3C(&boxH;NR3)NR3R3a, (CH2)râ€”SO2NR3R3a, (CH2)rNR3SO2NR3R3a, (CH2)râ€”NR3SO2â€”C1-4 alkyl, (CH2)râ€”NR3SO2CF3, (CH2)rNR3SO2-phenyl, (CH2)râ€”S(O)pCF3, (CH2)râ€”S(O)pâ€”C1-4 alkyl, (CH2)râ€”S(O)p-phenyl, and (CF2)rCF3; provided that when R4a is substituted with R3, R3 is unsubstituted; R5, at each occurrence, is selected from H, C1-6 alkyl, &boxH;O, (CH2)rOR3, F, Cl, Br, I, 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, NR3SO2-phenyl, S(O)pCF3, S(O)pâ€”C1-4 alkyl, S(O)p-pheny, (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 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 5-10 membered saturated, partially saturated or unsaturated ring which contains 0-2 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; and t, at each occurrence, is selected from 0, 1, 2, and 3.