公开(公告)号：EP0395313A3

公开(公告)日：1991-05-08

申请号：EP90304251.3

申请日：1990-04-20

申请人： AMERICAN HOME PRODUCTS CORPORATION ,  JOHN WYETH & BROTHER LIMITED

发明人： Cliffe, Ian Anthony ,  Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick

IPC分类号： C07D295/08 ,  C07D295/12 ,  C07D295/14 ,  A61K31/495 ,  C07D239/42

CPC分类号： C07D295/145 ,  C07C2601/14 ,  C07D239/42 ,  C07D295/088 ,  C07D295/13 ,  C07D295/15

摘要： Compounds of the formula
in which R¹ is alkyl; R² and R³ are alkyl or taken together they are polymethylene, R² and R³ complete a 5-norbornen-2-yl moiety; X is -CO₂-, -OCO-, -OCO₂-, -N(R⁷)CO-, -NHNHCO-, -ON(R⁷)CO-, -CON(R⁷)-, -N(R⁷)CO₂-, -OCON(R⁷)- or -N(R⁷)CON(R⁸)-, wherein R⁷ and R⁸ are, independently, hydrogen, alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl, alkoxy, cyano, nitro or perhalomethyl; R⁴ is hydrogen or alkyl; R⁵ is hydrogen, alkyl, hydroxyalkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino, or dialkylamino; R⁶ is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl, any of which may be substituted by one or more hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; n is one of the integers 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is -CON(R⁷)- and R⁷ is alkyl, R⁶ is other than 2-pyrimidinyl, are antidepressant and/or anxiolytic agents.

摘要翻译： 其中R 1是烷基的式的化合物; R 2和R 3是烷基或一起它们是聚亚甲基，R 2和R 3完成5-降冰片烯-2-基部分; X是-CO 2 - ， - OCO - ， - OCO 2 - ， - N（R 7）CO - ， - NHNHCO-，-ON（R 7）CO-，-CON（R 7） -N（R 7）CO 2 - ， - OCON（R 7） - 或-N（R 7）CON（R 8） - ，其中R 7和R 8是 烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是卤素，烷基，烷氧基，氰基，硝基或全卤代甲基; R 4是氢或烷基; R 5是氢，烷基，羟基烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是羟基，卤素，烷基，烷氧基，三氟甲基，硝基，氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; R 6是苯基，苄基，2-，3-或4-吡啶基，2-嘧啶基或2-吡嗪基，其中任何一个可以被一个或多个羟基，卤素，烷基，烷氧基，三氟甲基，硝基， 氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; n是整数1,2,3,4或5之一; 或其药学上可接受的盐，条件是当X是-CON（R 7） - 且R 7是烷基时，R 6不是2-嘧啶基，是抗抑郁剂和/或抗焦虑剂。

公开(公告)号：EP0737678B1

公开(公告)日：2002-06-19

申请号：EP96302420.3

申请日：1996-04-04

申请人： AMERICAN HOME PRODUCTS CORPORATION ,  JOHN WYETH & BROTHER LIMITED

发明人： Yardley, John Patrick ,  Fletcher, Horace ,  Kelly, Michael Gerard ,  White, Alan Chapman

IPC分类号： C07D209/08 ,  A61K31/40

CPC分类号： C07D209/08

公开(公告)号：EP0955296A2

公开(公告)日：1999-11-10

申请号：EP99108070.6

申请日：1990-04-20

申请人： AMERICAN HOME PRODUCTS CORPORATION ,  JOHN WYETH & BROTHER LIMITED

发明人： Cliffe, Ian Anthony ,  Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick

IPC分类号： C07D295/12 ,  C07D295/08 ,  C07D239/42 ,  C07D295/14 ,  A61K31/495

CPC分类号： C07D295/145 ,  C07C2601/14 ,  C07D239/42 ,  C07D295/088 ,  C07D295/13 ,  C07D295/15

摘要： Compounds of the formula:
in which R 1 is alkyl; R 2 and R 3 are alkyl or taken together they are polymethylene, R 2 and R 3 complete a 5-norbornen-2-yl moiety; X is -CO 2 -, -OCO-, -OCO 2 -, -N(R 7 )CO-, -NHNHCO-, -ON(R 7 )CO-, -CON(R 7 )-, -N(R 7 )CO 2 -, -OCON(R 7 )- or -N(R 7 )CON(R 8 )-, wherein R 7 and R 8 are, independently, hydrogen, alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl, alkoxy, cyano, nitro or perhalomethyl; R 4 is hydrogen or alkyl; R 5 is hydrogen, alkyl, hydroxyalkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; R 6 is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl, any of which may be substituted by one or more hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; n is one of the integers 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is -CON(R 7 )- and R 7 is alkyl, R 6 is other than 2-pyrimidinyl, are antidepressant and/or anxiolytic agents.

