公开(公告)号：US4739072A

公开(公告)日：1988-04-19

申请号：US888254

申请日：1986-07-23

申请人： Alexander W. Oxford ,  Colin D. Eldred ,  Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

发明人： Alexander W. Oxford ,  Colin D. Eldred ,  Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

IPC分类号： C07D403/06 ,  A61K31/415 ,  C07C221/00 ,  C07C225/14 ,  C07D233/60 ,  C07D233/61 ,  C07D521/00 ,  C07D403/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08

摘要： The invention relates to a process for the preparation of a compound of general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4)alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-(C.sub.1-3)alkyl group, and one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.1-3)alkyl group and each of the other two groups, which may be the same or different, represent a hydrogen atom or a C.sub.1-6 alkyl group;or a salt or protected derivative thereof, by cyclization of a compound of general formula (II) ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, or a salt or a protected derivative thereof.The compounds of formula (I) are potent and selective antagonists at "neuronal" 5-hydroxytryptamine receptors.

摘要翻译： 本发明涉及一种制备通式（I）化合物的方法，其中R1表示氢原子或C1-10烷基，C3-7环烷基，C3-7环烷基 - （C1- 4）烷基，C 3-6烯基，C 3-10炔基，苯基或苯基 - （C 1-3）烷基，并且由R 2，R 3和R 4表示的基团之一是氢原子或C 1-6烷基，C 3 -7环烷基，C 2-6烯基或苯基 - （C 1-3）烷基，其它可以相同或不同的两个基团表示氢原子或C 1-6烷基; 或其盐或被保护的衍生物，通过使通式（II）化合物（II）其中R 1，R 2，R 3和R 4如上所定义的化合物或其盐或其保护的衍生物环化。 式（I）化合物是“神经元”5-羟色胺受体的有效和选择性拮抗剂。

公开(公告)号：US4939144A

公开(公告)日：1990-07-03

申请号：US260680

申请日：1988-10-21

申请人： Ian H. Coates ,  David C. Humber ,  James A. Bell ,  George B. Ewan ,  Alexander W. Oxford ,  William L. Mitchell

发明人： Ian H. Coates ,  David C. Humber ,  James A. Bell ,  George B. Ewan ,  Alexander W. Oxford ,  William L. Mitchell

IPC分类号： A61K31/415 ,  A61P1/00 ,  A61P1/08 ,  A61P25/00 ,  A61P25/04 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D521/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06

摘要： The invention relates to ketones of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## one of the groups represented by R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenyl C.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;n represents 1, 2 or 3;Q represents a hydrogen atom, a halogen atom, or a hydroxy, C.sub.1-4 alkoxy, phenyl C.sub.1-3 alkoxy or C.sub.1-6 alkyl group, or a group --NR.sup.4 R.sup.5 or --CONR.sup.4 R.sup.5, (wherein R.sup.4 and R.sup.5, which may be the same or different, each represents a hydrogen atom or a C.sub.1-4 alkyl or C.sub.3-4 alkenyl group, or together with the nitrogen atom to which they are attached form a saturated 5 to 7 membered ring);and X represents an oxygen or a sulphur atom, or, when Im represents an imidazolyl group of formula (c) and n represents 1 or 3, X may also represent the group NR.sup.6, wherein R.sup.6 represents a hydrogen atom or a group selected from C.sub.1-10 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl C.sub.1-4 alkyl, phenyl, phenyl C.sub.1-3 alkyl, --CO.sub.2 R.sup.7, --COR.sup.7, --CONR.sup.7 R.sup.8 or --SO.sub.2 R.sup.7 (wherein R.sup.7 and R.sup.8, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl, or C.sub.3-7 cycloalkyl group, or a phenyl or phenyl C.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.7 does not represent a hydrogen atom when R.sup.6 represents a group --CO.sub.2 R.sup.7); and physiologically acceptable salts and solvates thereof.The compounds are potent and selective antagonists of the effect of 5-HT and 5-HT.sub.3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety, and nausea and vomiting.

