发明名称 PICOLINAMIDE DERIVATIVES AS TTX-S BLOCKERS
摘要 The present invention relates to picolinamide derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.
申请公布号 US2014296237(A1) 申请公布日期 2014.10.02
申请号 US201414302572 申请日期 2014.06.12
申请人 RaQualia Pharma Inc. 发明人 NOGUCHI Hirohide;INOUE Tadashi;MORITA Mikio;ARANO Yoshimasa
分类号 C07D401/12;C07D413/14;C07D401/14 主分类号 C07D401/12
代理机构 代理人
主权项 1. A compound of formula (I): wherein: R1 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxy, (4) —Op—C1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R5, (5) —Op—C3-8 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R5, (6) C2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R5, (7) —(C═O)—NR6R7, (8) —NR6R7, (9) —S(O)2—NR6R7, (10) —NR6—S(O)2R7, (11) —S(O)r—R8, where r is 0, 1 or 2 and where R8 is selected from the definitions of R6 and R7, (12) —CO2H, and (13) —CN; where p is 0 or 1 (wherein if p is 0, a chemical bond is present in the place of Op); n is 1, 2, or 3; when n is two or more than two, R1 may be the same or different;R2 is selected from the group consisting of: (1) hydrogen, (2) C1-6 alkyl, which is unsubstituted or substituted with one or more substituents selected from R5, (3) C3-8 cycloalkyl which is unsubstituted or substituted with one or more substituents selected from R5, (4) phenyl, which is unsubstituted or substituted with one or more substituents selected from R5, and (5) heterocycle, which is unsubstituted or substituted with one or more substituents selected from R5; R3 is selected from the group consisting of: (1) —C0-3 alkyl-Op—C0-3 alkyl-cycloalkyl which is unsubstituted or substituted with one or more substituents selected from R5, (2) —C0-3 alkyl-Op—C0-3 alkyl-phenyl, which is unsubstituted or substituted with one or more substituents selected from R5, and (3) —C0-3 alkyl-Op—C0-3 alkyl-heterocycle, which is unsubstituted or substituted with one or more substituents selected from R5; where p is 0 or 1, (wherein if p is 0, a chemical bond is present in the place of Op); R4 is selected from the group consisting of: (1) hydrogen, (2) C1-6 alkyl, and (3) hydroxy; m is 1, 2, or 3; when m is two or more than two, R4 may be the same or different; R4 may form the bond with any carbon atom on the cyclic amine ring;k is 1;Y is a carbon atom;R5 is selected from the group consisting of: (1) halogen, (2) hydroxy, (3) —(C═O)q—Or—C1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R9, (4) —Op—(C1-3)perfluoroalkyl, (5) —(C═O)q—Or—C3-8 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R9, (6) —(C═O)q—Or—C2-4 alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R9, (7) —(C═O)q—Or-phenyl or —(C═O)q—Ornapthyl, where the phenyl or napthyl is unsubstituted or substituted with one or more substituents selected from R9, (8) —(C═O)q—Orheterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R9, (9) —(C═O)—NR6R7, (10) —NR6R7, (11) —S(O)2—NR6R7, (12) —S(O)r—R8, where t is 0, 1 or 2, (13) —CO2H, (14) —CN, and (15) —NO2; where p is 0 or 1, (wherein if p is 0, a chemical bond is present in the place of Op) and where q is 0 or 1 and r is 0 or 1 (wherein if q is 0 or r is 0, a bond is present in the place of (C═O)q or Or, and wherein if q is 0 and r is 0, a single bond is present in the place of (C═O)q—Or); R6 and R7 are independently selected from the group consisting of: (1) hydrogen, (2) C1-6 alkyl, which is unsubstituted or substituted with R5, (3) C3-6 alkenyl, which is unsubstituted or substituted with R5, (4) C3-8 cycloalkyl which is unsubstituted or substituted with R5, (5) phenyl, which is unsubstituted or substituted with R5, and (6) heterocycle, which is unsubstituted or substituted with R5, or R6 and R7 taken together with the nitrogen atom to which they are attached form a 3 to 8 membered ring, where the ring may contain one to four heteroatom independently selected from the group consisting of nitrogen, oxygen, and sulfur; where the ring may be saturated or partially saturated or unsaturated; which is unsubstituted or substituted one or more substituents selected from R5; R8 is selected from the definitions of R6 and R7;R9 is selected from the group consisting of: (1) hydroxy, (2) halogen, (3) C1-6 alkyl, (4) —C3-8 cycloalkyl, (5) —O—C1-6 alkyl, (6) —O(C═O)—C1-6 alkyl, (7) —NH—C1-6 alkyl, (8) phenyl, (9) heterocycle, (10) —CO2H, and (11) —CN; or a pharmaceutically acceptable salt thereof.
地址 Aichi JP