摘要翻译： 下式的化合物：其中R 1是烷基的 R 2和R 3是烷基或一起它们是聚亚甲基，R 2和R 3完成5-降冰片烯-2-基部分; X是-CO 2 - ， - OCO - ， - OCO 2 - ， - N（R 7）CO - ， - NHNHCO-，-ON（R 7）CO-，-CON（R 7） -N（R 7）CO 2 - ， - OCON（R 7） - 或-N（R 7）CON（R 8） - ，其中R 7和R 8是 烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是卤素，烷基，烷氧基，氰基，硝基或全卤代甲基; R 4是氢或烷基; R 5是氢，烷基，羟基烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是羟基，卤素，烷基，烷氧基，三氟甲基，硝基，氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; R 6是苯基，苄基，2-，3-或4-吡啶基，2-嘧啶基或2-吡嗪基，其中任何一个可以被一个或多个羟基，卤素，烷基，烷氧基，三氟甲基，硝基， 氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; n是整数1,2,3,4或5之一; 或其药学上可接受的盐，条件是当X是-CON（R 7） - 且R 7是烷基时，R 6不是2-嘧啶基，是抗抑郁剂和/或抗焦虑剂。

公开(公告)号：EP0112669A2

公开(公告)日：1984-07-04

申请号：EP83307435.4

申请日：1983-12-07

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： Husbands, George Edward Morris ,  Yardley, John Patrick ,  Muth, Eric Anthony

IPC分类号： C07C93/14 ,  C07C93/24 ,  C07C91/23 ,  C07C121/75 ,  C07C103/76 ,  A61K31/135 ,  A61K31/22

CPC分类号： C07D265/14 ,  C07C215/42 ,  C07C215/64 ,  C07C215/70 ,  C07C235/34 ,  C07C255/36 ,  C07C255/37 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/16 ,  C07C2601/18

摘要： Novel phenethylamine derivatives are central nervous system antidepressants. The compounds are those having the formula
where A is
where the dotted line represents optional unsaturation;

R 1 and R 7 are, independently, hydrogen or C 1 -C 6 alkyl;
R 2 is C 1 -C 6 alkyl;
R 4 is hydrogen, C 1 -C 4 alkyl, formyl or C 2 -C 7 alkanoly;
R 5 and R 6 are hydrogen or defined substituents and n is 0,1,2,3, or 4 and their pharmaceutically acceptable salts. Novel intermediates for the preparation of these compounds include those of the formulae

摘要翻译： 新型苯乙胺衍生物是中枢神经系统抗抑郁药。 化合物是具有式的化合物，其中虚线表示任选的不饱和键; R 1和R 7独立地是氢或C 1 -C 6烷基; R2是C1-C6烷基; R4是氢，C1-C4烷基，甲酰基或C2-C7链烷醇; P5和R6是氢或定义的取代基，n是0,1,2,3或4及其药学上可接受的盐。 用于制备这些化合物的新型中间体包括式 1的那些

公开(公告)号：EP0539057B1

公开(公告)日：1997-07-16

申请号：EP92309160.7

申请日：1992-10-08

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： Baudy, Reinhardt Bernhard ,  Fletcher III, Horace ,  Yardley, John Patrick

IPC分类号： C07F9/6506 ,  A61K31/675

CPC分类号： C07F9/65068

公开(公告)号：EP0737678A1

公开(公告)日：1996-10-16

申请号：EP96302420.3

申请日：1996-04-04

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： Yardley, John Patrick ,  Fletcher, Horace ,  Kelly, Michael Gerard ,  White, Alan Chapman

IPC分类号： C07D209/08 ,  A61K31/40

CPC分类号： C07D209/08

摘要： This invention provides anxiolytic/antidepressant agents of the formula:

in which
R 1 is alkyl of 1 to 6 carbon atoms, cycloalkyl of 5 to 7 carbon atoms, aryl of 6 to 10 carbon atoms or arylalkyl of 7 to 12 carbon atoms;
R 2 is hydrogen or alkyl of 1 to 6 carbon atoms;
R 3 is phenyl, benzyl, substituted phenyl, or substituted benzyl in which the substituents are hydroxy, halo, alkoxy of 1 to 6 carbon atoms, trifluoromethyl, nitro, cyano, alkoxycarbonyl of 2 to 7 carbon atoms, amino or dialkylamino in which each alkyl group contains 1 to 6 carbon atoms;
or a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明提供下式的抗焦虑/抗抑郁药：其中R1是1-6个碳原子的烷基，5-7个碳原子的环烷基，6-10个碳原子的芳基或7-12个碳原子的芳基烷基; R2是氢或1至6个碳原子的烷基; 其中取代基为羟基，卤素，1-6个碳原子的烷氧基，三氟甲基，硝基，氰基，2-7个碳原子的烷氧基羰基，氨基或二烷基氨基，其中各烷基 基团含有1至6个碳原子; 或其药学上可接受的盐。

