Patent ID: 6365589
Filing Date: 2002-04-02
Classification: C07D

Abstract:
A compound of formula (Ia): or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:D is an aryl or heteroaryl group attached through an unsaturated carbon atom; X is selected from the group CHâ€”R9, Nâ€”R10, O, S(O)n and a bond; n is 0, 1 or 2; R1 is selected from the group C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-8 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-4 alkoxy-C1-4 alkyl, â€”SO2â€”C1-10 alkyl, â€”SO2â€”R1a, and â€”SO2â€”R1b; R1 is substituted with 0-1 substituents selected from the group â€”CN, â€”S(O)nR14b, â€”COR13a, â€”CO2R13a, â€”NR15aCOR13a, â€”N(COR13a)2, â€”NR15aCONR13aR16a, â€”NR15aCO2R14b, â€”CONR13aR16a, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C3-8 cycloalkyl, wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from the group â€”Oâ€”, â€”S(O)nâ€”, â€”NR13aâ€”, â€”NCO2R14bâ€”, â€”NCOR14bâ€” and â€”NSO2R14bâ€”, and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b; R1 is also substituted with 0-3 substituents independently selected at each occurrence from the group R1a, R1b, R1c, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, â€”OR13a, â€”NR13aR16a, C1-4 alkoxy-C1-4 alkyl, and C3-8 cycloalkyl which is substituted with 0-1 R9 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by â€”Oâ€”; provided that R1 is other than a cyclohexyl-(CH2)2â€” group; R1a is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R1a being substituted with 0-1 â€”OR17 and 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, â€”CN, nitro, SH, â€”S(O)nR18, â€”COR17, â€”OC(O)R18, NR15aCOR17, â€”N(COR17)2, â€”NR15a CONR17aR19a, â€”NR15aCO2R18, â€”NR17aR19a, and â€”CONR17aR19a; R1b is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, â€”CN, nitro, â€”OR17, SH, â€”S(O)mR18, â€”COR17, â€”OC(O)R18, NR15aCOR17, â€”N(COR17)2, â€”NR15aCONR17aR19a, â€”NR15aCO2R18, â€”NR17aR19a, and â€”CONR17aR19a, and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15a, CO2R14b, COR14b and SO2R14b; R1c is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, â€”CN, nitro, â€”OR13a, SH, â€”S(O)nR14b, â€”COR13a, â€”OC(O)R14b, â€”NR15aCOR13a, â€”N(COR13a)2, â€”NR15aCONR13aR16a, â€”NR15aCO2R14b, â€”NR13aR16a, and â€”CONR13aR16a and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R13a, CO2R14b, COR14b and SO2R14b and wherein any sulfur atom is optionally monooxidized or dioxidized; provided that R1 is other than a â€”(CH2)1-4-aryl, â€”(CH2)1-4-heteroaryl, or â€”(CH2)1-4-heterocycle, wherein the aryl, heteroaryl, or heterocycle group is substituted or unsubstituted; R2 is selected from the group C1-4 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, and C2-4 alkynyl and is substituted with 0-3 substituents selected from the group â€”CN, hydroxy, halo and C1-4 alkoxy; alternatively R2, in the case where X is a bond, is selected from the group â€”CN, CF3 and C2F5; R8 is independently selected at each occurrence from the group H, Br, Cl, F, I, â€”CN, C1-4 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkyl sulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2amino; p1 R9 and R10 are independently selected at each occurrence from the group H, C1-4 alkyl, C3-6 cycloalkyl-C1-4 alkyl and C3-8 cycloalkyl; R13 is selected from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)â€”, heteroaryl and heteroaryl(C1-4 alkyl)â€”; R13a and R16a are independently selected at each occurrence from the group H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl; R14 is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl)â€”, heteroaryl and heteroaryl(C1-4 alkyl)â€” and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino; R14a is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino; R14b is selected from the group C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl; R15 is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino; R15a is independently selected at each occurrence from the group H, C1-4 alkyl, C3-7 cycloalkyl, and C3-6 cycloalkyl-C1-6 alkyl; R17 is selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, C1-4 haloalkyl, R14S(O)nâ€”C1-4 alkyl, and R17bR19bNâ€”C2-4 alkyl; R18 and R19 are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkoxy-C1-2 alkyl, and C1-4 haloalkyl; alternatively, in an NR17R19 moiety, R17 and R19 taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14; alternatively, in an NR17bR19b moiety, R17b and R19b taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from the group R13, CO2R14, COR14 and SO2R14; R17a and R19a are independently selected at each occurrence from the group H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl and C1-4 haloalkyl; aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkoxy-C1-4 alkoxy, â€”OR17, Br, Cl, F, I, C1-4 haloalkyl, â€”CN, â€”NO2, SH, â€”S(O)nR18, â€”COR17, â€”CO2R17, â€”OC(O)R18, â€”NR15COR17, â€”N(COR17)2, â€”NR15CONR17R19, â€”NR15CO2R18, â€”NR17R19, and â€”CONR17R19 and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C1-3 alkyl, C1-3 alkoxy, Br, Cl, F, I, â€”CN, dimethylamino, CF3, C2F5, OCF3, SO2Me and acetyl; heteroaryl is independently selected at each occurence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, â€”CN, nitro, â€”OR17, SH, â€”S(O)mR18, â€”COR17, â€”CO2R17, â€”OC(O)R18, â€”NR15COR17, â€”N(COR17)2, â€”NR15CONR17R19, â€”NR15CO2R18, â€”NR17R19, and â€”CONR17R19 and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R15, CO2R14a, COR14a and SO2R14a; and, provided that when D is imidazole or triazole, R1 is other than unsubstituted C1-6 linear or branched alkyl or C3-6 cycloalkyl.