[发明专利]用于治疗听力损伤和眩晕的β-咔啉无效
申请号: | 201080063025.6 | 申请日: | 2010-12-28 |
公开(公告)号: | CN102844029A | 公开(公告)日: | 2012-12-26 |
发明(设计)人: | H·罗美尔斯巴奇 | 申请(专利权)人: | 奥迪欧医药设备有限公司 |
主分类号: | A61K31/437 | 分类号: | A61K31/437;A61P27/16;A61P1/08;A61P25/00 |
代理公司: | 广州嘉权专利商标事务所有限公司 44205 | 代理人: | 张海文 |
地址: | 德国*** | 国省代码: | 德国;DE |
权利要求书: | 查看更多 | 说明书: | 查看更多 |
摘要: | 本发明涉及β-咔啉(优选9-烷基-β-咔啉(9-烷基-β-BC))、其制备及其在预防和治疗听力损伤、耳鸣、急性声创伤、眩晕及前庭障碍中的用途,以及包含这些β-咔啉的药物组合物。 | ||
搜索关键词: | 用于 治疗 听力 损伤 眩晕 咔啉 | ||
【主权项】:
1.通式(I)的化合物的用途,
其中,R1是下述基团中的一种:–R12、–CR4R5R6、-NR12R13、–CO-NH–R12、–CO–O–R12;R2–R6独立地代表以下基团:–R7、–R8、–R9、–R10、–R11、–H、–OH、–OR7、–OCH3、–OC2H5、–OC3H7、–O–cyclo-C3H5、–OCH(CH3)2、–OC(CH3)3、–OC4H9、-OPh、-OCH2-Ph、-OCPh3、–SH、–SCH3、–SC2H5、–SC3H7、–S–cyclo-C3H5、–SCH(CH3)2、–SC(CH3)3、-NO2、–F、–Cl、–Br、-I、-N3、–CN、–OCN、-NCO、–SCN、-NCS、–CHO、–COCH3、–COC2H5、–COC3H7、–CO–cyclo-C3H5、–COCH(CH3)2、–COC(CH3)3、–COOH、–COCN、–COOCH3、–COOC2H5、–COOC3H7、–COO–cyclo-C3H5、–COOCH(CH3)2、–COOC(CH3)3、–OOC-CH3、–OOC–C2H5、–OOC–C3H7、–OOC–cyclo-C3H5、–OOC–CH(CH3)2、–OOC–C(CH3)3、–CONH2、–CONHCH3、–CONHC2H5、–CONHC3H7、–CONH–cyclo-C3H5、–CONH[CH(CH3)2]、-CONH[C(CH3)3]、-CON(CH3)2、-CON(C2H5)2、-CON(C3H7)2、-CON(cyclo-C3H5)2、–CON[CH(CH3)2]2、–CON[C(CH3)3]2、-NHCOCH3、-NHCOC2H5、-NHCOC3H7、-NHCO-cyclo-C3H5、-NHCOCH(CH3)2、-NHCOC(CH3)3、-NHCO-OCH3、-NHCO-OC2H5、-NHCO–OC3H7、-NHCO–O–cyclo-C3H5、-NHCO–OCH(CH3)2、-NHCO–OC(CH3)3、-NH2、-NHCH3、-NHC2H5、-NHC3H7、-NH-cyclo-C3H5、-NHCH(CH3)2、-NHC(CH3)3、-N(CH3)2、-N(C2H5)2、-N(C3H7)2、-N(cyclo-C3H5)2、-N[CH(CH3)2]2、-N[C(CH3)3]2、–SOCH3、–SOC2H5、-SOC3H7、-SO-cyclo-C3H5、-SOCH(CH3)2、-SOC(CH3)3、-SO2CH3、-SO2C2H5、-SO2C3H7、-SO2-cyclo-C3H5、-SO2CH(CH3)2、-SO2C(CH3)3、-SO3H、-SO3CH3、-SO3C2H5、-SO3C3H7、-SO3-cyclo-C3H5、-SO3CH(CH3)2、-SO3