Patent ID: 6534535
Filing Date: 2003-03-18
Classification: C07D

Abstract:
A compound according to the formula: wherein:A is selected from the group consisting of: (a) C1-C6-alkyl; (b) C3-C8-cycloalkyl; â€”N(â€”R2,â€”R3â€”C(&boxH;Nâ€”R2)â€”, (â€”R2, â€”R3)Nâ€”C(&boxH;Nâ€”R2)â€”(â€”R2, â€”R3)Nâ€”C(&boxH;Nâ€”R2)â€”N(â€”Râ€”)â€”(d) phenyl, which is independently substituted with 0-2 R1 substituents; (e) naphthyl, which is independently substituted with 0-2 R1 substituents; and (f) a monocyclic or fused bicyclic heterocyclic ring system having from 5 to 10 ring atoms, wherein 1-4 ring atoms of the ring system are selected from the group consisting of N, O and S, and wherein the ring system may be substituted with 0-2 R1 substituents; R1 is selected from the group consisting of: Halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, R2â€”C(&boxH;Nâ€”R3)â€”, (â€”R2, â€”R3)Nâ€”C(&boxH;Nâ€”R2)â€”, â€”(CH2)mNR2R3, â€”C(&boxH;O)â€”N(â€”R2, â€”R3), â€”SO2N(â€”R2, â€”R3), â€”SO2R2, â€”CF3, â€”OR2, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C1-C4-alkyl, â€”CN C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl and â€”NO2; R2 and R3 are independently selected from the group consisting of: H, â€”OR2, â€”N(â€”R2, â€”R3), â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”C0-4alkylphenyl and â€”C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN, and â€”NO2; or R2 and R3 taken together can form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 5 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, C1-C4â€”alkyl, â€”CNâ€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl and â€”NO2; m is an integer of 0-2; Q is a member selected from the group consisting of: a direct link, â€”CH2â€”, â€”C(&boxH;O)â€”, â€”N(R4)â€”, â€”N(R4)CH2â€”, â€”C&boxH;N(R4)â€”, â€”C(&boxH;O)â€”N(R4)â€”, â€”N(R4)â€”C(&boxH;O)â€”, â€”SO2â€”, â€”Oâ€”, â€”SO2â€”N(R4)â€” and â€”N(R4)â€”SO2â€”; R4 is selected from the group consisting of: H, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”C0-4alkylphenyl and â€”C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN, and â€”NO2; D is a phenyl, which is independently substituted with 0-2 R1a substituents; R1a is selected from the group consisting of: Halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, (CH2)mNR2aR3a, SO2NR2aR3a, SO2R2a, CF3, OR2a, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; R2a and R3a are independently selected from the group consisting of: H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; M is a member selected from the group consisting of: â€”C(â€”R17,â€”R18)â€”C(&boxH;O)â€”, â€”C(â€”R17,â€”R17a)â€”C(â€”R18,â€”R18a)â€”, â€”C(â€”R17)&boxH;C(â€”R18)â€”, â€”C(&boxH;O)â€”C(&boxH;O)â€”and â€”C(&boxH;C(R17b, â€”R17c))â€”C(&boxH;O)â€”, wherein the first named atom of the chain is directly attached to D, and wherein D, M and the N atom attached to the last chain atom of M collectively form a bicyclic ring structure; R17, R17a, R18 and R18a are each independently selected from the group consisting of: hydrogen, halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, (CH2)mNR2R3, SO2NR2R3, SO2R2, CF3, OR2 , and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C1-C4-alkyl, â€”CN, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl and â€”NO2; R17b and R17c are each independently a member selected from the group consisting of: hydrogen, â€”halo, hydroxy, â€”C1-4alkyl, C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylâ€”C3-8cycloalkyl, â€”CN, â€”NO2, â€”(CH2)mNR2R3, â€”SO2NR2R3, â€”SO2R2, â€”CF3, â€”OR2, phenyl, and a 5-6 membered aromatic heterocyclic ring containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the cycloalkyl, the phenyl ring, or the aromatic heterocyclic ring may be independently replaced with a member selected from the group consisting of halo, C1-C4-alkyl, â€”CN, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl and â€”NO2; E is a member selected from the group consisting of: a direct link, â€”C(&boxH;O)â€”, â€”C(&boxH;O)â€”N(R5)â€”, â€”C(â€”R5a,â€”R6a)â€” and â€”C(â€”R5b,â€”R6b)â€”C(â€”R5c,â€”R6c)â€”; wherein R5, R5a, R6a, R5b, R6b, R5c and R6c are independently selected from the group consisting of: p2 H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, C0-4alkylheteroaryl, C1-4alkylCOOH and C1-4alkylCOOC1-4alkyl, wherein from 0-4 hydrogen atoms on the ring atoms of the phenyl, naphthyl and heteroaryl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”OH, â€”Oâ€”C1-4alkyl, â€”SH, â€”Sâ€”C1-4alkyl, â€”CN and â€”NO2; G is selected from the group consisting of: a direct link, â€”C(R7,R8)â€”, â€”C(R7a,R8a)â€”C(R7b,R8b)â€” and â€”C(R7c)&boxH;C(R8c)â€”; wherein R7, R8, R7a, R8a, R7b, R8b, R7c and R8 c are independently a member selected from the group consisting of: hydrogen, halogen, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkyl â€”C3-8cycloalkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, â€”OR9, â€”N(R9R10), â€”C0-4alkylCOOR9, â€”C0-4alkylC(&boxH;O)NR9R10, â€”C0-4alkylC(&boxH;O)OR9, â€”C0-4alkylC(&boxH;O)NR9â€”CH2â€”CH2â€”Oâ€”R10, â€”C0-4alkylC(&boxH;O)NR9(â€”CH2â€”CH2â€”Oâ€”R10â€”)2, â€”N(R9)COR10, â€”N(R9)C(&boxH;O)R10,â€”N(R9)SO2R10, a naturally occurring or synthetic amino acid side chain, and C0-4alkylheterocyclic ring having from 1 to 4 hetero ring atoms selected from the group consisting of N, O and S, CH2COOC1-4alkyl, CH2COOC1-4alkylphenyl and CH2COOC1-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the CO0-4alkylheterocyclic ring may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”OR9, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylâ€”C3-8cycloalkyl, â€”CN and â€”NO2; R9 and R10 are independently selected from the group consisting of: H, C1-4alkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, C3-8cycloalkyl, and C1-4alkylâ€”Oâ€”C1-4alkyl, C1-4alkylâ€”COOH wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylâ€”C3-8cycloalkyl, â€”CN and â€”NO2, and wherein R9 and R10 taken together can form a 5-8 membered heterocylic ring; J is a member selected from the group consisting of: a direct link, â€”Oâ€”, â€”Oâ€”C(â€”R11, â€”R11a)â€”, â€”Sâ€”, â€”S(&boxH;O)â€”, â€”S(&boxH;O)2â€”, â€”Sâ€”C(â€”R11, â€”R11a)â€”, â€”S(&boxH;O)â€”C(â€”R11, â€”R11a)â€”, â€”S(&boxH;O)2â€”(â€”R11, â€”R11a)â€”, â€”C(&boxH;O)â€”, â€”C(&boxH;O)â€”N(R11b)â€”, â€”N(R11b)â€”C(&boxH;O)â€”, â€”N(R11b)â€”, â€”N(R11b)â€”C(â€”R11, â€”R11a)â€” O and a monocyclic aromatic or non-aromatic heterocyclic ring having from 5 to 8 ring atoms, wherein 1-4 ring atoms of the ring system are selected from the group consisting of N, O and S, and wherein the ring system may be substituted with 0-2 R11 substituents; R11, R11a, R11b, and R11 are a member independently selected from the group consisting of: hydrogen, halo, â€”CF3, â€”CN, â€”NR9R10, â€”SO2Me, â€”NO2, â€”OH, â€”Oâ€”C1-4alkyl, â€”Oâ€”C2-6alkenyl, â€”Oâ€”Câ€”2-6alkynyl, â€”Oâ€”C3-8cycloalkyl, â€”Oâ€”C1-4alkyl, â€”Oâ€”C1-4alkyl, â€”Oâ€”C1-4alkylâ€”COOH, â€”Oâ€”C1-4alkyl-phenyl, â€”COOH, â€”C(&boxH;O)â€”Oâ€”C1-4alkyl, â€”C(&boxH;O)â€”Oâ€”C2-6alkenyl, â€”C(&boxH;O)â€”Oâ€”C2-6alkynyl, â€”C(&boxH;O)â€”Oâ€”C3-8cycloalkyl, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylâ€”C3-8cycloalkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, C0-4alkylC(&boxH;O)NR9R10, C0-4alkylC(&boxH;O)OR9, C0-4alkylheterocyclic ring having from 1 to 4 hetero ring atoms selected from the group consisting of N, O and S, CH2COOC1-4alkyl, CH2COOC1-4alkylphenyl and CH2COOC1-4alkylnaphthyl; wherein from 1-4 hydrogen atoms on the C0-4alkylheterocyclic ring may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkyl-phenyl, C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”OR9, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylâ€”C3-8cycloalkyl, â€”CN and â€”NO2; Y is a member selected from the group consisting of: (a) phenyl, which is independently substituted with 0-2 R1b substituents; (b) naphthyl, which is independently substituted with 0-2 R1b substituents; and (c) a monocyclic or fused bicyclic heterocyclic ring system having from 5 to 10 ring atoms, wherein 1-4 ring atoms of the ring system are selected from the group consisting of N, O and S, and wherein the ring system may be substituted with 0-2 R1b substituents; R1b is a member selected from the group consisting of: halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, NR2bR3b, SO2NR2bR3b, SO2R2b, CF3, OR2b, Oâ€”CH2â€”CH2â€”OR2b, Oâ€”CH2â€”COOR2b, N(R2b)â€”CH2â€”CH2â€”OR2b, N(â€”CH2â€”CH2â€”OR2b)2, N(R2b)â€”C(&boxH;O)R3b, N(R2b)â€”SO2â€”R3b, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkyl-phenyl, â€”CN and â€”NO2; R2b and R3b are independently selected from the group consisting of: H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”OR9, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; L is selected from the group consisting of: H, â€”CN, C(&boxH;O)NR12R13, â€”(CH2)nNR12R13, C(&boxH;NR12) NR12R13, OR12, â€”NR12C(&boxH;NR12)NR12R13, and NR12C(&boxH;NR12)â€”R13; n is an integer from 0 to 8; R12 and R13 are independently selected from the group consisting of: 14, â€”NR14R15, C1-4alkyl, C0-4alkylphenyl, C0-4alkylnaphthyl, COOC1-4alkyl, COOâ€”C0-4alkylphenyl and COOâ€”C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, â€”OH, â€”Oâ€”C1-4alkyl, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, and â€”NO2; R14 and R15 are independently selected from the group consisting of: H, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, C0-4alkylphenyl and C0-4alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, and â€”NO2; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof.