发明名称 Substituted pyrrolo[2,3-h][1,6]naphthyridines and compositions thereof as JAK inhibitors
摘要 Novel tricyclic pyrimidine compounds and tricyclic pyridine compounds having JAK inhibitory activities are provided. A tricyclic heterocyclic compound represented by the formula (Ia): wherein the rings Aa and Ba, Xa, Ya, R1a, R2a, R3a, L1a L2a, L3a and na are as defined in the description.;
申请公布号 US9216999(B2) 申请公布日期 2015.12.22
申请号 US201214238507 申请日期 2012.08.10
申请人 Nissan Chemical Industries, Ltd. 发明人 Hayashi Keishi;Watanabe Tsuneo;Toyama Koji;Kamon Junji;Minami Masataka;Uni Miyuki;Nasu Mariko
分类号 A61K31/4375;C07D471/14;C07D513/14;C07D487/14;C07D498/14 主分类号 A61K31/4375
代理机构 Oblon, McClelland, Maier & Neustadt, L.L.P. 代理人 Oblon, McClelland, Maier & Neustadt, L.L.P.
主权项 1. A compound represented by the formula (Ib):wherein: the ring Ab is represented by the formula (IIb): T1b is C(═O); U1b is CH; W1b is CH; Xb is CH; Yb is CH; R1b is a hydrogen atom, a halogen atom, a C1-6 alkyl group or a C1-6 haloalkyl group; the ring Bb is a C3-11 cycloalkane, a C3-11 cycloalkene, a 3 to 11-membered non-aromatic heterocycle, a C6-14 aromatic carbocycle or a 5 to 10-membered aromatic heterocycle; L1b is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group (the C1-6 alkylene group, the C2-6 alkenylene group and the C2-6 alkynylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups); L2b is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group (the C1-6 alkylene group, the C2-6 alkenylene group and the C2-6 alkynylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups); L3b is a single bond or represented by any of the following formulae (Vb-1) to (Vb-20): E1b is an oxygen atom, a sulfur atom or NR18b; when L3b is a single bond, R2b is a hydrogen atom, a halogen atom, a C3-11 cycloalkyl group, a 3 to 14-membered non-aromatic heterocyclyl group, a C6-14 aryl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C3-11 cycloalkyl group, the 3 to 14-membered non-aromatic heterocyclyl group, the C6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from a substituent set V4b and a substituent set V9b); when L3b is not a single bond, R2b is a hydrogen atom, a C1-6 alkyl group, a C2-6 alkenyl group (the C1-6 alkyl group and the C2-6 alkenyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from a substituent set V6b and a substituent set V9b), a C3-11 cycloalkyl group, a 3 to 14-membered non-aromatic heterocyclyl group, a C6-14 aryl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C3-11 cycloalkyl group, the 3 to 14-membered non-aromatic heterocyclyl group, the C6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V4b and substituent set V9b); nb is 0, 1 or 2; R3b is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C1-6 alkyl group, a C1-6 haloalkyl group, a C3-11 cycloalkyl group, a C2-6 alkenyl group, a C2-6 haloalkenyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C1-6 alkylthio group, a C1-6 haloalkylthio group, a C1-6 alkylcarbonyl group, a C1-6 haloalkylcarbonyl group, a C1-6 alkylsulfonyl group, a C1-6 haloalkylsulfonyl group, a C1-6 alkoxycarbonyl group, a mono-C1-6 alkylamino group, a di-C1-6 alkylamino group, a mono-C1-6 alkylaminocarbonyl group, a di-C1-6 alkylaminocarbonyl group or a C1-6 alkylcarbonylamino group (when nb is 2, R3b′s may be identical or different); each of R12b, R13b and R14b is independently a hydrogen atom, a C1-6 alkyl group or a C1-6 haloalkyl group (the C1-6 alkyl group and the C1-6 haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from a substituent set V3b, a substituent set V8b and a substituent set V9b); R18b is a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C1-6 alkyl group or a C1-6 alkoxy group; a substituent set V1b consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C1-6 alkyl groups, C1-6 haloalkyl groups, C3-11 cycloalkyl groups, C2-6 alkenyl groups, C2-6 haloalkenyl groups, C1-6 alkoxy groups, C1-6 haloalkoxy groups, C1-6 alkylthio groups, C1-6 haloalkylthio groups, C1-6 alkylcarbonyl groups, C1-6 haloalkylcarbonyl groups, C1-6 alkylsulfonyl groups, C1-6 haloalkylsulfonyl groups, C1-6 alkoxycarbonyl groups, 3 to 11 -membered non-aromatic heterocyclyl groups, mono-C1-6 alkylamino groups, di-C1-6 alkylamino groups, mono-C1-6 alkylaminocarbonyl groups, di-C1-6 alkylaminocarbonyl groups and C1-6 alkylcarbonylamino groups; a substituent set V2b consists of the groups in the substituent set V1b, and C6-14 aryl groups and 5 to 10-membered aromatic heterocyclyl groups (the C6-14 aryl groups and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V 1b); the substituent set V3b consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C1-6 alkoxy groups, C1-6 