Patent ID: 6605623
Filing Date: 2003-08-12
Classification: A61P,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 and L are independently selected from CH2, CHR5, CHR6, CR6R6 and CR5R6; K is selected from CHR5 and CR5R6; Z is selected from O and S; E is â€”(CHR7)â€”(CHR9)vâ€”(CR11R12)â€”; R1 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; Ra, at each occurrence, is selected from C1-4 alkyl, C3-8 alkenyl, C3-8 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; alternatively, R2 and R3 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)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, or R11 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, or L 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 at each occurrence, is selected from H or alternatively R7 joins with R4 to form a 5, 6, or 7 membered piperidinium spirocycle or pyrrolidinium spirocycle substituted with 0-3Ra: R9 at each occurrence, is selected from H or alternatively R9 joins with R4 to form a 5, 6, or 7 membered piperidinium spirocycle or pyrrolidinium spirocycle substituted with 0-3Ra; R11 at each occurrence, is selected from H, C1-6alkyl, C3-8 alkenyl, C3-8 alkynyl, and a (CH2)râ€”C3-10 carbocyclic residue substituted with 0-5 R11c, or alternatively R11 joins with R4 to form a 5, 6, or 7 membered piperidinium spirocycle or pyrrolidinium spirocycle substituted with 0-3Ra; 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, C3-8 alkenyl, C3-8 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, (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; 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 H; 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)2NR3aR13aâ€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 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, (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; 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, 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 R15ea (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, 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)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; v is selected from 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 0, 1, and 2.