公开(公告)号：EP0395313A2

公开(公告)日：1990-10-31

申请号：EP90304251.3

申请日：1990-04-20

申请人： AMERICAN HOME PRODUCTS CORPORATION ,  JOHN WYETH & BROTHER LIMITED

发明人： Cliffe, Ian Anthony ,  Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick

IPC分类号： C07D295/08 ,  C07D295/12 ,  C07D295/14 ,  A61K31/495 ,  C07D239/42

CPC分类号： C07D295/145 ,  C07C2601/14 ,  C07D239/42 ,  C07D295/088 ,  C07D295/13 ,  C07D295/15

摘要： Compounds of the formula
in which R¹ is alkyl; R² and R³ are alkyl or taken together they are polymethylene, R² and R³ complete a 5-norbornen-2-yl moiety; X is -CO₂-, -OCO-, -OCO₂-, -N(R⁷)CO-, -NHNHCO-, -ON(R⁷)CO-, -CON(R⁷)-, -N(R⁷)CO₂-, -OCON(R⁷)- or -N(R⁷)CON(R⁸)-, wherein R⁷ and R⁸ are, independently, hydrogen, alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl, alkoxy, cyano, nitro or perhalomethyl; R⁴ is hydrogen or alkyl; R⁵ is hydrogen, alkyl, hydroxyalkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino, or dialkylamino; R⁶ is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl, any of which may be substituted by one or more hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; n is one of the integers 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is -CON(R⁷)- and R⁷ is alkyl, R⁶ is other than 2-pyrimidinyl, are antidepressant and/or anxiolytic agents.

摘要翻译： 其中R 1是烷基的式的化合物; R 2和R 3是烷基或一起它们是聚亚甲基，R 2和R 3完成5-降冰片烯-2-基部分; X是-CO 2 - ， - OCO - ， - OCO 2 - ， - N（R 7）CO - ， - NHNHCO-，-ON（R 7）CO-，-CON（R 7） -N（R 7）CO 2 - ， - OCON（R 7） - 或-N（R 7）CON（R 8） - ，其中R 7和R 8是 烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是卤素，烷基，烷氧基，氰基，硝基或全卤代甲基; R 4是氢或烷基; R 5是氢，烷基，羟基烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是羟基，卤素，烷基，烷氧基，三氟甲基，硝基，氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; R 6是苯基，苄基，2-，3-或4-吡啶基，2-嘧啶基或2-吡嗪基，其中任何一个可以被一个或多个羟基，卤素，烷基，烷氧基，三氟甲基，硝基， 氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; n是整数1,2,3,4或5之一; 或其药学上可接受的盐，条件是当X是-CON（R 7） - 且R 7是烷基时，R 6不是2-嘧啶基，是抗抑郁剂和/或抗焦虑剂。

公开(公告)号：EP0955296A3

公开(公告)日：2000-01-19

申请号：EP99108070.6

申请日：1990-04-20

申请人： AMERICAN HOME PRODUCTS CORPORATION ,  JOHN WYETH & BROTHER LIMITED

发明人： Cliffe, Ian Anthony ,  Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick

IPC分类号： C07D295/12 ,  C07D295/08 ,  C07D239/42 ,  C07D295/14 ,  A61K31/495

CPC分类号： C07D295/145 ,  C07C2601/14 ,  C07D239/42 ,  C07D295/088 ,  C07D295/13 ,  C07D295/15

摘要： Compounds of the formula: in which R 1 is alkyl; R 2 and R 3 are alkyl or taken together they are polymethylene, R 2 and R 3 complete a 5-norbornen-2-yl moiety; X is -CO 2 -, -OCO-, -OCO 2 -, -N(R 7 )CO-, -NHNHCO-, -ON(R 7 )CO-, -CON(R 7 )-, -N(R 7 )CO 2 -, -OCON(R 7 )- or -N(R 7 )CON(R 8 )-, wherein R 7 and R 8 are, independently, hydrogen, alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl, alkoxy, cyano, nitro or perhalomethyl; R 4 is hydrogen or alkyl; R 5 is hydrogen, alkyl, hydroxyalkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; R 6 is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl, any of which may be substituted by one or more hydroxy, halo, alkyl, alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; n is one of the integers 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is -CON(R 7 )- and R 7 is alkyl, R 6 is other than 2-pyrimidinyl, are antidepressant and/or anxiolytic agents.