C(CH3)3、-OCF3、-OC2F5、-O-COOCH3、-O-COOC2H5、-O-COOC3H7、-O-COO-cyclo-C3H5、-O-COOCH(CH3)2、-O-COOC(CH3)3、-NH-CO-NH2、-NH-CO-NHCH3、-NH-CO-NHC2H5、-NH-CO-NHC3H7、-NH-CO-NH-cyclo-C3H5、-NH–CO-NH[CH(CH3)2]、-NH–CO-NH[C(CH3)3]、-NH–CO-N(CH3)2、-NH–CO-N(C2H5)2、-NH–CO-N(C3H7)2、-NH-CO-N(cyclo-C3H5)2、-NH–CO-N[CH(CH3)2]2、-NH-CO-N[C(CH3)3]2、-NH-CS-NH2、-NH-CS-NHCH3、-NH-CS-NHC2H5、-NH–CS–NHC3H7、-NH–CS-NH–cyclo-C3H5、-NH–CS-NH[CH(CH3)2]、-NH–CS-NH[C(CH3)3]、–NH–CS-N(CH3)2、-NH–CS-N(C2H5)2、-NH–CS-N(C3H7)2、-NH–CS-N(cyclo-C3H5)2、-NH–CS-N[CH(CH3)2]2、-NH–CS-N[C(CH3)3]2、-NH–C(=NH)-NH2、-NH–C(=NH)-NHCH3、-NH–C(=NH)-NHC2H5、-NH–C(=NH)-NHC3H7、–OC6H4-OCH3、-NH–C(=NH)-NH–cyclo-C3H5、-NH–C(=NH)-NH[CH(CH3)2]、-CF2Cl、-NH–C(=NH)-NH[C(CH3)3]、-NH–C(=NH)-N(CH3)2、-NH–C(=NH)-N(C2H5)2、-NH–C(=NH)-N(C3H7)2、-NH–C(=NH)-N(cyclo-C3H5)2、–OC6H4-CH3、-NH–C(=NH)-N[CH(CH3)2]2、-NH–C(=NH)-N[C(CH3)3]2、–O–CO-NH2、–O–CO-NHCH3、–O–CO-NHC2H5、–O–CO-NHC3H7、–O–CO-NH–cyclo-C3H5、–O–CO-NH[CH(CH3)2]、–O–CO-NH[C(CH3)3]、–O–CO-N(CH3)2、–O–CO-N(C2H5)2、–O–CO-N(C3H7)2、–O–CO-N(cyclo-C3H5)2、–O–CO-N[CH(CH3)2]2、–O–CO-N[C(CH3)3]2、–O–CO–OCH3、–O–CO–OC2H5、–O–CO–OC3H7、–O–CO–O–cyclo-C3H5、–O–CO–OCH(CH3)2、–O–CO–OC(CH3)3、–CH2–COOH、–CH2–COOCH3、–CH2–COOC2H5、–CH2–COC3H7、–CH2–CO–cyclo-C3H5、–CH2–COCH(CH3)2、–CH2–COC(CH3)3。R7–R13独立地代表以下基团:-CH2F、-CHF2、-CF3、-CH2Cl、-CH2Br、-CH2I、-CH2-CH2F、-CH2-CHF2、-CH2-CF3、-CH2-CH2Cl、-CH2-CH2Br、-CH2-CH2I、cyclo-C3H5、cyclo-C4H7、cyclo-C5H9、cyclo-C6H11、cyclo-C7H13、cyclo-C8H15、-Ph、-CH2-Ph、-CPh3、-CH3、-C2H5、-C3H7、-CH(CH3)2、-C4H9、-CH2-CH(CH3)2、-CH(CH3)-C2H5、-C(CH3)3、-C5H11、-CH(CH3)–C3H7、–CH2–CH(CH3)–C2H5、-CH(CH3)-CH(CH3)2、-C(CH3)2-C2H5、-CH2-C(CH3)3、-CH(C2H5)2、-C2H4-CH(CH3)2、-C6H13、–C3H6–CH(CH3)2、–C2H4–CH(CH3)–C2H5、–CH(CH3)–C4H9、–CH2–CH(CH3)–C3H7、-CH(CH3)-CH2-CH(CH3)2、-CH(CH3)-CH(CH3)-C2H5、-CH2-CH(CH3)-CH(CH3)2、–CH2–C(CH3)2–C2H5、–C(CH3)2–C3H7、–C(CH3)2–CH(CH3)2、–C2H4–C(CH3)3、-CH(CH3)-C(CH3)3、-CH=CH2、-CH2-CH=CH2、-C(CH3)=CH2、-CH=CH-CH3、–C2H4–CH=CH2、-C7H15、-C8H17、–CH2–CH=CH–CH3、–CH=CH–C2H5、–CH2–C(CH3)=CH2、-CH(CH3)-CH=CH、-CH=C(CH3)2、-C(CH3)=CH-CH3、-CH=CH-CH=CH2、-C3H6-CH=CH2、-C2H4-CH=CH-CH3、-CH2-CH=CH-C2H5、-CH=CH-C3H7、-CH2-CH=CH-CH=CH2、-CH=CH-CH=CH-CH3、-CH=CH-CH2-CH=CH2、-C(CH3)=CH-CH=CH2、-CH=C(CH3)-CH=CH2、-CH=CH-C(CH3)=CH2、-C2H4-C(CH3)=CH2、-CH2-CH(CH3)-CH=CH2、-CH(CH3)-CH2-CH=CH2、-CH2-CH=C(CH3)2、-CH2-C(CH3)=CH-CH3、-CH(CH3)-CH=CH-CH3、-CH=CH-CH(CH3)2、-CH=C(CH3)-C2H5、-C(CH3)=CH-C2H5、-C(CH3)=C(CH3)2、-C(CH3)2-CH=CH2、-CH(CH3)-C(CH3)=CH2、-C(CH3)=CH-CH=CH2、-CH=C(CH3)-CH=CH2、-CH=CH-C(CH3)=CH2、-C4H8-CH=CH2、–C3H6–CH=CH–CH3、–C2H4–CH=CH–C2H5、–CH2–CH=CH–C3H7、–CH=CH–C4H9、–C3H6–C(CH3)=CH2、-CH2-CH2-CH2-OCH3、–C2H4–CH(CH3)–CH=CH2、–CH2–CH(CH3)–CH2–CH=CH2、-CH2NH2、–CH(CH3)–C2H4–CH=CH2、–C2H4–CH=C(CH3)2、–C2H4–C(CH3)=CH-CH3、–CH2–CH(CH3)–CH=CH–CH3、–CH(CH3)–CH2–CH=CH–CH3、-CH2OH、-CH2SH、–CH2-CH=CH–CH(CH3)2、–CH2–CH=C(CH3)–C2H5、-CH2-CH2-CH2NH2、–CH2–C(CH3)=CH–C2H5、–CH(CH3)–CH=CH–C2H5、-CH2-CH2NH2、–CH=CH–CH2–CH(CH3)2、–CH=CH–CH(CH3)–C2H5、–CH=C(CH3)–C3H7、–C(CH3)=CH–C3H7、–CH2–CH(CH3)–C(CH3)=CH2、-CH2-CH2SH、–CH(CH3)–CH2–C(CH3)=CH2、–CH(CH3)–CH(CH3)-CH=CH2、-CH2-CH2-CH2OH、–CH2–C(CH3)2–CH=CH2、–C(CH3)2–CH2–CH=CH2、–CH2–C(CH3)=C(CH3)2、–CH(CH3)–CH=C(CH3)2、–C(CH3)2–CH=CH-CH3、-CH2-CH2-CH2SH、–CH(CH3)–C(CH3)=CH-CH3、–CH=C(CH3)–CH(CH3)2、–C(CH3)=CH–CH(CH3)2、–C(CH3)=C(CH3)–C2H5、–CH=CH–C(CH3)3、–C(CH3)2–C(CH3)=CH2、–CH(C2H5)–C(CH3)=CH2、–C(CH3)(C2H5)–CH=CH2、–CH(CH3)–C(C2H5)=CH2、–CH2–C(C3H7)=CH2、–CH2–C(C2H5)=CH–CH3、–CH(C2H5)–CH=CH-