发明名称 SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS
摘要 The invention is concerned with the compounds of formula I or II:;;and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
申请公布号 US2016221945(A1) 申请公布日期 2016.08.04
申请号 US201615095467 申请日期 2016.04.11
申请人 Genentech, Inc. 发明人 CHEN Huifen;CHU Yanyan;DO Steven;ESTRADA Anthony;HU Baihua;KOLESNIKOV Aleksandr;LIN Xingyu;LYSSIKATOS Joseph P.;SHORE Daniel;VERMA Vishal;WANG Lan;WU Guosheng;YUEN Po-wai
分类号 C07D207/48;C07D403/12;C07D403/14;C07D417/12;C07D405/14;C07D491/048;C07D451/02;C07D401/14;C07D401/12 主分类号 C07D207/48
代理机构 代理人
主权项 1. A compound of formula II:wherein: (1) A isB is B1 and R5 is R5a; or (2) A isB is B2 and R5 is R5b; or (3) A isB is B3 and R5 is R5a; or (4) A isB is B4 and R5 is R5a; or (5) A isB is B1 and R5 is R5a; or (6) A isB is B5 and R5 is R5a; or (7) A isB is B3 and R5 is R5a; B is B1, B2, B3, B4, or B5; B1 is a 5-membered heteroaryl comprising 2 or 3 nitrogen atoms in the ring or a 6-membered heteroaryl, wherein any 5-membered heteroaryl or 6-membered heteroaryl of B′ is optionally substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, —O(C1-C6)alkyl and (C3-C7)cycloalkyl; B2 is a pyridinyl, wherein any pyridinyl of B2 is optionally substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, —O(C1-C6)alkyl, —O(C1-C6)alkyl-O(C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl, —CN, and 6-membered heteroaryl, wherein any 6-membered heteroaryl is optionally substituted with one or more (C1-C6)alkyl or (C1-C6)haloalkyl; B3 is a 5-membered heteroaryl comprising 2 or 3 nitrogen atoms in the ring or a 6-membered heteroaryl comprising 2 nitrogen atoms in the ring, wherein any 5-membered heteroaryl or 6-membered heteroaryl of B3 is optionally substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, —O(C1-C6)alkyl, (C3-C7)cycloalkyl, —CN, and NR62, and wherein when B3 is pyrimidinyl which is attached to the remainder of Formula II at the 4 and 6 positions of the pyrimidinyl, then R5a is not pyrrolidinyl or substituted pyrrolidinyl; B4 is a 5-membered heteroaryl, 6-membered heteroaryl, or phenyl, wherein any 5-membered heteroaryl, 6-membered heteroaryl, or phenyl of B4 is optionally substituted with one or more groups independently selected from halogen, —CN, (C1-C6)alkyl, —O(C1-C6)alkyl and (C3-C7)cycloalkyl; B5 is a phenyl optionally substituted with one or more groups independently selected from —CN, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, —O(C1-C6)alkyl, and —O(C1-C6)haloalkyl; R1 is a phenyl, 5-membered heteroaryl or 6-membered heteroaryl, wherein any phenyl, 5-membered heteroaryl or 6-membered heteroaryl of R1 is optionally substituted with one or more groups independently selected from halogen, —CN, (C1-C6)alkyl and (C1-C6)haloalkyl; R2 is halogen, (C1-C6)alkyl or CN, wherein any (C1-C6)alkyl of R2 is optionally substituted with one or more groups independently selected from halogen, —OH and —O(C1-C6)alkyl; each R3a is independently selected from H, halogen and (C1-C6)alkyl; one R3b group is halogen, —CN, or (C1-C6)alkyl and the remaining R3b groups are independently selected from H, (C1-C6)alkyl and (C1-C6)haloalkyl; one R3b′ group is halogen, (C1-C6)alkyl, —CN, or (C1-C6)haloalkyl and the remaining R3b′ groups are independently selected from H, (C1-C6)alkyl and (C1-C6)haloalkyl; two R3c groups attached to different non-adjacent carbon atoms or adjacent carbon atoms are combined to form a (C1-C4)alkyl linker or a (C1-C2)alkyl-O—(C1-C2)alkyl linker, wherein the (C1-C4)alkyl linker or (C1-C2)alkyl-O—(C1-C2)alkyl linker is optionally substituted with one or more groups independently selected from halogen and (C1-C6)alkyl, and the remaining R3c groups are independently selected from H, halogen and (C1-C6)alkyl; each R3d group is independently selected from H, halogen, (C1-C6)alkyl, and —CN, wherein any (C1-C6)alkyl of R3d is optionally substituted with one or more groups independently selected from halogen, —OH and —O(C1-C6)alkyl; one R3e group is halogen, —CN or (C1-C6)alkyl and the remaining R3e groups are independently selected from H, (C1-C6)alkyl and (C1-C6)haloalkyl; two R3f groups attached to the same carbon atom are combined to form a (C2-C4)alkyl linker, wherein the (C2-C4)alkyl linker is optionally substituted with one or more groups independently selected from halogen and (C1-C6)alkyl, and the remaining R3f groups are independently selected from H, halogen and (C1-C6)alkyl; R4 is H, (C1-C6)alkyl or (C1-C6)haloalkyl; R5 is R5a or R5b; R5a is a phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 4, 5, 6 or 7-membered heterocycle or (C3-C8)cycloalkyl, wherein any phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 4, 5, 6 or 7-membered heterocycle or (C3-C8)cycloalkyl of R5a is optionally substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, —CN, (C3-C7)cycloalkyl, —O(C1-C6)alkyl, —O(C1-C6)alkyl-O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —S(C1-C6)alkyl, —S(C1-C6)haloalkyl, oxo and —O—(C1-C2)alkyl-O— optionally substituted with one or more halogen, which —O—(C1-C2)alkyl-O— group is bonded to two adjacent carbon atoms of any phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 4, 5, 6 or 7-membered heterocycle or (C3-C8)cycloalkyl of R5a; R5b is a phenyl, 5-membered heteroaryl, 6-membered heteroaryl or 4, 5, 6, 7 or 8-membered heterocycle, wherein any phenyl, 5-membered heteroaryl, 6-membered heteroaryl or 4, 6, 7 or 8-membered heterocycle of R5b is optionally substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, —CN, (C3-C7)cycloalkyl optionally substituted with one or more halogen, —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —OH, —S(C1-C6)alkyl, —S(C1-C6)haloalkyl, and NR62, and wherein any 5-membered heterocycle of R5b is substituted with one or more groups independently selected from halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, —CN, (C3-C7)cycloalkyl, —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —S(C1-C6)alkyl and —S(C1-C6)haloalkyl; and each R6 is independently H or (C1-C6)alkyl; or a salt thereof.
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