摘要翻译： 其中R 1是烷基的式的化合物; R 2和R 3是烷基或一起它们是聚亚甲基，R 2和R 3完成5-降冰片烯-2-基部分; X是-CO 2 - ， - OCO - ， - OCO 2 - ， - N（R 7）CO - ， - NHNHCO-，-ON（R 7）CO-，-CON（R 7） -N（R 7）CO 2 - ， - OCON（R 7） - 或-N（R 7）CON（R 8） - ，其中R 7和R 8是 烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是卤素，烷基，烷氧基，氰基，硝基或全卤代甲基; R 4是氢或烷基; R 5是氢，烷基，羟基烷基，苯基，苄基，取代的苯基或取代的苄基，其中取代基是羟基，卤素，烷基，烷氧基，三氟甲基，硝基，氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; R 6是苯基，苄基，2-，3-或4-吡啶基，2-嘧啶基或2-吡嗪基，其中任何一个可以被一个或多个羟基，卤素，烷基，烷氧基，三氟甲基，硝基， 氰基，烷氧基，甲酰胺基，氨基，烷基氨基或二烷基氨基; n是整数1,2,3,4或5之一; 或其药学上可接受的盐，条件是当X是-CON（R 7） - 且R 7是烷基时，R 6不是2-嘧啶基，是抗抑郁剂和/或抗焦虑剂。

公开(公告)号：EP0343961A3

公开(公告)日：1991-01-16

申请号：EP89305255.5

申请日：1989-05-24

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick ,  Childers, Wayne Everett, Jr.

IPC分类号： C07D295/12 ,  A61K31/495 ,  C07D239/42 ,  A61K31/505 ,  C07D407/12 ,  C07D209/42 ,  A61K31/40 ,  C07D307/84 ,  A61K31/34

CPC分类号： C07D239/42 ,  C07D209/42 ,  C07D295/13

摘要： The invention discloses compounds of the formula (I)
wherein R¹ is 1-adamantyl, 3-methyl-1-adamantyl, 3-noradamantyl, unsubstituted or substituted-2-­indolyl, 3-indolyl, 2-benzofuranyl and 3-benzofuranyl wherein the substituents are selected from lower alkyl, lower alkoxy and halo; R² is unsubstituted or substituted phenyl, benzyl, pyridinyl, pyrimidinyl or pyrazinyl, wherein the substituents are selected from lower alkyl, lower alkoxy, trifluoromethyl and halo; R³ is H or lower alkyl of 1 to 3 carbon atoms, n is the integer 0 or 1; m is an integer from 2 to 5, and the pharmaceutically acceptable salts thereof which possess central nervous system activity.

公开(公告)号：EP0343961A2

公开(公告)日：1989-11-29

申请号：EP89305255.5

申请日：1989-05-24

申请人： AMERICAN HOME PRODUCTS CORPORATION

发明人： Abou-Gharbia, Magid Abdel-Megid ,  Yardley, John Patrick ,  Childers, Wayne Everett, Jr.

IPC分类号： C07D295/12 ,  A61K31/495 ,  C07D239/42 ,  A61K31/505 ,  C07D407/12 ,  C07D209/42 ,  A61K31/40 ,  C07D307/84 ,  A61K31/34

CPC分类号： C07D239/42 ,  C07D209/42 ,  C07D295/13

摘要： The invention discloses compounds of the formula (I)
wherein R¹ is 1-adamantyl, 3-methyl-1-adamantyl, 3-noradamantyl, unsubstituted or substituted-2-­indolyl, 3-indolyl, 2-benzofuranyl and 3-benzofuranyl wherein the substituents are selected from lower alkyl, lower alkoxy and halo; R² is unsubstituted or substituted phenyl, benzyl, pyridinyl, pyrimidinyl or pyrazinyl, wherein the substituents are selected from lower alkyl, lower alkoxy, trifluoromethyl and halo; R³ is H or lower alkyl of 1 to 3 carbon atoms, n is the integer 0 or 1; m is an integer from 2 to 5, and the pharmaceutically acceptable salts thereof which possess central nervous system activity.

摘要翻译： 本发明公开了式（I）的化合物，其中R 1是1-金刚烷基，3-甲基-1-金刚烷基，3-降金刚烷基，未取代的或取代的-2-吲哚基，3-吲哚基，2-苯并呋喃基 和3-苯并呋喃基，其中取代基选自低级烷基，低级烷氧基和卤素; R 2是未取代或取代的苯基，苄基，吡啶基，嘧啶基或吡嗪基，其中取代基选自低级烷基，低级烷氧基，三氟甲基和卤素; R 3是H或1至3个碳原子的低级烷基，n是整数0或1; m是2至5的整数，及其药学上可接受的盐，其具有中枢神经系统活性。