公开(公告)号：US4855314A

公开(公告)日：1989-08-08

申请号：US1469

申请日：1987-01-08

申请人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb ,  Michael D. Dowle ,  Keith Mills ,  Colin D. Eldred

发明人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb ,  Michael D. Dowle ,  Keith Mills ,  Colin D. Eldred

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/405 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16

CPC分类号： C07D209/16

摘要： Compounds are disclosed of formula (I): ##STR1## wherein R.sub.1 is halogen, a C.sub.1-3 alkoxy, R.sub.6 R.sub.7 NCO(CH.sub.2).sub.p --, R.sub.6 CONH(CH.sub.2).sub.p --, R.sub.6 R.sub.7 NSO.sub.2 (CH.sub.2).sub.p --, or R.sub.8 SO.sub.2 NH(CH.sub.2).sub.p -- (where R.sub.6 and R.sub.7 each represents hydrogen or C.sub.1-3 alkyl, R.sub.8 represents C.sub.1-3 alkyl and p is zero or 1);R.sub.2 represents hydrogen or C.sub.1-3 alkyl; R.sub.3 represents hydrogen or C.sub.1-3 alkyl;R.sub.4 and R.sub.5 each represents hydrogen, C.sub.1-3 alkyl or 2-propenyl;A represents --CO-- or --SO.sub.2 --;n represents an integer from 2 to 5; and m represents zero or an integer from 1 to 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. The compounds may be formulated as pharmaceutical compositions with physiologically acceptable carriers or excipients for administration by any convenient route. Various methods for the preparation of the compounds (I) are disclosed.

公开(公告)号：US5221687A

公开(公告)日：1993-06-22

申请号：US934307

申请日：1992-08-25

申请人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Michael B. Tyers

发明人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Michael B. Tyers

IPC分类号： A61K31/00 ,  A61K31/445 ,  A61K31/55

CPC分类号： A61K31/00 ,  A61K31/445 ,  A61K31/55

摘要： The invention relates to the use of compounds of formula (I) ##STR1## wherein Im represents an imidazolyl group of formula: ##STR2## and R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, phenylC.sub.1-3 alkyl, phenylmethoxymethyl, phenoxyethyl, phenoxymethyl, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 or --SO.sub.2 R.sup.5 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenylC.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.5 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.5 or --SO.sub.2 R.sup.5);one of the groups represented by R.sup.2, R.sup.3 and R4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;and n represents 2 or 3,and physiologically acceptable salts and solvates thereof for the manufacture of a medicament for the treatment of depression.

摘要翻译： 本发明涉及式（I）化合物其中Im表示下式的咪唑基，R1表示氢原子或选自C 1-6烷基，C 3-6烯基， C 3-10炔基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，苯基，苯基C 1-3烷基，苯基甲氧基甲基，苯氧基乙基，苯氧基甲基，-CO 2 R 5，-COR 5，-CONR 5 R 6或-SO 2 R 5（其中R 5和R 6可以相同或不同 各自表示氢原子，C 1-6烷基或C 3-7环烷基，或苯基或苯基C 1-4烷基，其中苯基任选被一个或多个C 1-4烷基，C 1-4烷氧基或羟基或卤素 原子，条件是当R 1表示-CO 2 R 5或-SO 2 R 5基团时，R 5不表示氢原子）; 由R 2，R 3和R 4表示的基团之一是氢原子或C 1-6烷基，C 3-7环烷基，C 3-6烯基，苯基或苯基C 1-3烷基，其它两个基团可以相同或 不同，代表氢原子或C1-6烷基; 和n表示2或3，以及其生理上可接受的盐和溶剂合物，用于制备用于治疗抑郁症的药物。

公开(公告)号：US4140713A

公开(公告)日：1979-02-20

申请号：US873765

申请日：1978-01-31

申请人： Alexander W. Oxford ,  Ian H. Coates

发明人： Alexander W. Oxford ,  Ian H. Coates

IPC分类号： A61K31/165 ,  A61P25/02 ,  C07C67/00 ,  C07C231/00 ,  C07C231/02 ,  C07C231/06 ,  C07C231/12 ,  C07C237/30 ,  C07C301/00 ,  C07C303/40 ,  C07C311/08 ,  C07C313/00 ,  C07D295/112 ,  C07D295/135 ,  C07C91/06 ,  C07C143/78 ,  C07C143/80

CPC分类号： C07D295/112 ,  C07D295/135

摘要： Compounds of the general formula: ##STR1## and non-toxic physiologically acceptable salts thereof, in which R.sub.1 is a halogen atom or a group NR.sub.2 R.sub.3 ;R.sub.2 and R.sub.3, which may be the same or different, are hydrogen or (C.sub.1 -C.sub.6) straight or branched chain alkyl or R.sub.2 and R.sub.3 may, together with the nitrogen atom, form a 5 or 6 membered heterocyclic ring which may contain a further hetero atom selected from O, N or S; or R.sub.2 may be hydrogen and R.sub.3 may by group R.sub.4 CO or R.sub.4 SO.sub.2 where R.sub.4 is hydrogen or alkyl (C.sub.1-4);R.sub.5 is hydrogen or one or more halogen atoms or hydroxy or alkoxy (C.sub.1-4) groups; andX is CH.sub.2, O or a group NR.sub.6 where R.sub.6 is hydrogen or alkyl (C.sub.1-4). These compounds block .beta.-adrenoreceptors.

摘要翻译： 其中R 1为卤素原子或NR 2 R 3基团的通式为：其无毒生理学上可接受的盐; R2和R3可以相同或不同，是氢或（C1-C6）直链或支链烷基或R2和R3可以与氮原子一起形成5或6元杂环，其可以含有另外 选自O，N或S的杂原子; 或R 2可以是氢，R 3可以通过R4CO或R4SO2，其中R4是氢或烷基（C1-4）; R5是氢或一个或多个卤素原子或羟基或烷氧基（C1-4）基团; 并且X是CH 2，O或NR 6，其中R 6是氢或烷基（C 1-4）。 这些化合物阻断β-肾上腺素受体。

公开(公告)号：US5229407A

公开(公告)日：1993-07-20

申请号：US911395

申请日：1992-07-10

申请人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Michael B. Tyers

发明人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Michael B. Tyers

IPC分类号： A61K31/00 ,  A61K31/445 ,  A61K31/55

CPC分类号： A61K31/445 ,  A61K31/00 ,  A61K31/55

摘要： The invention relates to the use of compounds of formula (I) ##STR1## wherein Im represents an imidazolyl group of formula: ##STR2## and R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, phenylC.sub.1-3 alkyl, phenylmethoxymethyl, phenoxyethyl, phenoxymethyl, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 or --SO.sub.2 R.sup.5 (wherein R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenylC.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.5 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.5 or --SO.sub.2 R.sup.5);one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;and n represents 2 or 3,and physiologically acceptable salts and solvates thereof for the manufacture of a medicament for the treatment of a cognitive disorder.

摘要翻译： 本发明涉及式（I）化合物其中Im表示下式的咪唑基，R1表示氢原子或选自C 1-6烷基，C 3-6烯基， C 3-10炔基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，苯基，苯基C 1-3烷基，苯基甲氧基甲基，苯氧基乙基，苯氧基甲基，-CO 2 R 5，-COR 5，-CONR 5 R 6或-SO 2 R 5（其中R 5和R 6可以相同或不同 各自表示氢原子，C 1-6烷基或C 3-7环烷基，或苯基或苯基C 1-4烷基，其中苯基任选被一个或多个C 1-4烷基，C 1-4烷氧基或羟基或卤素 原子，条件是当R 1表示-CO 2 R 5或-SO 2 R 5基团时，R 5不表示氢原子）; 由R 2，R 3和R 4表示的基团之一是氢原子或C 1-6烷基，C 3-7环烷基，C 3-6烯基，苯基或苯基C 1-3烷基，其它两个基团可以相同或 不同，代表氢原子或C1-6烷基; 和n表示2或3，以及其生理上可接受的盐和溶剂合物，用于制备用于治疗认知障碍的药物。

公开(公告)号：US4994483A

公开(公告)日：1991-02-19

申请号：US443874

申请日：1989-11-30

申请人： Alexander W. Oxford ,  Brian Evans ,  Michael D. Dowle ,  Ian H. Coates

发明人： Alexander W. Oxford ,  Brian Evans ,  Michael D. Dowle ,  Ian H. Coates

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  C07C67/00 ,  C07C301/00 ,  C07C311/02 ,  C07C311/35 ,  C07D209/08 ,  C07D209/10 ,  C07D209/12 ,  C07D209/16 ,  C07D209/18 ,  C07D209/48