haloalkoxy groups, C1-6 alkylthio groups, C1-6 haloalkylthio groups, C1-6 alkylcarbonyl groups, C1-6 haloalkylcarbonyl groups, C1-6 alkylsulfonyl groups, C1-6 haloalkylsulfonyl groups, C1-6 alkoxycarbonyl groups, mono-C1-6 alkylamino groups, di-C1-6 alkylamino groups, mono-C1-6 alkylaminocarbonyl groups, di-C1-6 alkylaminocarbonyl groups, C1-6 alkylcarbonylamino groups, C3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C6-14 aryl groups and 5 to 10-membered aromatic heterocyclyl groups (the C3-11 cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C6-14 aryl groups and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V1b); the substituent set V4b consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C1-6 alkyl groups, C2-6 alkenyl groups, C1-6 alkoxy groups, C1-6 alkylthio groups, C1-6 alkylcarbonyl groups, C1-6 alkylsulfonyl groups, C1-6 alkoxycarbonyl groups, mono-C1-6 alkylamino groups, di-C1-6 alkylamino groups, mono-C1-6 alkylaminocarbonyl groups, di-C1-6 alkylaminocarbonyl groups, C1-6 alkylcarbonylamino groups (the C1-6 alkyl groups, the C2-6 alkenyl groups, the C1-6 alkoxy groups, the C1-6 alkylthio groups, the C1-6 alkylcarbonyl groups, the C1-6 alkylsulfonyl groups, the C1-6 alkoxycarbonyl groups, the mono-C1-6 alkylamino groups, the di-C1-6 alkylamino groups, the mono-C1-6 alkylaminocarbonyl groups, the di-C1-6 alkylaminocarbonyl groups and the C1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V3b), C3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C6-14 aryl groups and 5 to 10-membered aromatic heterocyclyl groups (the C3-11 cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C6-14 aryl groups and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V1b); a substituent set V5b consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C1-6 alkoxy groups, C1-6 alkylthio groups, C1-6 alkylcarbonyl groups, C1-6 alkylsulfonyl groups, C1-6 alkoxycarbonyl groups, mono-C1-6 alkylamino groups, di-C1-6 alkylamino groups, mono-C1-6 alkylaminocarbonyl groups, di-C1-6 alkylaminocarbonyl groups, C1-6 alkylcarbonylamino groups, C3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C6-14 aryl groups and 5 to 10-membered aromatic heterocyclyl groups (the C1-6 alkoxy groups, the C1-6 alkylthio groups, the C1-6 alkylcarbonyl groups, the C1-6 alkylsulfonyl groups, the C1-6 alkoxycarbonyl groups, the mono-C1-6 alkylamino groups, the di-C1-6 alkylamino groups, the mono-C1-6 alkylaminocarbonyl groups, the di-C1-6 alkylaminocarbonyl groups, the C1-6 alkylcarbonylamino groups, the C3-11 cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C6-14 aryl groups and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V3b); the substituent set V6b consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C1-6 alkoxy groups, C1-6 alkylthio groups, C1-6 alkylcarbonyl groups, C1-6 alkylsulfonyl groups, C1-6 alkoxycarbonyl groups, mono-C1-6 alkylamino groups, di-C1-6 alkylamino groups, mono-C1-6 alkylaminocarbonyl groups, di-C1-6 alkylaminocarbonyl groups, C1-6 alkylcarbonylamino groups (the C1-6 alkoxy groups, the C1-6 alkylthio groups, the C1-6 alkylcarbonyl groups, the C1-6 alkylsulfonyl groups, the C1-6 alkoxycarbonyl groups, the mono-C1-6 alkylamino groups, the di-C1-6 alkylamino groups, the mono-C1-6 alkylaminocarbonyl groups, the di-C1-6 alkylaminocarbonyl groups and the C1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V3b), C3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C6-14 aryl groups, 5 to 10-membered aromatic heterocyclyl groups, 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the C3-11 cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C6-14 aryl groups, the 5 to 10-membered aromatic heterocyclyl groups, the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V4b and the substituent set V9b); the substituent set V8b consists of 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V2b); and the substituent set V9b consists of, mono-C1-6 alkylaminosulfonyl groups, di-C1-6 alkylaminosulfonyl groups, C1-6 alkylsulfonylamino groups (the mono-C1-6 alkylaminosulfonyl groups, di-C1-6 alkylaminosulfonyl groups and C1-6 alkylsulfonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V3b), C3-6 cycloalkoxy groups, C3-6 cycloalkylamino groups, C3-6 cycloalkylthio groups, C3-6 cycloalkylcarbonyl groups and C3-6 cycloalkylsulfonyl groups (the C3-6 cycloalkoxy groups, the C3-6 cycloalkylamino groups, the C3-6 cycloalkylthio groups, the C3-6 cycloalkylcarbonyl groups and the C3-6 cycloalkylsulfonyl groups unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V2b), a tautomer or a pharmaceutically acceptable salt of the compound.
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