公开(公告)号：US5763474A

公开(公告)日：1998-06-09

申请号：US889164

申请日：1997-07-07

申请人： David R. Herbst ,  Madelene M. Antane ,  Geraldine R. McFarlane ,  Eric G. Gundersen ,  Bradford H. Hirth ,  Dominick A. Quagliato ,  Russell F. Graceffa ,  John A. Butera

发明人： David R. Herbst ,  Madelene M. Antane ,  Geraldine R. McFarlane ,  Eric G. Gundersen ,  Bradford H. Hirth ,  Dominick A. Quagliato ,  Russell F. Graceffa ,  John A. Butera

IPC分类号： C07C225/20 ,  C07C233/41 ,  C07C255/58 ,  C07C271/24 ,  A61K31/135 ,  A61K31/165 ,  C07C235/82

CPC分类号： C07C225/20 ,  C07C233/41 ,  C07C255/58 ,  C07C271/24 ,  C07C2101/04 ,  C07C2101/08

摘要： The compounds of the formula: ##STR1## wherein R.sub.1 is straight chain alkyl, branched chain alkyl cycloalkyl, hydroxyalkyl, fluoroalkyl or polyfluoroalkyl; R.sub.2 and R.sub.3 are, independently, hydrogen or an acyl substituent selected from the group consisting of formyl, alkanoyl, alkenoyl, alkoxycarbonyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is a substituted phenyl group of the following formula: ##STR2## wherein R.sub.4 and R.sub.5 are, independently, cyano, nitro, amino, alkyl, perfluoroalkyl, fluoroalkyl, alkoxy, perfluoroalkoxy, fluoroalkoxy, amino, alkylamino, dialkylamino, sulfamyl, alkylsulfonamido, arylsulfonamido, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarboxamido, arylcarboxamido, alkylsulfonyl, perfluoroalkylsulfonyl, arylsulfonyl, chloro, bromo, fluoro, iodo, 1-imidazolyl, carboxyl or hydrogen, with the proviso that R.sub.4 and R.sub.5 cannot both be hydrogen; or a pharmaceutically acceptable salt thereof, relaxes smooth muscles.

摘要翻译： 下式的化合物：其中R 1是直链烷基，支链烷基环烷基，羟基烷基，氟烷基或多氟烷基; R2和R3独立地为氢或选自甲酰基，烷酰基，烯酰基，烷氧基羰基，烷基磺酰基，芳酰基，芳基烯酰基，芳基磺酰基，芳基烷酰基或芳基烷基磺酰基的酰基取代基。 A是下式的取代苯基：其中R 4和R 5独立地是氰基，硝基，氨基，烷基，全氟烷基，氟烷基，烷氧基，全氟烷氧基，氟烷氧基，氨基，烷基氨基，二烷基氨基，氨基磺酰基，烷基亚磺酰氨基， 芳基亚磺酰氨基，氨基甲酰基，烷基氨基甲酰基，二烷基氨基甲酰基，烷基酰胺基，芳基羧酰氨基，烷基磺酰基，全氟烷基磺酰基，芳基磺酰基，氯，溴，氟，碘，1-咪唑基，羧基或氢，条件是R4和R5不能都是氢; 或其药学上可接受的盐，使平滑肌松弛。

公开(公告)号：US5780505A

公开(公告)日：1998-07-14

申请号：US889166

申请日：1997-07-07

申请人： Madelene M. Antane ,  David R. Herbst ,  Geraldine R. McFarlane ,  Eric G. Gundersen ,  Bradford H. Hirth ,  Dominick A. Quagliato ,  Russell F. Graceffa ,  John A. Butera

发明人： Madelene M. Antane ,  David R. Herbst ,  Geraldine R. McFarlane ,  Eric G. Gundersen ,  Bradford H. Hirth ,  Dominick A. Quagliato ,  Russell F. Graceffa ,  John A. Butera

IPC分类号： C07C225/20 ,  C07C233/41 ,  C07C255/58 ,  C07C271/24 ,  A61K31/275

CPC分类号： C07C255/58 ,  C07C225/20 ,  C07C233/41 ,  C07C271/24 ,  C07C2101/04 ,  C07C2101/08

摘要： The compounds of the formula: ##STR1## wherein R.sub.1 is straight chain alkyl, branched chain alkyl, cycloalkyl, hydroxyalkyl, fluoroalkyl or polyfluoroalkyl; R.sub.7 and R.sub.8 are, independently, hydrogen or an acyl substituent selected from the group consisting of formyl, alkanoyl, alkenoyl, alkoxycarbonyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is a phenyl group with either two or three substituents of the following formula: ##STR2## wherein the positions of substitution are R.sub.2,R.sub.3 -, R.sub.2,R.sub.4 -, R.sub.2,R.sub.5 -, R.sub.2,R.sub.6 -, R.sub.3,R.sub.4 -, R.sub.3,R.sub.5 -, and R.sub.2,R.sub.4,R.sub.6 - and R.sub.2 is methyl, ethyl, fluoro, chloro, methoxy or trifluoromethyl; R.sub.3 is methyl, ethyl, fluoro, chloro, methoxy or trifluoromethyl; R.sub.4 is methyl, fluoro, bromo, methoxy or cyano; R.sub.5 is methyl, fluoro, chloro, methoxy, cyano or trifluoromethyl; R.sub.6 is methyl, fluoro, chloro, or methoxy; or a pharmaceutically acceptable salt thereof, relax smooth muscles.

