Patent ID: 6399627
Filing Date: 2002-06-04
Classification: A61P,C07C,C07D

Abstract:
A compound of the formula: wherein:A is selected from: (a) phenyl, which is independently substituted with 0-2 R substituents; (b) naphthyl, which is independently substituted with 0-2 R substituents; and (c) an aromatic or non-aromatic monocyclic heterocyclic ring system having from 5 to 8 ring atoms, wherein 1-4 ring atoms of the ring system are selected from N, O and S, and wherein the ring system may be substituted with 0-2 R substituents; â€ƒR is selected from: halo, â€”C1-4alkyl substituted by up to 4 of the same or different halogen atoms selected independently from the group consisting of chlorine, bromine, iodine and fluorine atoms, â€”C1-4alkyl, â€”C1-4alkyl-phenyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, â€”(CH2)mNR1R2, â€”SO2NR1R2, â€”SO2R1, â€”C(&boxH;O)â€”NR1R2, â€”CF3, â€”OR1, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, wherein from 1-4 hydrogen ring atoms on the aromatic heterocyclic system, or on the phenyl portion of the â€”C1-4alkyl-phenyl group, may be independently replaced with a member selected from the group consisting of halo, â€”C1-C4-alkyl, â€”CN, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”NH2; â€”N(â€”C1-4alkyl, â€”C0-4alkyl), and â€”NO2; â€ƒR1 and R2 are independently 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, â€”C(&boxH;O)â€”OH, â€”C(&boxH;O)â€”Oâ€”C1-6alkyl, â€”C(&boxH;O)â€”NH2, â€”C(&boxH;O)â€”N(â€”C1-4alkyl, â€”C0-4alkyl), or R1 and R2 combine with the nitrogen atom to which they are attached to form a 5-8 membered saturated, unsaturated or partially unsaturated heterocyclic ring containing from 0-2 further heteroatoms selected from N, O and S, wherein from 1-4 hydrogen ring atoms on the heterocyclic ring may be independently replaced with a member selected from the group consisting of halo, â€”C1-C4-alkyl, â€”CN, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”NH2; â€”N(â€”C1-4alkyl, â€”C0-4alkyl), and â€”NO2; â€ƒm is an integer of 0-2; B is a direct link; â€ƒR3, R3a and R3b are each independently 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 member selected from the group consisting of: (a) phenyl, which is independently substituted with 0-2 Ra substituents; and (b) an aromatic six-membered heterocyclic ring having from 1-2 ring nitrogen atoms, and wherein the ring atoms may be substituted with 0-2 Ra substituents; â€ƒRa is selected from: halo, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, â€”(CH2)nNR1aR2a, â€”SO2NR1aR2a, â€”SO2R1a, â€”CF3, â€”SR1a, â€”OR1a, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from 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, â€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN and â€”NO2; â€ƒn is an integer of 0-2; â€ƒR1a and R2a are independently 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; G1 and G2 are each independently a member selected from the group consisting of: hydrogen, halo, â€”C1-6alkyl, haloalkyl, â€”CN, â€”NO2, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylâ€”C3-8-cycloalkyl, â€”C0-4alkyl-CN, â€”C0-4alkyl-NO2, â€”C0-4alkyl-Oâ€”R4, â€”C0-4alkyl-Sâ€”R4, â€”C0-4alkyl-S(&boxH;O)2â€”R4, â€”C0-4alkyl-S(O)â€”R4, â€”C0-4alkyl-C(&boxH;O)â€”OR4, â€”C0-4alkyl-C(&boxH;O)â€”N(R4a,R4b), â€”C0-4alkyl-C(&boxH;O)â€”R4, â€”C0-4alkyl-N(R4a,R4b), â€”C0-4alkyl-N(â€”R4a)â€”C(&boxH;O)â€”R4b), â€”C0-4alkyl-N(â€”R4a)â€”C(&boxH;O)â€”R4b, â€”C0-4alkyl-N(â€”R4a)â€”C(&boxH;O)â€”N(â€”R4b), â€”C0-4alkyl-N(â€”R4a)â€”S(&boxH;O)2â€”R4b, â€”C0-4alkyl-S(&boxH;O)2â€”N(R4a,R4b), â€”C0-4alkyl-S(&boxH;O)2â€”R4, â€”C0-4alkyl-P(&boxH;O)(â€”OR4a)(â€”OR4b), â€”C0-4alkyl-N(â€”R4)-P(&boxH;O)(â€”OR4a)(â€”OR4b), â€”C0-4alkyl-phenyl, â€”C0-4alkyl-naphthyl, â€”C0-4alkyl-heterocyclic ring system containing from 1-4 heteroatoms selected from the group consisting of O, N and S, wherein the heterocyclic ring system is a 5-6 membered monocyclic ring or a 8-12 membered bicyclic ring, and wherein 0-4 hydrogen atoms of the