Patent ID: 6525069
Filing Date: 2003-02-25
Classification: C07D

Abstract:
A compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein:M is selected from CH2, CHR5, CHR13, CR13R13, and CR5R13; Q is selected from CH2, CHR5, CHR13, CR13R13, and CR5R13; J, K and L are independently selected from CH2, CHR5, CHR6, CR6R6 and CR5R6; with the proviso that at least one of J, K, or L contains R5; Z is selected from O, S, NR1a, CHCN, CHNO2, and C(CN)2; R1a is selected from H, C1-6 alkyl, C3-6 cycloalkyl, CONR1bR1b, OR1b, CN, NO2, and (CH2)wphenyl; R1b is independently selected from H, C1-3 alkyl, C3-6 cycloalkyl, and phenyl; E is selected from: ring A is a C3-6 carbocyclic residue, provided that the C3-6 carbocyclic residue in Ring A is not phenyl; R1 and R2 are independently selected from H, C1-6 alkyl, C3-8 alkenyl, and C3-8 alkynyl; R3 is selected from a C1-10 alkyl substituted with 0-5 R3g, C3-10 alkenyl substituted with 0-5 R3g, and C3-10 alkynyl substituted with 0-5 R3g; R3g, at each occurrence, is independently selected from Cl, Br, I, F, NO2, CN, NR3aR3aâ€², OH, O(CHRâ€²)rR3d, SH, C(O)H, S(CHRâ€²)rR3d, C(O)OH, C(O)(CHRâ€²)rR3b, C(O)NR3aR3aâ€², OC(O)NR3aR3aâ€², NR3aC(O)OR3d, NR3fC(O)(CHRâ€²)rR3b, C(O)O(CHRâ€²)rR3d, OC(O)(CHRâ€²)rR3b, C(&boxH;NR3f)NR3aR3aâ€², NHC(&boxH;NR3f)NR3fR3f, S(O)p(CHRâ€²)rR3b, S(O)2NR3aR3aâ€², NR3fS(O)2(CHRâ€²)rR3b, a C3-10 carbocyclic residue substituted with 0-5 R15, and a 5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R15, provided that when R3g is a carbocyclic residue or a heterocyclic system, R3 has at least one other R3g, which is not a carbocyclic residue or a heterocyclic system; R3a and R3aâ€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 R3e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R3e; R3b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-3 R3e, and (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R3e; R3d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R3e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R3e, and a (CH2)r5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R3e; R3e, 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)rS(O)pC1-5 alkyl, (CH2)rNR3fR3f, and (CH2)rphenyl; R3f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; R4 is absent, taken with the nitrogen to which it is attached to form an N-oxide, or selected from C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, (CH2)rC3-6 cycloalkyl, (CH2)qC(O)R4b, (CH2)qC(O)NR4aR4aâ€², (CH2)qC(O)OR4b, 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, C3-8 alkenyl, (CH2)rC3-6 cycloalkyl, C3-8 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; alternatively, R4 joins with R7, R9, R11, or R14 to form a 5, 6 or 7 membered piperidinium spirocycle or pyrrolidinium spirocycle substituted with 0-3 Ra; R5 is selected from a (CR5â€²R5â€³)tâ€”C3-10 carbocyclic residue substituted with 0-5 R16 and a (CR5â€²R5â€³)t-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R16; R5â€² and R5â€³, at each occurrence, are selected from H, C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and phenyl; R6, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, (CF2)rCF3, CN, (CH2)rNR6aR6aâ€², (CH2)rOH, (CH2)rOR6b, (CH2)rSH, (CH2)rSR6b, (CH2)rC(O)OH, (CH2)rC(O)R6b, (CH2)rC(O)NR6aR6aâ€², (CH2)rNR6dC(O)R6a, (CH2)rC(O) OR6b, (CH2)rOC(O)R6b, (CH2)rS(O)pR6b, (CH2)rS(O)2NR6aR6aâ€², (CH2)rNR6dS(O)2R6b, and (CH2)tphenyl substituted with 0-3 R6c; R6a and R6aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl substituted with 0-3 R6c; R6b, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, and phenyl substituted with 0-3 R6c; R6c, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CH2)rOH, (CH2)rSC1-5 alkyl, and (CH2)rNR6dR6d; R6d, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; with the proviso that when any of J, K or L is CR6R6 and R6 is bonded to the carbon to which it is attached through a heteroatom, the other R6 is not bonded to the carbon to which it is attached through a heteroatom; R7, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)qOH, (CH2)qSH, (CH2)qOR7d, (CH2)qSR7d, (CH2)qNR7aR7aâ€², (CH2)rC(O)OH, (CH2)rC(O)R7b, (CH2)rC(O)NR7aR7aâ€², (CH2)rOC(O)NR7aR7aâ€², (CH2)qNR7aC(O)OR7b, (CH2)qNR7aC(O)R7a, (CH2)qNR7aC(O)H, (CH2)rC(O)OR7b, (CH2)qOC(O)R7b, (CH2)qS(O)pR7b, (CH2)qS(O)2NR7aR7aâ€², (CH2)qNR7aS(O)2R7b, C1-6 haloalkyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R7c, and a (CH2)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, (CH2)rC3-6 cycloalkyl, 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; alternatively, R7a and R7aâ€², along with the N to which they are attached, are joined to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR7g, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R7b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 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)R7a, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R7b, (CH2)rC(&boxH;NR7f)NR7fR7f, (CH2)rS(O)pR7b, (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, C3-8 alkenyl, C3-8 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, (CH2)rSC1-5 alkyl, (CH2)rNR7fR7f, and (CH2)rphenyl; R7f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R7g is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R7f, C(O)OR7f, and SO2R7f; R8 is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)tphenyl 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; R8b is selected from H, C1-6 alkyl, C3-6 cycloalkyl, OH, CN, and (CH2)r-phenyl; alternatively, R7 and R8 join to form C3-7 cycloalkyl, &boxH;O or &boxH;NR8b; R9, is selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CH2)rOH, (CH2)rSH, (CH2)rOR9d, (CH2)rSR9d, (CH2)rNR9aR9aâ€²(CH2)rC(O)OH, (CH2)rC(O)R9b, (CH2)rC(O)NR9aR9aâ€², (CH2)rNR9aC(O)R9a, (CH2)rNR9aC(O)H, (CH2)rOC(O)NR9aR9aâ€², (CH2)rNR9aC(O)OR9b, (CH2)rNR9aC(O)NHR9a, (CH2)rC(O)OR9b, (CH2)rOC(O)R9b, (CH2)rS(O)pR9b, (CH2)rS(O)2NR9aR9aâ€², (CH2)rNR9aS(O)2R9b, C1-6 haloalkyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R9c, and a (CH2)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, substituted with 0-3 R9e; alternatively, R9a and R9aâ€², along with the N to which they are attached, are joined to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR9g, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R9b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 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)R9a, (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 C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, a C3-10 carbocyclic residue substituted with 0-3 R9c, 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 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; R9g is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R9f, C(O)OR9f, and SO2R9f; 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)OR10b, (CH2)rOC(O)R10b, (CH2)rOC(O)NR10aR10aâ€², (CH2)rNR10aC(O)OR10b, (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 0-5 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; alternatively, R10a and R10aâ€², along with the N to which they are attached, are joined to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR10g, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R10b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 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 C1-6 alkyl, 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, C1-5 alkyl, and C3-6 cycloalkyl; R10g is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R10f, C(O)OR10h, and SO2R10h; R10h, at each occurrence, is selected from C1-5 alkyl, and C3-6 cycloalkyl; alternatively, R9 and R10 join to form &boxH;O, a C3-10 cycloalkyl, a 5-6-membered lactone or lactam, or a 4-6-membered saturated heterocycle containing 1-2 heteroatoms selected from O, S, and NR10g and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; with the proviso that when either of R9 or R10 is halogen, cyano, nitro, or bonded to the carbon to which it is attached through a heteroatom, the other of R9 or R10 is not 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)R11a, (CH2)qOC(O)NR11aR11aâ€², (CH2)qNR11aC(O)OR11b, (CH2)(NR11aC(O)NHR11a, (CH2)rC(O)OR11b, (CH2)qOC(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 membered 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; alternatively, R11a and R11aâ€², along with the N to which they are attached, are joined to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR11g, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R11b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-2R11e, 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, (CH2)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 thulle, 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; R11g is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R11f, C(O)OR11h, and SO2R11h; R11h, at each occurrence, is selected from C1-5 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 a C3-10 cycloalkyl, a 5-6-membered lactone or lactam, or a 4-6-membered saturated heterocycle containing 1-2 heteroatoms selected from O, S, and NR11g and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R13, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, (CF2)wCF3, (CH2)NR13aR13aâ€², (CH2)qOH, (CH2)qOR13b, (CH2)qSH, (CH2)qSR13b, (CH2)wC(O)OH, (CH2)wC(O)R13b, (CH2)wC(O)NR13aR13aâ€², (CH2)qNR13dC(O)R13a, (CH2)wC(O)OR13b, (CH2)qOC(O)R13b, (CH2)wS(O)pR13b, (CH2)wS(O)2NR13aR13aâ€², (CH2)qNR13dS(O)2R13b, and (CH2)w-phenyl substituted with 0-3 R13c; R13a and R13aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl substituted with 0-3 R13c; R13b, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, and phenyl substituted with 0-3 R13c; R13c, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CH2)rOH, (CH2)rSC1-5 alkyl, and (CH2)rNR13dR13d; R13d, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R14, at each occurrence, is selected from C1-6 alkyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CHRâ€²)rNR14aR14aâ€², (CHRâ€²)rOH, (CHRâ€²)rO(CHRâ€²)rR14d, (CHRâ€²)rSH, (CHRâ€²)rC(O)H, (CHRâ€²)rS(CHRâ€²)rR14d, (CHRâ€²)rC(O)OH, (CHRâ€²)rC(O)(CHRâ€²)rR14b, (CHRâ€²)rC(O)NR14aR14aâ€², (CHRâ€²)rNR14fC(O)(CHRâ€²)rR14b, (CHRâ€²)rC(O)O(CHRâ€²)rR14d, (CHRâ€²)rOC(O)(CHRâ€²)rR14b, (CHRâ€²)rC(&boxH;NR14f)NR14aR14aâ€², (CHRâ€²)rNHC(&boxH;NR14f)NR14fR14f, (CHRâ€²)rS(O)p(CHRâ€²)rR14b, (CHRâ€²)rS(O)2NR14aR14aâ€², (CHRâ€²)rNR14fS(O)2(CHRâ€²)rR14b, C1-6 haloalkyl, C2-8 alkenyl substituted with 0-3 Râ€², C2-8 alkynyl substituted with 0-3 Râ€², (CHRâ€²)rphenyl substituted with 0-3 R14e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R14e, or two R14 substituents on adjacent atoms on ring A form to join a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from N, O, and S substituted with 0-2 R14e; 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 R14e, ; R14a and R14aâ€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 R14e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R14e; R14b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-3 R14e, and (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R14e; R14d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R14e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R14e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R14e; R14e, 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)rNR14fR14f, and (CH2)rphenyl; R14f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; alternatively, R14 joins with R4 to form a 5, 6 or 7 membered piperidinium spirocycle or pyrrolidinium spirocycle fused to ring A, the spirocycle substituted with 0-3 Ra; Ra, 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)rNRbRb, (CH2)rOH, (CH2)rORc, (CH2)rSH, (CH2)rSRc, (CH2)rC(O)Rb, (CH2)rC(O)NRbRb, (CH2)rNRbC(O)Rb, (CH2)rC(O)ORb, (CH2)rOC(O)Rc, (CH2)rCH(&boxH;NRb)NRbRb, (CH2)rNHC(&boxH;NRb)NRbRb, (CH2)rS(O)pRc, (CH2)rS(O)2NRbRb, (CH2)rNRbS(O)2Rc, and (CH2)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; R15, at each occurrence, is selected from C1-8 alkyl, (CH2)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)NR15fR15f, (CHRâ€²)rC(O)O(CHRâ€²)rR15d, (CHRâ€²)rOC(O)(CHRâ€²)rR15b, (CH2)rOC(O)NR15aR15aâ€², (CH2)rNR15aC(O)OR15b, (CHRâ€²)rC(&boxH;NR15f)NR15aR15aâ€²(CHRâ€²)rNHC(&boxH;NR15f)NR15fR15f, (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, (CHRâ€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; 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; alternatively, R15a and R15aâ€², along with the N to which they are attached, are joined to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR15g, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R15b, at each occurrence, is selected from C1-6 alkyl, C3-8 alkenyl, C3-8 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; R15g is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R15f, C(O)OR15h, and SO2R15h; R15h, at each occurrence, is selected from C1-5 alkyl, and C3-6 cycloalkyl; 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)NR16fR16f, (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, C3-8 alkenyl, C3-8 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; g is selected from 0, 1, 2, 3, and 4; t is selected from 1 and 2; w is selected from 0 and 1; r is selected from 0, 1, 2, 3, 4, and 5; q is selected from 1, 2, 3, 4, and 5; and p is selected from 0, 1, and 2.