Patent ID: 6586446
Filing Date: 2003-07-01
Classification: A61P,C07D

Abstract:
A compound of formula (I):Aâ€”Eâ€”NR1â€”Gâ€ƒâ€ƒ(I) or stereoisomers or pharmaceutically acceptable salts thereof, wherein:A is selected from E is selected from â€”(CR7R8)â€”(CR9R10)vâ€”(CR11R12), â€ƒring D is selected from a C3-6 carbocyclic residue and a 5 or 6 membered heterocycle; G is selected from â€”C(O)R3, â€”C(O)NR2R3, â€”C(O)OR3, â€”SO2NR2R3, â€”SO2R3, â€”C(&boxH;S)NR2R3, C(&boxH;NR1a)NR2R3, C(&boxH;CHCN)NR2R3, C(&boxH;CHNO2)NR2R3, C(&boxH;C(CN)2)NR2R3, W, at each occurrence, is independently selected from C or N, provided at least two of W are C; X1 and X2 are independently selected from C and N; Z1 is selected from C and N; Z2 is selected from NR1â€², O, S and C; R1, R1â€² and R2 are independently selected from H, C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, (CH2)rC3-6 cycloalkyl, and a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 Ra; R1a is independently selected from H, C1-6 alkyl, â€”OH, â€”CN, â€”NO2, (CH2)rC3-6 cycloalkyl, and a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 Ra; Ra, at each occurrence, is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CHRâ€²)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CHRâ€²)rNRbRb, (CHRâ€²)rOH, (CHRâ€²)rORc, (CHRâ€²)rSH, (CHRâ€²)rSRc, (CHRâ€²)rC(O)Rb, (CHRâ€²)rC(O)NRbRb, (CHRâ€²)rNRbC(O)Rb, (CHRâ€²)rC(O)ORb, (CHRâ€²)rOC(O)Rc, (CHRâ€²)rCH(&boxH;NRb)NRbRb, (CHRâ€²)rNHC(&boxH;NRb)NRbRb, (CHRâ€²)rS(O)pRc, (CHRâ€²)rS(O)2NRbRb, (CHRâ€²)rNRbS(O)2Rc, and (CHRâ€²)rphenyl; Rb, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; Rc, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, and phenyl; alternatively, R1 and R2 join to form a 5, 6, or 7-membered ring substituted with 0-3 Ra; R3 is selected from a (CR3â€²R3â€³)râ€”C3-10 carbocyclic residue substituted with 0-5 R15 and a (CR3â€²R3â€³)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R15; R3â€² and R3â€³, at each occurrence, are selected from H, C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and phenyl; R4 is absent, taken with the nitrogen to which it is attached to form an N-oxide, or selected from C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, (CH2)rC3-6 cycloalkyl, (CH2)qC(O)R4b, (CH2)qC(O)NR4aR4aâ€², (CH2)qC(O)OR4a, and a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R4c; R4a and R4aâ€², at each occurrence, are selected from H, C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and phenyl; R4b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, (CH2)rC3-6 cycloalkyl, C2-8 alkynyl, and phenyl; R4c, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CH2)rOH, (CH2)rSC1-5 alkyl, (CH2)rNR4aR4aâ€², and (CH2)rphenyl; R7, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkyzyl, (CHRâ€²)qOH, (CHRâ€²)qSH, (CHRâ€²)qOR7d, (CHRâ€²)qSR7d, (CHRâ€²)qNR7aR7aâ€², (CHRâ€²)rC(O)OH, (CHRâ€²)rC(O)R7b, (CHRâ€²)rC(O)NR7aR7aâ€², (CHRâ€²)qNR7aC(O)R7b, (CHRâ€²)qNR7aC(O)H, (CHRâ€²)rC(O)OR7a, (CHRâ€²)qOC(O)R7b, (CHRâ€²)qS(O)pR7b, (CHRâ€²)qS(O)2NR7aR7aâ€², (CHRâ€²)qNR7aS(O)2R7b, (CHRâ€²)qNHC(O)NR7aR7aâ€², (CHRâ€²)qNHC(O)OR7a, (CHRâ€²)qOC(O)NR7aR7aâ€², C1-6 haloalkyl, a (CHRâ€²)râ€”C3-10 carbocyclic residue substituted with 0-3 R7c, and a (CHRâ€²)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R7c; R7a and R7aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R7e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R7e; R7b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, c2-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-2 