phenyl ring, the naphthyl ring carbon and the heterocyclic ring system are replaced by a member selected from the group consisting of â€”C1-4alkyl, haloalkyl, halo, â€”CN, â€”NO2, â€”OR4c, â€”SR4c, â€”S(O)R4c, â€”C(&boxH;O)â€”OR4c, â€”C(&boxH;O)â€”N(â€”R4c,R4d), â€”C(&boxH;O)â€”R4c, â€”N(R4c,R4d), â€”N(â€”R4c)â€”C(&boxH;O)â€”R4d, â€”N(â€”R4c)â€”C(&boxH;O)â€”OR4d, â€”N(â€”R4c)â€”C(&boxH;O)â€”N(â€”H,R4d), â€”N(â€”R4c)â€”SO2â€”R4d, â€”SO2â€”N(â€”R4c,â€”R4d), â€”SO2â€”R4c; or G1 and a nitrogen on the E group can combine to form a 5-7 membered heterocyclic ring containing a 0-3 additional heteroatoms selected from the group consisting of O, N and S; â€ƒR4, R4a, R4b, R4c and R4d are each independently a member selected from the group consisting of: H, halo â€”C1-6alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkyl-C3-8cycloalkyl, â€”CH2CH2OH, â€”CH2CH2â€”Oâ€”CH3, â€”C0-4alkylphenyl, â€”C0-4alkylheterocycle wherein the heterocycle may be a 5-6 membered ring, and wherein from 0-4 hydrogen atoms from the ring atoms of the phenyl and heterocycle groups 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€”C0-4alkyl-C3-8cycloalkyl, â€”CN, â€”NO2, â€”C(&boxH;O)â€”OH, â€”C(&boxH;O)â€”Oâ€”C1-4alkyl, â€”C(&boxH;O)â€”NH2, â€”C(&boxH;O)â€”N(â€”H, â€”C1-4alkyl), and â€”C(&boxH;O)â€”N(â€”C1-4alkyl, â€”C1-4alkyl); alternatively, R4a taken with R4b or R4c taken with R4d when either pair of groups is attached to the same nitrogen atom may combine with that nitrogen atom to form a 5-8 membered saturated, partially saturated or unsaturated ring which contains from 0-1 additional heteroatoms selected from a group consisting of â€”N, â€”O, S, wherein any S ring atom may be present as a â€”Sâ€”, â€”S(&boxH;O)â€” or â€”S(&boxH;O)2â€” group; E is â€”N(R5)â€”C(&boxH;O)â€”; â€ƒwherein R5, R6, R5a, R6a, R5b R6b, R5c and R6c are each independently selected from: H, â€”OH, â€”Oâ€”C1-4alkyl, â€”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, C-04alkylC3-8cycloalkyl, â€”OH, â€”Oâ€”C1-4alkyl, â€”SH, â€”Sâ€”C1-4alkyl, â€”CN and â€”NO2; K is a member selected from the group consisting of: (a) phenyl, which is independently substituted with 0-2 Rb substituents; (b) naphthyl, which is independently substituted with 0-2 Rb substituents; and (c) a monocyclic or used bicyclic heterocyclic ring system having from 5 to 10 ring atoms, wherein 1-4 ring atoms of the ring system are selected from N, O and S, and wherein the ring system may be substituted with 0-2 Rb substituents; â€ƒRb is a member selected from the group consisting of: halo, C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C0-4alkylC3-8cycloalkyl, â€”CN, NR1bR2b, SO2NR1bR2b, SO2R1b, CF3, OR1b, Oâ€”CH2â€”CH2â€”OR1b, Oâ€”CH2â€”COOR1b, N(R1b)â€”CH2â€”CH2â€”OR1b, N(â€”CH2â€”CH2â€”OR1b)2, N(R1b)â€”C(&boxH;O)R2b, N(R1b)â€”SO2â€”R2b, and a 5-6 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from 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; â€ƒR1b and R2b 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; L is selected from: H, â€”CN, C(&boxH;O)NR12R13, (CH2)nNR12R13, â€”C(&boxH;NR12)NR12R13, â€”CH&boxH;Nâ€”N(â€”R12)â€”C(&boxH;NR12a, â€”N(â€”R12b,â€”R12c), â€”OR12, â€”NR12C(&boxH;NR12)NR12R13, and NR12C(&boxH;NR12)â€”R13; â€ƒR12, R12a, R12b, R12c and R13 are independently selected from: hydrogen, â€”OR14, 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; â€ƒR14 and R15 are independently selected from: H, C1-4alkyl, â€”C(&boxH;O)â€”Oâ€”C0-6alkyl, â€”C(&boxH;O)â€”NH2, â€”C(&boxH;O)â€”N(â€”H, â€”C1-6alkyl) â€”C(&boxH;O)â€”N(â€”C1-6alkyl, â€”C1-6alkyl), â€”C(&boxH;O)â€”N(â€”H, â€”C1-6alkyl-N(â€”C1-6alkyl, â€”C1-6alkyl)), â€”C(&boxH;O)â€”N(â€”C1-6alkyl, â€”C1-6alkyl-N(â€”C1-6alkyl, â€”C1-6alkyl)), â€”C(&boxH;O)â€”([N,N]-piperazino-C1-6alkyl), â€”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€”C1-4alkyl, â€”C2-6alkenyl, â€”C2-6alkynyl, â€”C3-8cycloalkyl, â€”C0-4alkylC3-8cycloalkyl, â€”CN, â€”NO2, and â€”COOâ€”C0-4alkyl; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof.