Patent ID: 6624184
Filing Date: 2003-09-23
Classification: A61P,C07D

Abstract:
A compound of the following formula I, or a pharmaceutically acceptable salt thereof: wherein:R1 and R2 are each independently selected from the group consisting of H, F, Cl, Br, I, NO2, CF3, CN, OCF3, OH, C1-C4alkoxy-, C1-C4alkylcarbonyl-, C1-C6 alkyl, hydroxy C1-C4 alkyl-, C3-C6 alkenyl, C3-C6 alkynyl, C3-C10 cycloalkyl(C0-C4alkyl)-, H2N(C0-C4)alkyl-, R6 HN(C0-C4)alkyl-, R6R7N(C0-C4)alkyl-, R7S(C0-C4)alkyl-, R7S(O) (C0-C4)alkyl-, R7SO2(C0-C4)alkyl-, R6R7NSO2(C0-C4)alkyl-, HSO3, HO2C(C0-C4)alkyl-, R6O2C(C0-C4)alkyl-, and R6R7NCO(C0-C4)alkyl-, or R1 and R2, when on adjacent carbon atoms, and when taken together are methylenedioxy or ethylenedioxy; R5 is independently selected from H, F, Cl, Br, I, NO2, CN, CF3, OCF3, OH, C1-C4alkoxy-, hydroxyC1-C4 alkyl-, C1-C4 alkylcarbonyl-, CO2H, CO2R6, CONR6R7, NHR6, and NR6R7; R6 is selected from H, C1-C8 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic (C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, hydroxy C0-C4 alkyl, oxo, F, Cl, Br, CF3, NO2, CN, OCF3, NH2, NHR7, NR7R8, SR7, S(O)R7, SO2R7, SO2NR7R8, CO2H, CO2R7, and CONR7R8; R7 and R8 are each independently selected from H, C1-C8 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C1-C5 alkoxy)carbonyl, arylsulfonyl, aryl(C0-C4 alkyl)-, heterocyclic(C1-C5 alkoxy)carbonyl, heterocyclic sulfonyl and heterocyclic (C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, CN, and NO2; or R6 and R7, or R6 and R8, or R7 and R8, when both substituents are on the same nitrogen atom, do or do not form, with the nitrogen atom to which they are attached, a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl, said heterocycle is unsubstituted or substituted with 0-3 groups selected from oxo, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl)-, C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C0-C5 alkyl), heterocyclic(C0-C5 alkyl), aryl(C1-C5 alkoxy)carbonyl, heterocyclic(C1-C5 alkoxy)carbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, and heterocyclicsulfonyl, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, CN, and NO2; K is selected from â€”C(&boxH;O)â€” and â€”CHR9â€”; L is selected from â€”C(&boxH;O), â€”CHR9â€”, â€”CR10R11â€”, â€”CR10R11â€”(C&boxH;O), â€”HR15Câ€”CHR16â€”, and â€”R15C&boxH;CR16; R9 is selected from H, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R10 is selected from H, F, Cl, Br, C1-C6 alkoxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, CN, and NO2; R11 is selected from H, F, Cl, Br, OMe, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, CN, and NO2; or R10 and R11, when on the same carbon atom, do or do not form, with the carbon atoms to which they are attached, a 3-7 membered carbocyclic or 3-7 membered heterocyclic non-aromatic ring system, said carbocyclic or heterocyclic ring is unsubstituted or substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, hydroxy C0-C4 alkyl, oxo, F, Cl, Br, CF3, and NO2; R12 is selected from C1-C8 alkyl and monocyclic or bicyclic aryl(C0-C4 alkyl)-, wherein said aryl groups are substituted with 0-3 substituents independently selected from R14; and R13 is H; R14 is selected from H, C1-C10 alkyl, NO2, CF3, CN, F, Cl, Br, C1-C10 alkylcarbonyl, haloalkyl, haloalkoxy, OH, NR6R7(C0-C4 alkyl)-, R6 C(&boxH;O)O(C0-C4 alkyl)-, R6OC(&boxH;O)O (C0-C4 alkyl)-, R6O(0-C4 alkyl), R6R7 NC(&boxH;O)O (C0-C4 alkyl)-, R6R7 NC(&boxH;O) (C0-C4 