R7e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R7e; R7c, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR7fR7f, (CH2)rOH, (CH2)rOC1-4 alkyl, (CH2)rSC1-4 alkyl, (CH2)rC(O)OH, (CH2)rC(O)R7b, (CH2)rC(O)NR7fR7f, (CH2)rNR7fC(O)R7b, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R7b, (CH2)rC(&boxH;NR7f)NR7fR7f, (CH2)rS(O)ppR7b, (CH2)rNHC(&boxH;NR7f)NR7fR7f, (CH2)rS(O)2NR7fR7f, (CH2)rNR7fS(O)2R7b, and (CH2)rphenyl substituted with 0-3 R7e; R7d, at each occurrence, is selected from methyl, CF3, C2-6 alkyl substituted with 0-3 R7e, C3-6 alkenyl, C3-6 alkynyl, and a C3-10 carbocyclic residue substituted with 0-3 R7c; R7e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CHH2)rSC1-5 alkyl, (CH2)rNR7fR7f, and (CH2)rphenyl; R7f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R8 is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R8a; R8a, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR7fR7f, and (CH2)rphenyl; alternatively, R7 and R8 join to form C3-7 cycloalkyl, &boxH;NR8b, or &boxH;O; R8b is selected from H, C1-6 alkyl, C3-6 cycloalkyl, OH, CN, and (CH2)r-phenyl; R9, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CHRâ€²)rOH, (CHRâ€²)rSH, (CHRâ€²)rOR9d, (CHRâ€²)rSR9d, (CHRâ€²)rNR9aR9aâ€², (CHRâ€²)rC(O)OH, (CHRâ€²)rC(O)R9b, (CHRâ€²)rC(O)NR9aR9aâ€², (CHRâ€²)rNR9aC(O)R9b, (CHRâ€²)rNR9aC(O)H, (CHRâ€²)rNR9aC(O)NR9aR9a, (CHRâ€²)rC(O)OR9a, (CHRâ€²)rOC(O)R9b, (CHRâ€²)rS(O)pR9b, (CHRâ€²)rS(O)2NR9aR9aâ€², (CHRâ€²)rNR9aS(O)2R9b, C1-6 haloalkyl, a (CHRâ€²)râ€”C3-10 carbocyclic residue substituted with 0-5 R9c, and a (CHRâ€²)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R9c; R9a and R9aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R9e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, sibstituted with 0-3 R9e; R9b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-2 R9e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R9e; R9c, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR9fR9f, (CH2)rOH, (CH2)rOC1-4 alkyl, (CH2)rSC1-4 alkyl, (CH2)rC(O)OH, (CH2)rC(O)R9b, (CH2)rC(O)NR9fR9f, (CH2)rNR9fC(O)R9b, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R9b, (CH2)rC(&boxH;NR9f)NR9fR9f, (CH2)rS(O)pR9b, (CH2)rNHC(&boxH;NR9f)NR9fR9f, (CH2)rS(O)2NR9fR9f, (CH2)rNR9fS(O)2R9b, and (CH2)rphenyl substituted with 0-3 R9e; R9d, at each occurrence, is selected from methyl, CF3, C2-6 alkyl substituted with 0-3 R9e, C3-6 alkenyl, C3-6 alkynyl, a C3-10 carbocyclic residue substituted with 0-3 R9c, and a 5-6 membered hetorocyclic system containing 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R9c; R9e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR9fR9f, and (CH2)rphenyl; R9f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R10, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CH2)rOH, (CH2)rOR10d, (CH2)rSR10d, (CH2)rNR10aR10aâ€², (CH2)rC(O) OH, (CH2)rC(O)R10b, (CH2)rC(O)NR10aR10aâ€², (CH2,)rNR10aC(O)R10a, (CH2)rNR10aC(O)H, (CH2)rC(O)OR10a, (CH2)rOC(O)R10b, (CH2)rS(O)pR10b, (CH2)rS(O)2NR10aR10aâ€², (CH2)rNR10aS(O)2R10b, C1-6 haloalkyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0&nldr;5 R10c, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R10c; R10a and R10aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R10e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R10e; R10b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-2 