摘要翻译： 下式的化合物：其中R 1是直链烷基，支链烷基，环烷基，羟基烷基，氟烷基或多氟烷基; R 7和R 8独立地是氢或选自甲酰基，烷酰基，烯酰基，烷氧基羰基，烷基磺酰基，芳酰基，芳基烯酰基，芳基磺酰基，芳基烷酰基或芳基烷基磺酰基的酰基取代基。 A是具有下式的两个或三个取代基的苯基：其中取代的位置是R2，R3-，R2，R4-，R2，R5-，R2，R6-，R3，R4-， R 3，R 5和R 2，R 4，R 6和R 2是甲基，乙基，氟，氯，甲氧基或三氟甲基; R3是甲基，乙基，氟，氯，甲氧基或三氟甲基; R4是甲基，氟，溴，甲氧基或氰基; R5是甲基，氟，氯，甲氧基，氰基或三氟甲基; R6是甲基，氟，氯或甲氧基; 或其药学上可接受的盐，使平滑肌松弛。

公开(公告)号：US5872139A

公开(公告)日：1999-02-16

申请号：US873132

申请日：1997-06-10

申请人： David R. Herbst ,  John A. Butera ,  Russell F. Graceffa

发明人： David R. Herbst ,  John A. Butera ,  Russell F. Graceffa

IPC分类号： C07D213/38 ,  C07D307/81 ,  C07D307/82 ,  A61K31/34 ,  A61K31/44 ,  C07D213/50

CPC分类号： C07D307/82 ,  C07D213/38 ,  C07D307/81

摘要： The compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are, independently, hydrogen, straight chain alkyl, branched chain alkyl, cycloalkyl, bicycloalkyl or aralkyl, wherein the aromatic moiety of the aralkyl group may be optionally substituted with one to three straight chain alkyl, halogen, nitro, cyano, alkoxy, alkoxycarbonyl, trifluoromethyl or trifluoromethoxy groups; R.sub.3 is hydrogen, formyl, alkanoyl, alkenoyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is selected from the group consisting of: ##STR2## wherein n is 0 or 1; R.sub.4, R.sub.5 and R.sub.6 are, independently, cyano, nitro, amino, alkyl, perfluoroalkyl, alkoxy, perfluoroalkoxy, alkylamino, dialkylamino, sulfamyl, alkylsulfonamido, arylsulfonamido, alkylcarboxamido, arylcarboxamido, alkanoyl, alkylsulfonyl, perfluoroalkylsulfonyl, arylsulfonyl, chloro, bromo, fluoro, iodo, 1-imidazolyl, carboxyl or hydrogen; or a pharmaceutically acceptable salt thereof, relax smooth muscles.

摘要翻译： 下式的化合物：其中R 1和R 2独立地是氢，直链烷基，支链烷基，环烷基，双环烷基或芳烷基，其中芳烷基的芳族部分可以任选地被一个 三个直链烷基，卤素，硝基，氰基，烷氧基，烷氧基羰基，三氟甲基或三氟甲氧基; R 3是氢，甲酰基，烷酰基，烯酰基，烷基磺酰基，芳酰基，芳基烯酰基，芳基磺酰基，芳基烷酰基或芳基烷基磺酰基; A选自由以下组成的组： 其中n为0或1; R 4，R 5和R 6独立地是氰基，硝基，氨基，烷基，全氟烷基，烷氧基，全氟烷氧基，烷基氨基，二烷基氨基，氨基磺酰基，烷基磺酰氨基，芳基磺酰氨基，烷基羧酰氨基，芳基羧酰氨基，烷酰基，烷基磺酰基，全氟烷基磺酰基，芳基磺酰基，氯，溴，氟 ，碘，1-咪唑基，羧基或氢; 或其药学上可接受的盐，使平滑肌松弛。

公开(公告)号：US07601856B2

公开(公告)日：2009-10-13

申请号：US11828457

申请日：2007-07-26

申请人： Gregory S. Welmaker ,  Matthew A. Wilson ,  Geraldine McFarlane ,  Joan E. Sabalski ,  John A. Butera ,  Eugene J. Trybulski ,  David R. Herbst

发明人： Gregory S. Welmaker ,  Matthew A. Wilson ,  Geraldine McFarlane ,  Joan E. Sabalski ,  John A. Butera ,  Eugene J. Trybulski ,  David R. Herbst

IPC分类号： C07D307/90

CPC分类号： C07D307/91 ,  C07D307/93 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D491/113

摘要： The present invention is directed to compounds of Formula I: that are potassium channel modulators and pharmaceutical compositions thereof. The present invention is further directed to methods of treatment using the compounds and pharmaceutical compositions of the invention. The present invention is still further directed to synthetic processes for producing the compounds of the invention.

摘要翻译： 本发明涉及式I化合物：其是钾通道调节剂及其药物组合物。 本发明还涉及使用本发明的化合物和药物组合物的治疗方法。 本发明还涉及用于制备本发明化合物的合成方法。

公开(公告)号：US3943148A

公开(公告)日：1976-03-09

申请号：US279411

申请日：1972-08-10

申请人： David R. Herbst ,  Herchel Smith

发明人： David R. Herbst ,  Herchel Smith

IPC分类号： C07D471/16 ,  C07D209/12 ,  C07D209/14

CPC分类号： C07D471/16

摘要： Substituted 1,2,4,5,6,7,8,9-octahydro-3H-azecino[5,4-b]-indoles and substituted 1,2,3,4,5,6,7,8-octahydroazonino[5,4-b]-indoles are prepared by cleavage of the corresponding quaternary alkyl iodide salts with lithium in liquid ammonia. The products possess diuretic activity.

摘要翻译： 取代的1,2,4,5,6,7,8,9-八氢-3H-氮杂[5,4-b] - 吲哚和取代的1,2,3,4,5,6,7,8-八氢氮杂 [5,4-b] - 吲哚通过在液氨中用锂裂解相应的季烷基碘盐来制备。 产品具有利尿活性。