Heterocyclic piperidines as modulators of chemokine receptor activity

A compound of formula I:

• 66
• or stereoisomers or pharmaceutically acceptable salts thereof, wherein:
• M is absent or 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 provisos:
• 1) at least one of M, J, K, L, or Q contains an R5;
• and
• 2) when M is absent, J is selected from CH2, CHR5, CHR13, and CR5R13;
• E is —(CR7R8)—(CR9R10)v—;
• Y is selected from:
• 67
• X is selected from NR14, O, and S;
• Z is selected from C(O)R3, S(O)2R3, C(O)OR3, C(O)NR2R3, C(═NR1)NR2R3, C(═CHCN)NR2R3, C(═CHNO2)NR2R3, C(═C(CN)2)NR2R3, and (CR′R′)t-phenyl substituted with 0-5 R15;
• R′, 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;
• R1 is selected from H, C1-6 alkyl, C3-6 cycloalkyl, OH, CN, and (CH2)wphenyl;
• R2 is selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, and a (CH2)r-C3-10 carbocyclic residue substituted with 0-5 R2a;
• R2a, at each occurrence, is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, (CF2)rCF3, NO2, CN, (CH2)rNR2bR2b, (CH2)rOH, (CH2)rOR2c, (CH2)rSH, (CH2)rSR2c, (CH2)rC(O)R2b, (CH2)rC(O)NR2bR2b, (CH2)rNR2bC(O)R2b, (CH2)rC(O)OR2b, (CH2)rOC(O)R2c, (CH2)rCH(═NR2b)NR2bR2b, (CH2)rNHC(═NR2b)NR2bR2b, (CH2)rS(O)pR2c, (CH2)rS(O)2NR2bR2b, (CH2)rNR2bS(O)2R2c, and (CH2)rphenyl;
• R2b, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl;
• R2c, at each occurrence, is selected from C1-5 alkyl, C3-6 cycloalkyl, and phenyl;
• R3 is selected from a CR3′R3″R3″, (CR3′R3″)r—C3-10 carbocyclic residue substituted with 0-5 R15 and a (CR3′R3″)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R15;
• R3′ and R3″, 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, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, (CH2)qC(O)R4b, (CH2)qC(O)NR4aR4a′, (CH2)qC(O)OR4b, and a (CH2)r—C3-10 carbocyclic residue substituted with 0-3 R4c;
• R4a and R4a′, 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)rNR4aR4a′, and (CH2)rphenyl;
• R5 is selected from a (CR5′R5″)t—C3-10 carbocyclic residue substituted with 0-5 R16 and a (CR5′R5″)t-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R16;
• R5′ and R5″, at each occurrence, are selected from H, C1-6 alkyl, (CH2)rC3-6 cycloalkyl, and phenyl;
• R6, at each occurrence, is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, (CF2)rCF3, CN, (CH2)rNR6aR6a′, (CH2)rOH, (CH2)rOR6b, (CH2)rSH, (CH2)rSR6b, (CH2)rC(O)OH, (CH2)rC(O)R6b, (CH2)rC(O)NR6aR6a′, (CH2)rNR6dC(O)R6a, (CH2)rC(O)OR6b, (CH2)rOC(O)R6b, (CH2)rS(O)pR6b, (CH2)rS(O)2NR6aR6a′, (CH2)rNR6dS(O)2R6b, and (CH2)tphenyl substituted with 0-3 R6c;
• R6a and R6a′, 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;
• R7 is selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)qOH, (CH2)qSH, (CH2)qOR7d, (CH2)qSR7d, (CH2)qNR7aR7a′, (CH2)rC(O)OH, (CH2)rC(O)R7b, (CH2)rC(O)NR7aR7a′, (CH2)qNR7aC(O)R7a, (CH2)rC(O)OR7b, (CH2)qOC(O)R7b, (CH2)qS(O)pR7b, (CH2)qS(O)2NR7aR7a′, (CH2)qNR7aS(O)2R7b, C1-6 haloalkyl, a (CH2)r—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 R7a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, a (CH2)r—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)r—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 C1-4 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(═NR7f)NR7fR7f, (CH2)rS(O)pR7b, (CH2)rNHC(═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 C1-6 alkyl substituted with 0-3 R7e, alkenyl, 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, C1-5 alkyl, and C3-6 cycloalkyl;
• 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;
• alternatively, R7 and R8 join to form C3-7 cycloalkyl, or ═NR8b;
• R8b is selected from H, C1-6 alkyl, C3-6 cycloalkyl, OH, CN, and (CH2)r-phenyl;
• R9 is independently selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CH2)rOH, (CH2)rSH, (CH2)rOR9d, (CH2)rSR9d, (CH2)rNR9aR9a′, (CH2)rC(O)OH, (CH2)rC(O)R9b, (CH2)rC(O)NR9aR9a′, (CH2)rNR9aC(O)R9a, (CH2)rNR9aC(O)H, (CH2)rC(O)OR9b, (CH2)rOC(O)R9b, (CH2)rS(O)pR9b, (CH2)rS(O)2NR9aR9a′, (CH2)rNR9aS(O)2R9b, C1-6 haloalkyl, a (CH2)r—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;
• R9′ is independently selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CH2)rOH, (CH2)rSH, (CH2)rOR9d, (CH2)rSR9d, (CH2)rNR9aR9a′, (CH2)rC(O)OH, (CH2)rC(O)R9b, (CH2)rC(O)NR9aR9a′, (CH2)rNR9aC(O)R9a, (CH2)rNR9aC(O)H, (CH2)rC(O)OR9b, (CH2)rOC(O)R9b, (CH2)rS(O)pR9b, (CH2)rS(O)2NR9aR9a′, (CH2)rNR9aS(O)2R9b, C1-6 haloalkyl, (CH2)r—C3-6 cycloalkyl, (CH2)q-phenyl substituted with 0-5 R9c, and a (CH2)q-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R9c;
• R9a and R9a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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;
• R9b, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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 C1-4 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(═NR9f)NR9fR9f, (CH2)rS(O)pR9b, (CH2)rNHC(═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, C2-6 alkenyl, C2-6 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, C1-5 alkyl, and C3-6 cycloalkyl;
• R10 is independently selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, F, Cl, Br, I, NO2, CN, (CH2)rOH, (CH2)rOR10d, (CH2)rSR10d, (CH2)rNR10aR10a′, (CH2)rC(O)OH, (CH2)rC(O)R10b, (CH2)rC(O)NR10aR10a′, (CH2)rNR10aC(O)R10a, (CH2)rNR10aC(O)H, (CH2)rC(O)OR10b, (CH2)rOC(O)R10b, (CH2)rS(O)pR10b, (CH2)rS(O)2NR10aR10a′, (CH2)rNR10aS(O)2R10b, C1-6 haloalkyl, a (CH2)r—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 R10a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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)r—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 C1-4 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(═NR10f)NR10fR10f, (CH2)rS(O)pR10b, (CH2)rNHC(—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, C2-6 alkenyl, C2-6 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;
• with the proviso that when R10 is —OH, R9 is not halogen, cyano, or bonded to the carbon to which it is attached through a heteroatom;
• alternatively, R9 and R10 join to form C3-7 cycloalkyl;
• R11 is selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)qOH, (CH2)qSH, (CH2)qOR11d, (CH2)qSR11d, (CH2)qNR11aR11a′, (CH2)rC(O)OH, (CH2)rC(O)R11b, (CH2)rC(O)NR11aR11a′, (CH2)qNR11aC(O)R11a, (CH2)rC(O)OR11b, (CH2)qOC(O)R11b, (CH2)qS(O)pR11b, (CH2)qS(O)2NR11aR11a′, (CH2)qNR11aS(O)2R11b, C1-6 haloalkyl, a (CH2)r—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;
• R11′ is selected from H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)qOH, (CH2)qSH, (CH2)qOR11d, (CH2)qSR11d, (CH2)qNR11aR11a′, (CH2)rC(O)OH, (CH2)rC(O)R11b, (CH2)rC(O)NR11aR11a′, (CH2)qNR11aC(O)R11a, (CH2)rC(O)OR11b, (CH2)qOC(O)R11b, (CH2)qS(O)pR11b, (CH2)qS(O)2NR11aR11a′, (CH2)qNR11aS(O)2R11b, C1-6 haloalkyl, a (CH2)r—C3-6 cycloalkyl, (CH2)q-phenyl substituted with 0-5 R11c, and a (CH2)q-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R11c;
• R11a and R11a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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)r—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 C1-4 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(═NR11f)NR11fR11f, (CH2)rNHC(═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 C1-6 alkyl substituted with 0-3 R11e, C2-6 alkenyl, C2-6 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, C1-5 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;
• R13, at each occurrence, is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, (CF2)wCF3, (CH2)qNR13aR13a′, (CH2)qOH, (CH2)qOR13b, (CH2)qSH, (CH2)qSR13b, (CH2)wC(O)OH, (CH2)wC(O)R13b, (CH2)wC(O)NR13aR13a′, (CH2)qNR13dC(O)R13a, (CH2)wC(O)OR13b, (CH2)qOC(O)R13b, (CH2)wS(O)pR13b, (CH2)wS(O)2NR13aR13a, (CH2)qNR13dS(O)2R13b, and (CH2)w-phenyl substituted with 0-3 R13c;
• R13a and R13a′, 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 is selected from C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, C(O)NR14aR14a′, C(O)R14b, C(O)OC1-4 alkyl, (CH2)rS(O)pR14b, (CH2)rphenyl substituted with 0-3 R14c;
• R14a and R14a′, 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, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, Cl, Br, I, F, NO2, CN, (CHR′)rNR15aR15a′, (CHR′)rOH, (CHR′)rO(CHR′)rR15d, (CHR′)rSH, (CHR′)rC(O)H, (CHR′)rS(CHR′)rR15d, (CHR′)rC(O)OH, (CHR′)rC(O)(CHR′)rR15b, (CHR′)rC(O)NR15aR15a′, (CHR′)rNR15fC(O)(CHR′)rR15b, (CHR′)rC(O)O(CHR′)rR15d, (CHR′)rOC(O)(CHR′)rR15b, (CHR′)rC(═NR15f)NR15aR15a′, (CHR′)rNHC(═NR15f)NR15fR15f, (CHR′)rS(O)p(CHR′)rR15b, (CHR′)rS(O)2NR15aR15a′, (CHR′)rNR15fS(O)2(CHR′)rR15b, C1-6 haloalkyl, C2-8 alkenyl substituted with 0-3 R′, C2-8 alkynyl substituted with 0-3 R′, (CHR′)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 R15a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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)r—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 C2-8 alkenyl, C2-8 alkynyl, C1-6 alkyl substituted with 0-3 R15e, a (CH2)r—C3-10 carbocyclic residue substituted with 0-3 R15e, and a (CH2)r5-6 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, C1-5 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, (CHR′)rNR16aR16a′, (CHR′)rOH, (CHR′)rO(CHR′)rR16d, (CHR′)rSH, (CHR′)rC(O)H, (CHR′)rS(CHR′)rR16d, (CHR′)rC(O)OH, (CHR′)rC(O)(CHR′)rR16b, (CHR′)rC(O)NR16aR16a′, (CHR′)rNR16fC(Q)(CHR′)rR16b, (CHR′)rC(O)O(CHR′)rR16d, (CHR′)rOC(O)(CHR′)rR16b, (CHR′)rC(═NR16f)NR16aR16a′, (CHR′)rNHC(═NR16f)NR16fR16f, (CHR′)rS(O)p(CHR′)rR16b, (CHR′)rS(O)2NR16aR16a′, (CHR′)rNR16fS(O)2(CHR′)rR16b, C1-6 haloalkyl, C2-8 alkenyl substituted with 0-3 R′, C2-8 alkynyl substituted with 0-3 R′, and (CHR′)rphenyl substituted with 0-3 R16e;
• R16a and R16a′, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)r—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 C2-8 alkenyl, C2-8 alkynyl, C1-6 alkyl substituted with 0-3 R16e, a (CH2)r—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;
• v is selected from 0, 1, and 2;
• 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 1, 2, and 3.