R10e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R10e; R10c, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR10fR10f, (CH2)rOH, (CH2)rOC1-4 alkyl, (CH2)rSC1-4 alkyl, (CH2)rC(O)OH, (CH2)rC(O)R10b, (CH2)rC(O)NR10fR10f, (CH2)rNR10fC(O)R10a, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R10b, (CH2)rC(&boxH;NR10f)NR10fR10f, (CH2)rS(O)pR10b, (CH2)rNHC(&boxH;NR10f)NR10fR10f, (CH2)rS(O)2NR10fR10f, (CH2)rNR10fS(O)2R10b, and (CH2)rphenyl substituted with 0-3 R10e; R10d, at each occurrence, is selected from methyl, CF3, C2-6 alkyl substituted with 0-3 R10e, C3-6 alkenyl, C3-6 alkynyl, a C3-10 carbocyclic residue substituted with 0-3 R10c, and a 5-6 membered heterocyclic system containing 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-3 R10c; R10e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR10fR10f, and (CH2)rphenyl; R10f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; alternatively, R9 and R10 join to form C3-7 cycloalkyl, 5-6-membered cyclic ketal, or &boxH;O; with the proviso that when R10 is â€”OH, R9 is not halogen, cyano, or bonded to the carbon to which it is attached through a heteroatom; R11, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)qOH, (CH2)qSH, (CH2)qOR11d, (CH2)qSR11d, (CH2)qNR11aR11aâ€², (CH2)rC(O)OH, (CH2)rC(O)R11b, (CH2)rC(O)NR11aR11aâ€², (CH2)qNR11aC(O)R11b, (CH2)qNR11aC(O)NR11aR11a, (CH2)rC(O)OR11a, (CH2)qC(O)R11b, (CH2)qS(O)pR11b, (CH2)qS(O)2NR11aR11aâ€², (CH2)qNR11aS(O)2R11b, C1-6 haloalkyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R11c, and a (CH2)r-5-10 nembered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R11c; R11a and R11aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R11e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R11e; R11b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-2 R11e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R11e; R11c, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR11fR11f, (CH2)rOH, (CH2)rOC1-4 alkyl, (CH2)rSC1-4 alkyl, (CH2)rC(O)OH, (CH2)rC(O)R11b, (CH2)rC(O)NR11fR11f, (CH2)rNR11fC(O)R11a, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R11b, (CH2)rC(&boxH;NR11f)NR11fR11f, (CH)rNHC(&boxH;NR11f)NR11fR11f, (CH2)rS(O)pR11b, (CH2)rS(O)2NR11fR11f, (CH2)rNR11fS(O)2R11b, and (CH2)rphenyl substituted with 0-3 R11e; R11d, at each occurrence, is selected from methyl, CF3, C2-6 alkyl substituted with 0-3 R11e, C3-6 alkenyl, C3-6 alkynyl, and a C3-10 carbocyclic residue substituted with 0-3 R11c; R11e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR11fR11f, and (CH2)rphenyl; R11f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R12 is selected from H, C1-6 alkyl, (CH2)qOH, (CH2)rC3-6 cycloalkyl, and (CH2)tphenyl substituted with 0-3 R12a; R12a, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR9fR9f, and (CH2)rphenyl; alternatively, R11 and R12 join to form C3-7 cycloalkyl; R14 is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, C(O)NR14aR14aâ€², C(O)R14b, C(O)OC1-4 alkyl, (CH2)rS(O)pR14b, (CH2)rphenyl substituted with 0-3 R14c, OR14a, NR14aR14aâ€², &boxH;O, and NR14aC(O)R14aâ€²; R14a and R14aâ€², at each occurrence, are selected from H, C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R14c, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R14c; R14b, at each occurrence, is selected from C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R14c, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R14c; and R14c, at each occurrence, is selected from C1-6 alkyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, (CH2)wphenyl; R15, at