CH3、–C(C4H9)=CH2、–C(C3H7)=CH–CH3、–C(C2H5)=CH-C2H5、–C(C2H5)=C(CH3)2、–C[C(CH3)3]=CH2、–C[CH(CH3)(C2H5)]=CH2、–C[CH2–CH(CH3)2]=CH2、–C2H4–CH=CH–CH=CH2、-C6H4-OCH3、–CH2–CH=CH–CH2–CH=CH2、–CH=CH–C2H4–CH=CH2、-C6H4-OH、–CH2–CH=CH–CH=CH–CH3、–CH=CH–CH2–CH=CH–CH3、-CH2-CH2-OCH3、–CH=CH–CH=CH–C2H5、-CH2-CH=CH-C(CH3)=CH2、-CH2-CH2OH、-CH2-CH=C(CH3)-CH=CH2、–CH2–C(CH3)=CH–CH=CH2、-CH2-OCH3、–CH(CH3)–CH=CH–CH=CH2、-CH=CH-CH2-C(CH3)=CH2、-CH=CH-CH(CH3)-CH=CH2、-CH=C(CH3)-CH2-CH=CH2、–C(CH3)=CH–CH2-CH=CH2、–CH=CH–CH=C(CH3)2、-CH2-C6H4-OCH3、-CH=CH-C(CH3)=CH-CH3、-CH=C(CH3)-CH=CH-CH3、-CH2-C6H4-OH、–C(CH3)=CH-CH=CH-CH3、–CH=C(CH3)–C(CH3)=CH2、–C(CH3)=CH–C(CH3)=CH2、-C(CH3)=C(CH3)-CH=CH2、-CH=CH-CH=CH-CH=CH2、-C≡CH、-C≡C-CH3、-CH2-C≡CH、-C2H4-C≡CH、-CH2-C≡C-CH3、-C≡C-C2H5、-C3H6-C≡CH、-C2H4-C≡C-CH3、-CH2-C≡C-C2H5、-C≡C-C3H7、-CH(CH3)-C≡CH 、-CH2-CH(CH3)-C≡CH 、-CH(CH3)-CH2-C≡CH 、-CH(CH3)-C≡C-CH3、-C4H8-C≡CH、-C3H6-C≡C-CH3、-C2H4-C≡C-C2H5、-CH2-C≡C-C3H7、-C≡C-C4H9、-C≡C-C(CH3)3、-C2H4-CH(CH3)-C≡CH、-CH2-CH(CH3)-CH2-C≡CH、-CH2-C≡C-CH(CH3)2、-CH(CH3)-C2H4-C≡CH、-CH2-CH(CH3)-C≡C-CH3、-CH(CH3)-CH2-C≡C-CH3、-CH(CH3)-C≡C-C2H5、-C≡C-CH(CH3)-C2H5、-C≡C-CH2-CH(CH3)2、-CH(C2H5)-C≡C-CH3、-C(CH3)2-C≡C-CH3、–CH(C2H5)-CH2–C≡CH、–CH2–CH(C2H5)-C≡CH、–C(CH3)2–CH2–C≡CH、–CH2–C(CH3)2–C≡CH、–CH(CH3)–CH(CH3)-C≡CH、–CH(C3H7)-C≡CH、–C(CH3)(C2H5)–C≡CH、–C≡C–C≡CH、–CH2–C≡C–C≡CH、–C≡C–C≡C–CH3、–CH(C≡CH)2、–C2H4–C≡C–C≡CH、–CH2–C≡C–CH2–C≡CH、–C≡C–C2H4–C≡CH、–CH2–C≡C–C≡C–CH3、–C≡C–CH2–C≡C–CH3、–C≡C–C≡C–C2H5、–C≡C–CH(CH3)-C≡CH、–CH(CH3)–C≡C–C≡CH、–CH(C≡CH)–CH2–C≡CH、–C(C≡CH)2–CH3、–CH2–CH(C≡CH)2、–CH(C≡CH)–C≡C–CH3、–C14H29、–CH2–CH2-N(CH3)2;以及药学上可接受的盐、溶剂化物、水合物、络合物、对映异构体、非对映异构体以及前述化合物的外消旋体,用于制备预防和治疗听力损伤、眩晕和前庭障碍的药物组合物。
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