alkyl)-, R6O(CR10R11)2-6R6NC(&boxH;O) (C0-C4 alkyl)-, R6R7N(CR10R11)2-6R6NC(&boxH;O) (C0-C4 alkyl)-, R6O2C(CH2)1-4O(C0-C4 akyl)-, R6OOC(C1-C4 alkoxy), â€”R6OOC(C0-C4 alkyl)-, R6C(&boxH;O)(C0-C4 alkyl)-, R6C(&boxH;O)NR7(C0-C4 alkyl)-, R6OC(&boxH;O)NR7(C0-C4 alkyl)-, R6OC(&boxH;NCN)NR7(C0-C4 alkyl)-, R6R7NC(&boxH;O)NR8(C0-C4 alkyl)-, R6OC(&boxH;NC) NR7(C0-C4 alkyl)-, R6(CR10R11)1-4 NR7C&boxH;Oâ€”, R6O (CR10R11)1-4O&boxH;CR7Nâ€”, NR6R7(CR10R11)1-4 C&boxH;O R7Nâ€”, R6O(CR10R11)2-4R7Nâ€”, R6O2C(CR10R11)1-4R7N, R6R7N (CR10R11)2-4R7Nâ€”, R6R7NC(&boxH;NCN)NR7(C0-C4 alkyl)-, R6R7NC(&boxH;C(H)(NO2))NR7(C0-C4 alkyl)-, R7R8N C(&boxH;NR7) NR7(C0-C4 alkyl)-, R6R7N SO2NR8(C0-C4 alkyl)-, R6SO2NR7(C0-C4 alkyl)-, R6R7N(C1-C4) COâ€”, R6R7N(C2-C6 alkyl)Oâ€”, R6CO(CR10R11)0-2 R7N(O2)S(C0-C4 alkyl), R6(O2)S R7 NC(&boxH;O) (C0-C4 alkyl)-, R6S(C0-C4 alkyl)-, R6S(&boxH;O) (C0-C4 alkyl)-, R6SO2(C0-C4 alkyl)-, SO2NR6R7, SiMe3, R6R7N(C2-C4alkyl)-, R6R7N (C2-C4 alkoxy)-, HSO3, HONHâ€”, R6ONHâ€”, R8R7NNR6â€”, HO(COR6)Nâ€”, HO(R6O2C)N, C2-C6 alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkylmethyl, aryl(C0-C4alkyl)-, heteroaryl(C0-C4alkyl)-, aryl(C0-C4alkyl)Oâ€”, and heteroaryl(C0-C4alkyl)Oâ€”, wherein said aryl groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R15 is selected from H, halo, cyano, C1-C8 alkyl, C3-C6 alkenyl, and C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from R14; and R16 is selected from H, halo, cyano, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl)-, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from R14; or when R15 and R16 are on adjacent carbon atoms, or when R15 and R16 are oriented on the same side of the double bond, as depicted in the following structure (III) R15 and R16 do or do not form, with the carbon atoms to which they are attached, a 3-7 membered carbocyclic aromatic or nonaromatic ring system, or a 3-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring is unsubstituted or substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R17 is selected from H, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, C1-C6 alkylcarbonyl, C1-C6 alkylsulfonyl, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, hydroxy(C2-C4)alkyl-, C1-C3 alkoxy(C2-C4)alkyl-, (C0-C4alkyl) (C0-C4 alkyl) amino(C2-C4)alkyl-, aryl(C0-C4 alkyl)-, aryl(C1-C5 alkoxy)carbonyl, arylsulfonyl, heterocyclic(C0-C4 alkyl), heterocyclic(C1-C5 alkoxy)carbonyl, and heterocyclicsulfonyl, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkoxy C1-C4 alkyl, oxo, F, Cl, Br, CF3, CN, and NO2; and R18 is selected from H, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl)-, aryl(C0-C4 alkyl)-, and heterocyclic(C0-C4 alkyl), wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, CN, and NO2; or R17 and R18, when both are on the same nitrogen atom, may form, with the nitrogen atom to which they are attached, a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl, said heterocycle may be substituted with 0-3 groups selected from oxo, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl)-, C1-C6 alkylcarbonyl, (C1-C6 alkylcarbonyl)(C0-C4alkyl)amino-, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C5 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C0-C5 alkyl), heterocyclic(C0-C5 alkyl), aryl(C1-C5 alkoxy)carbonyl, heterocyclic(C1-C5 alkoxy)carbonyl, C1-C6 alkylsulfonyl arylsulfonyl and heterocyclicsulfonyl, wherein said aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from CH3â€”, alkoxy, F, Cl, Br, CF3, CN, and NO2.