Patent ID: 6627629
Filing Date: 2003-09-30
Classification: A61P,C07D

Abstract:
A compound of formula (I): or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: M is selected from CH2, CHR5, CHR13, CR13R13, and CR5R13; Q is selected from CH2, CHR5, CHR13, CR13R13, and CR5R13; J and K are independently selected from CH2, CHR5, CHR6, CR6R6 and CR5R6; L is selected from CHR5 and CR5R6; Z is selected from O, S, NR1a, C(CN)2, CH(NO2), and CHCN; 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 G is selected from a bond, C&boxH;O, and SO2; Ring B is a 5, 6, or 7 membered saturated heterocyclic ring wherein one of the heterocycle ring atoms is selected from â€”NR9â€”, â€”Oâ€”, and â€”S(O)pâ€”, or two of the heterocycle ring atoms are selected from â€”NR9dC(O)â€”, â€”C(O)NR9dâ€”, â€”C(O)Oâ€”, â€”OC(O)â€”, â€”NR9dS(O)2â€”, and â€”S(O)2NR9d, the heterocycle ring being selected from piperidine, tetrahydropyran, tetrahydrothiopyran, tetrahydrothiopyran 1,1-dioxide, tetrahydrothiopyran 1-monooxide, piperidin-2-one, tetrahydropyran-2-one, [1,2]thiazinane 1,1-dioxide, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyrrolidin-2-one, dihydrofuran-2-one, and isothiazolidine 1,1-dioxide, and being optionally substituted by 0-2 R8; R1 and R2 are independently selected from H, C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, and (CH2)rC3-6 cycloalkyl; R3 is selected from methyl substituted with 0-1 R10, C2-8 alkyl substituted with 0-3 R7, C3-8 alkenyl substituted with 0-3 R7, C3-8 alkynyl substituted with 0-3 R7, C2 fluoroalkyl, C3-8 haloalkyl, a (CR3â€²R3â€³)râ€”C3-10 carbocyclic residue substituted with 0-5 R15 and a (CR3â€²R3â€³)r-5-19 membered heterocyclic system, wherein the heterocyclic system is selected from 1H-indazole, 2-pyrrolidonyl, 2H, 6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl, &bgr;-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H, 6H-1,5,2-dithiazinyl, dihydrofuran-2-one, dihydrofuro [2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidine 1,1-dioxide, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidin-2-one, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, Pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidin-2-one, pyrrolidinyl, Pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydropyranyl (THP), tetrahydroquinolinyl, tetrahydropyran-2-one, tetrahydrothiophenyl, 1-oxo-hexahydro-1&agr;4-thiopyranyl, 1,1-dioxo-hexahydro-1&agr;6-thiopyranyl, tetrahydrothiopyranyl (THTP), 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,1-dioxo-1&agr;6-[1,2]thiazinanyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, and xanthenyl; 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)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; 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 f yam 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 or is CR6R6 and R6 is cyano, or bonded to the carbon to which it is attached through a heteroatom, the other R6 is not cyano, or bonded to the carbon to which it is attached through a heteroatom; R7 is selected from NO2, CN, NR7aR7aâ€², OH, OR7d, C(O)H, C(O)OH, C(O)R7b, C(O)NR7aR7aâ€², NR7fC(O)OR7d, OC(O)NR7aR7aâ€², NR7fC(O)R7b, NR7fC(O)NR7fR7f, C(O)OR7d, OC(O)R7b, C(&boxH;NR7f)NR7aR7aâ€², NHC(&boxH;NR7f)NR7fR7f, S(O)pR7b, S(O)2R7aR7aâ€², NR7fS(O)2NR7b, C1-6 haloalkyl; R7a and R7aâ€², at each occurrence, are selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkenyl, 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 0-2 R7e; alternatively, R7a and R7aâ€², along with the N to which they are attached, join to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR7h, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R7b, at each occurrence, is selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, a (CH2)râ€”C3-6 carbocyclic residue substituted with 0-3 R7e, and (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R7e; R7d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R7e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R7e, and a (CH2)r5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R7e; R7e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 Cycloalkyl, C(O)C1-6 alkyl, C(O)OC1-6 alkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR7fR7f, (CH2)rphenyl, and a heterocycle substituted with 0-1 R7g, wherein the heterocycle is selected from imidazole, thiazole, oxazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, isoxazole, and tetrazole,; R7f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; R7g is selected from methyl, ethyl, acetyl, and CF3; R7h is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R7f, C(O)OR7i, and SO2R7i; R7i, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl; R8 is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-6 haloalkyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R8c, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R8c; R8a, at each occurrence, are selected from H, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R8e, and a (CH2)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R8e; R8b, 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 R8e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R8e; R8c, 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)rNR8fR8f, (CH2)rOH, (CH2)rOC1-4 alkyl, (CH2)rSC1-4 alkyl, (CH2)rC(O)OH, (CH2)rC(O)R8a, (CH2)rC(0)NR8fR8f, (CH2)rNR8fC(O)R8a, (CH2)rC(O)OC1-4 alkyl, (CH2)rOC(O)R8b, (CH2)rS(O)pR8b, (CH2)rS(O)2NR8fR8f, (CH2)rNR8fS(O)2R8b, and (CH2)rphenyl substituted with 0-3 R8e; R8e, 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)rSH, (CH2)rSC1-5 alkyl, (CH2)rNR8fR8f, and (CH2)rphenyl; R8f, at each occurrence, is selected from H, C1-6 alkyl, and C3-6 cycloalkyl; R9 is selected from H, CH3, C2-6 alkyl substituted with 0-3 R9a, C3-8 alkenyl, C3-8 alkynyl, C1-6 haloalkyl, (CHRâ€²)rC(O)C1-6 alkyl substituted with 0-3 R9j, (CHRâ€²)rC(O)OC1-6 alkyl substituted with 0-3 R9b, (CHRâ€²)rC(O)NR9dR9dâ€², (CHRâ€²)rS(O)2C1-6 alkyl, S(O)2C1-6 haloalkyl, (CHRâ€²)rS(O)2NR9dR9d, R9â€², (CHRâ€²)rC(O)R9â€², (CHRâ€²)rC(O)NR9dR9â€², (CHRâ€²)rS(O)2R9â€², and (CHRâ€²)rS(O)2NR9dR9â€²; R9â€², at each occurrence, is independently selected from (CHRâ€²)rC3-6 cycloalkyl substituted with 0-3 R9e, (CHRâ€²)rphenyl substituted with 0-3 R9c, (CHRâ€²)r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R9c, R9a, at each occurrence, is selected from CN, NO2, OC1-5 alkyl, CF3, OH, OC1-5 alkyl, OC (O)C1-5 alkyl, SC1-5 alkyl, S(O)pC1-5 alkyl, and NR9dR9dâ€²; R9b, at each occurrence, is selected from C3-6 cycloalkyl, CN, (CF2)rCF3, (CH2)qOC1-5 alkyl, (CH2)qOH, (CH2)qSC1-5 alkyl, (CH2)rS(O)pC1-5 alkyl, and (CH2)qNR9dR9dâ€²; R9c, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CHRâ€²)rC(O)C1-5 alkyl, (CHRâ€²)rC(O)OC1-5 alkyl, (CHRâ€²)rC(O)NR9dR9dâ€², (CH2)rOH, (CH2)rSC1-5 alkyl, (CH2)rS(O)pC1-5 alkyl, and (CH2)rNR9dR9dâ€²; provided that if R9c is attached to a carbon attached to the nitrogen on Ring B, then R9c is selected from (CH2)qOH, (CH2)qOC1-5 alkyl, (CH2)qSC1-5 alkyl, (CH2)qS(O)qC1-5 alkyl, and (CH2)qNR9dR9dâ€²; R9d and R9dâ€², at each occurrence, are independently selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; alternatively, R9d and R9dâ€², along with the N to which they are attached, join to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR9h, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; R9e, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CHRâ€²)rC(O)OC1-5 alkyl, (CHRâ€²)rC(O)NR9dR9dâ€², (CH2)rOH, (CH2)rSC1-5 alkyl, (CH2)rS(O)pC1-5 alkyl, and (CH2)rNR9dR9dâ€², or alternatively, two R9e on the same carbon atom form &boxH;O; R9h is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R9f, C(O)0R9i, and SO2R9i; R9i, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl; R9j, at each occurrence, is selected from C3-6 cycloalkyl, ON, (CF2)rCF3, (CH2)rOC1-5 alkyl, (CH2)rOH, (CH2)rSC1-5 alkyl, (CH2)rS(O)pC1-5 alkyl, and (CH2)rNR9dR9d; R10 is selected from C(O)H, C(O)OH, C(O)R10b, C(O)NR10aR10aâ€², C(O)OR10d, C(&boxH;NR10f)NR10aR10aâ€², S(O)R10b, S(O)2R10b, S(O)2NR10aR10aâ€²; 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 