CPC分类号： C07D209/48 ,  C07C205/44 ,  C07C309/00 ,  C07D209/08 ,  C07D209/10 ,  C07D209/12 ,  C07D209/16 ,  C07D209/18 ,  Y10S514/93

摘要： Indole derivatives are disclosed of the general formula (I): ##STR1## wherein R.sub.1 is hydrogen, C.sub.1-6 alkyl or C.sub.3-6 alkenyl; R.sub.2 is a hydrogen, C.sub.1-3 alkyl, C.sub.3-6 alkenyl, phenyl, phen(C.sub.1-4)alkyl or C.sub.5-7 cycloalkyl; R.sub.3 and R.sub.4 are hydrogen, C.sub.1-3 alkyl or propenyl groups or together form an aralkylidene group; Alk is C.sub.2 -C.sub.3 alkylene chain and A is C.sub.2 -C.sub.5 alkylene chainand its physiologically acceptable salts and solvates.The compounds may be prepared, for example, by cyclization of a compound of general formula (II): ##STR2## where Q is the group NR.sub.3 R.sub.4 or a protected derivative thereof or a leaving group and R.sub.1 l, R.sub.2, R.sub.3, R.sub.4, A and Alk are as defined for formula (I).The compounds have a selective vosoconstrictor action and are useful in treating pain such as migraine. The compounds may be formulated as pharmaceutical compositions in conventional manner, preferably for oral administration.

摘要翻译： 公开了通式（I）的吲哚衍生物：其中R 1是氢，C 1-6烷基或C 3-6烯基; R 2是氢，C 1-3烷基，C 3-6烯基，苯基，苯基（C 1-4）烷基或C 5-7环烷​​基; R3和R4是氢，C1-3烷基或丙烯基或一起形成亚烷基; Alk是C2-C3亚烷基链，A是C2-C5亚烷基链及其生理上可接受的盐和溶剂合物。 化合物可以例如通过环化通式（II）的化合物来制备：其中Q是NR3R4基团或其保护的衍生物或离去基团，R1，R2，R3 ，R4，A和Alk如式（I）所定义。 该化合物具有选择性的血管收缩作用，并且可用于治疗疼痛如偏头痛。 化合物可以以常规方式配制成药物组合物，优选用于口服给药。

公开(公告)号：US4870096A

公开(公告)日：1989-09-26

申请号：US940652

申请日：1986-12-11

申请人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb

发明人： Alexander W. Oxford ,  Ian H. Coates ,  David E. Bays ,  Colin F. Webb

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16

CPC分类号： C07D209/16

摘要： Indoles are disclosed of formula (I): ##STR1## wherein R.sub.1 represents R.sub.5 R.sub.6 NCOCH.sub.2 --, R.sub.5 CONH(CH.sub.2).sub.p --,R.sub.5 R.sub.6 NSO.sub.2 (CH.sub.2).sub.p -- or R.sub.7 SO.sub.2 NH(CH.sub.2).sub.p --, (where R.sub.5 and R.sub.6 each represents a hydrogen atom or a C.sub.1-3 alkyl group, R.sub.7 represents C.sub.1-3 alkyl and p is zero or one),R.sub.2 is hydrogen or C.sub.1-3 alkyl;R.sub.3 and R.sub.4 each represents hydrogen atom, C.sub.1-3 alkyl, or 2-propenyl;m is zero or an integer from 1 to 4; andn is an integer from 2 to 5; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. They may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers of excipients for administration by any convenient route.Various methods for the preparation of the compounds (I) are disclosed.

摘要翻译： 公开了式（I）的吲哚：其中R1表示R5R6NCOCH2-，R5CONH（CH2）p-，R5R6NSO2（CH2）p-或R7SO2NH（CH2）p-，（其中R5和R6各自表示 氢原子或C 1-3烷基，R 7表示C 1-3烷基，p为0或1），R 2为氢或C 1-3烷基; R3和R4各自表示氢原子，C1-3烷基或2-丙烯基; m为0或1至4的整数; n为2〜5的整数。 和其生理上可接受的盐和溶剂合物（例如水合物）。 这些化合物具有有效和选择性的血管收缩剂活性，并被用于治疗偏头痛。 它们可以配制成具有药学上可接受的赋形剂载体的药物组合物，用于通过任何方便的途径给药。 公开了制备化合物（I）的各种方法。