each occurrence, is selected from C1-8 alkyl, (CCH2)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CHRâ€²)rNR15aR15aâ€², (CHRâ€²)rOH, (CHRâ€²)rO(CHRâ€²)rR15d, (CHRâ€²)rSH, (CHRâ€²)rC(O)H, (CHRâ€²)rS(CHRâ€²)rR15d, (CHRâ€²)rC(O)OH, (CHRâ€²)rC(O)(CHRâ€²)rR15b, (CHRâ€²)rC(O)NR15aR15aâ€², (CHRâ€²)rNR15fC(O)(CHRâ€²)rR15b, (CHRâ€²)rNR15fC(O)NR15aR15aâ€², (CHRâ€²)rC(O)O(CHRâ€²)rR15d, (CHRâ€²)rOC(O))(CHRâ€²)rR15b, (CHRâ€²)rC(&boxH;NR15f)NR15aR15aâ€², (CHRâ€²)rNHC(&boxH;NR15f)NR15aR15aâ€², (CHRâ€²)rS(O)p(CHRâ€²)rR15b, (CHRâ€²)rS(O)2NR15aR15aâ€², (CHRâ€²)rNR15fS(O)2(CHRâ€²)rR15b, C1-6 haloalkyl, C2-8 alkenyl substituted with 0-3 Râ€², C2-8 alkynyl substituted with 0-3 Râ€², (CFIRâ€²)rphenyl substituted with 0-3 R15e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R15e; Râ€², at each occurrence, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, and (CH2)rphenyl substituted with R15e; R15a and R15aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R15e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R15e; R15b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-3 R15e, and (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R15e; R15d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R15e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R15e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R15e; R15e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR15fR15f, and (CH2)rphenyl; R15f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; R16, at each occurrence, is selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CHRâ€²)rNR16aR16aâ€², (CHRâ€²)rOH, (CHRâ€²)rO(CHRâ€²)rR16d, (CHRâ€²)rSH, (CHRâ€²)rC(O)H, (CHRâ€²)rS(CHRâ€²)rR16d, (CHRâ€²)rC(O)OH, (CHRâ€²)rC(O)(CHRâ€²)rR16b, (CHRâ€²)rC(O)NR16aR16aâ€², (CHRâ€²)rNR16fC(O)(CHRâ€²)rR16b, (CHRâ€²)rC(O)O(CHRâ€²)rR16d, (CHRâ€²)rOC(O)(CHRâ€²)rR16b, (CHRâ€²)rC(&boxH;NR16f)NR16aR16aâ€², (CHRâ€²)rNHC(&boxH;NR16f)NR16aR16aâ€², (CHRâ€²)rS(O)p(CHRâ€²)rR16b, (CHRâ€²)rS(O)2NR16aR16aâ€², (CHRâ€²)rNR16fS(O)2(CHRâ€²)rR16b, C1-6 haloalkyl, C2-8 alkenyl substituted with 0-3 Râ€², C2-8 alkynyl substituted with 0-3 Râ€², and (CHRâ€²)rphenyl substituted with 0-3 R16e; R16a and R16aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R16e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R16e; R16b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)rC3-6 carbocyclic residue substituted with 0-3 R16e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R16e; R16d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R16e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R16e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R16e; R16e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR16fR16f, and (CH2)rphenyl; R16f, at each occurrence, is selected from H, C1-5 alkyl, and C3-6 cycloalkyl, and phenyl; a is 0; b is 1; c is selected from 0, 1, and 2; d is selected from 0, 1, and 2, wherein c+d equals 2; provided that if b=1, c=1, and d=1 then E cannot be â€”(CR7R8)â€”(CR9CR10)vâ€”(CR11CR12)â€”; g is selected from 0, 1, 2 and 3; i is selected from 1, 2, 3, 4, and 5; v, at each occurrence, is independently selected from 0, 1, and 2; t, at each occurrence, is selected from 1 and 2; w, at each occurrence, is selected from 0 and 1; r, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; s, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5; q, at each occurrence, is selected from 1, 2, 3, 4, and 5; and p, at each occurrence, is selected from 1 and 2.