0-2 R10e; alternatively, R10a and R10aâ€², along with the N to which they are attached, join to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR10h, 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 0-3 R10e, and (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R10e; R10d, at each occurrence, is selected from C3-8 alkenyl, C3-8 alkynyl, methyl, CF3, C2-6 alkyl substituted with 0-3 R10e, a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-3 R10e, and a (CH2)r5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R10e; R10e, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, (CH2)rC3-6 cycloalkyl, C(O)C1-6 alkyl, C(O)OC1-6 alkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl, OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR10fR10f, (CH2)rphenyl, and a heterocycle substituted with 0-1 R10g, wherein the heterocycle is selected from imidazole, thiazole, oxazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, isoxazole, and tetrazole; R10f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; R10g is selected from methyl, ethyl, acetyl, and CF3; R10h is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R10f, C(O)OR10i and SO2R10i; R10i, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl; R13, at each occurrence, is selected from C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl, (CF2)wCF3, (CH2)qNR13aR13aâ€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; R15, at each occurrence, is selected from &boxH;O 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)rC(O)OH, (CHRâ€²)rC(O)(CHRâ€²)rR15b, (CHRâ€²)rC(O)NR15aR15aâ€², (CHRâ€²)rNR15fC(O)O(CHRâ€²)rR15d, (CHRâ€²)rOC(O)NR15aR15aâ€², (CHRâ€²)rNR15fC(O)(CHRâ€²)rR15b, (CHRâ€²)rNR15fC(O)NR15fR15f, (CHRâ€²)rC(O)0(CHRâ€²)rR15d, (CHRâ€²)rOC(O) (CHRâ€²)rR15b, (CHRâ€²)rC(&boxH;NR15f)NR15aR15aâ€², (CHRâ€²)rNHC(&boxH;NR15f)NR15fR15f, (CHRâ€²)rS(O)p(CHRâ€²)rR15b, (CHRâ€²)rS(p)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; Râ€², at each occurrence, is independently selected from H, C1-6 alkyl, C3-8 alkenyl, C3-8 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; alternatively, R15a and R15aâ€², along with the N to which they are attached, join to form a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR15h, 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)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, C(O)C1-6 alkyl, C(O)OC1-6 alkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkyl OH, SH, (CH2)rSC1-5 alkyl, (CH2)rNR15fR15f, (CH2)rphenyl, and a heterocycle substituted with 0-1 R15g, wherein the heterocycle is selected from imidazole, thiazole, oxazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, isoxazole, and tetrazole; R15f, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and phenyl; R15g is selected from methyl, ethyl, acetyl, and CF3; R15h is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R15f, C(O)OR15i and SO2R15i; R15i, at each occurrence, is selected from C1-6 alkyl, 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)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; alternatively, R16a and R16aâ€², along with the N to which they are attached, join to arm a 5-6 membered heterocyclic system containing 1-2 heteroatoms selected from NR16h, O, and S and optionally fused with a benzene ring or a 6-membered aromatic heterocycle; 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, C1-6 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; R16h is selected from H, C1-6 alkyl, C3-6 cycloalkyl, (CH2)rphenyl, C(O)R16f, C(O)OR16i, and SO2R16i; R16i, at each occurrence, is selected from C1-6 alkyl, C3-6 cycloalkyl; m, at each occurrence, is independently selected from 0, 1, and 2; t, at each occurrence, is independently selected from 1 and 2; w, at each occurrence, is independently selected from 0 and 1; r, at each occurrence, is independently selected from 0, 1, 2, 3, 4, and 5; q, at each occurrence, is independently selected from 1, 2, 3, 4, and 5; and p, at each occurrence, is independently selected from 0, 1, and 2.