公开(公告)号：US5276050A

公开(公告)日：1994-01-04

申请号：US908329

申请日：1992-07-06

申请人： Steven J. Cooper ,  Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North

发明人： Steven J. Cooper ,  Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North

IPC分类号： A61K31/415

CPC分类号： A61K31/415

摘要： The invention relates to the use of compounds of the general formula (I) ##STR1## and physiologically acceptable salts and solvates thereof, in which Im represents an imidazolyl group of formula: ##STR2## and R.sup.1 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, phenyl, phenylC.sub.1-3 alkyl, phenylmethoxymethyl, phenoxyethyl, phenoxymethyl, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 or --SO.sub.2 R.sup.5 (wherein R.sup.5 and R.sup.6, which may be the same or different each represents a hydrogen atom, a C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl group, or a phenyl or phenylC.sub.1-4 alkyl group, in which the phenyl group is optionally substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, with the proviso that R.sup.5 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.5 or --SO.sub.2 R.sup.5);one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phenylC.sub.1-3 alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;and n represents 2 or 3,for the treatment of a condition involving excessive eating, for example bulimia.

摘要翻译： 本发明涉及通式（I）化合物（Ⅰ）及其生理上可接受的盐和溶剂化物，其中Im表示下式的咪唑基：其中R1表示 氢原子或选自C 1-6烷基，C 3-6烯基，C 3-10炔基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，苯基，苯基C 1-3烷基，苯基甲氧基甲基，苯氧基乙基，苯氧基甲基，-CO 2 R 5，-COR 5，-CONR 5 R 6或 -SO 2 R 5（其中R 5和R 6可以相同或不同，各自表示氢原子，C 1-6烷基或C 3-7环烷基或苯基或苯基C 1-4烷基，其中苯基任选被一个 或更多C 1-4烷基，C 1-4烷氧基或羟基或卤素原子，条件是当R 1表示-CO 2 R 5或-SO 2 R 5基团时，R 5不表示氢原子）; 由R 2，R 3和R 4表示的基团之一是氢原子或C 1-6烷基，C 3-7环烷基，C 3-6烯基，苯基或苯基C 1-3烷基，其它两个基团可以相同或 不同的是氢原子或C1-6烷基; n表示2或3，用于治疗涉及过度饮食的病症，例如贪食症。

公开(公告)号：US5066660A

公开(公告)日：1991-11-19

申请号：US570513

申请日：1990-08-21

申请人： Alexander W. Oxford ,  Ian H. Coates ,  Darko Butina

发明人： Alexander W. Oxford ,  Ian H. Coates ,  Darko Butina

IPC分类号： A61K31/4427 ,  A61K31/445 ,  A61P25/04 ,  A61P25/06 ,  C07D401/04

CPC分类号： C07D401/04

摘要： Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents H or C.sub.1-6 alkyl;R.sub.2 represents H, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, phenyl or phen(C.sub.1-3)alkyl in which the phenyl ring is optionally substituted by halogen, C.sub.1-4 alkoxy, hydroxy or C.sub.1-3 alkyl;R.sub.3 represents H, C.sub.1-3 alkyl, --CO.sub.2 R.sub.5, --COR.sub.5, --COCO.sub.2 R.sub.5 or --CONHR.sub.5 whereR.sub.5 represents H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-4 alkenyl, aryl or ar(C.sub.1-4)alkyl in which the aryl group is optionally substituted by halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl or hydroxy) (provided that where R.sub.3 represents --CO.sub.2 R.sub.5, R.sub.5 is other than H);R.sub.4 represents H, C.sub.1-3 alkyl, C.sub.3-6 alkenyl, phenyl or phen (C.sub.1-3)alkyl;A-B represents CH--CH.sub.2 --or C.dbd.CH--D represents --CO-- or --SO.sub.2 --n represents 0, 1-5;provided that when D represents --SO.sub.2, n is 2, R.sub.3 represents H and R.sub.4 represents H or C.sub.1-3 alkyl, R.sub.2 is other than H or C.sub.1-6 alkyl; and pharmaceutically acceptable salts and solvates (for example hydrates) thereof.The compounds are indicated as useful for the treatment of migraine, cluster headache, chronic paroxysmal hemicrania and headache associated with vascular disorders.Processes and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.