公开(公告)号：US4894387A

公开(公告)日：1990-01-16

申请号：US030235

申请日：1987-03-26

申请人： Darko Butina ,  Michael D. Dowle ,  Ian H. Coates

发明人： Darko Butina ,  Michael D. Dowle ,  Ian H. Coates

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07C67/00 ,  C07C301/00 ,  C07C311/35 ,  C07D209/16 ,  C07D209/18

CPC分类号： C07D209/18 ,  C07D209/16

摘要： Compounds are disclosed of the general formula (I) ##STR1## wherein R.sub.1 represents halogen, alkyl, alkoxy or hydroxyl, or a group NR.sub.a R.sub.b or CON.sub.a R.sub.b, where R.sub.a and R.sub.b are hydrogen, alkyl or alkenyl or with the nitrogen atom form a saturated monocyclic 5 to 7-membered ring;R.sub.2 represents hydrogen or alkyl;R.sub.3 and R.sub.4 represent hydrogen, C.sub.1-3 alkyl or propenyl or R.sub.3 and R.sub.4 together form an aralkylidene group; Alk represents a C.sub.2-3 alkylene chain;n and m, are integers of 1 to 4 or n is zero, and their physiologically acceptable salts and solvates.The compounds are described as useful in treating pain originating from dilatation of the cranial vasculature in particular migraine and cluster headache and can be formulated in conventional manner as pharmaceutical compositions with carriers or excipients for administration by any convenient route.

摘要翻译： 公开了通式（I）的化合物其中R 1表示卤素，烷基，烷氧基或羟基，或NRaRb或CONaRb基团，其中R a和R b是氢，烷基或链烯基或氮原子形式 饱和单环5至7元环; R2代表氢或烷基; R3和R4代表氢，C1-3烷基或丙烯基或R3和R4一起形成亚烷基; Alk表示C2-3亚烷基链; n和m是1〜4的整数或n为0的整数，以及它们的生理上可接受的盐和溶剂合物。 描述了这些化合物可用于治疗源于颅血管扩张的疼痛，特别是偏头痛和丛集性头痛，并且可以以常规方式配制成具有载体或赋形剂的药物组合物，通过任何方便的途径给药。

公开(公告)号：US4753789A

公开(公告)日：1988-06-28

申请号：US877805

申请日：1986-06-24

申请人： Michael B. Tyers ,  Ian H. Coates ,  David C. Humber ,  George B. Ewan ,  James A. Bell

发明人： Michael B. Tyers ,  Ian H. Coates ,  David C. Humber ,  George B. Ewan ,  James A. Bell

IPC分类号： C07D403/06 ,  A61K31/415 ,  A61P1/00 ,  A61P1/08

CPC分类号： A61K31/415 ,  Y10S514/872 ,  Y10S514/917 ,  Y10S514/922

摘要： The invention relates to the use of compounds of the 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 cycoalkyl-(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 byR.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, represents a hydrogen atom or a C.sub.1-6 alkyl group;and physiologically acceptable salts and solvates thereof, for the relief of nausea and vomiting and/or the promotion of gastric emptying and for the manufacture of a medicament for this purpose. Promotion of gastric emptying may be for the relief of gastro-intestinal disorders associated with gastric stasis or may be of advantage of radiological examination procedures.The invention also relates to a product containing a therapeutic agent liable to induce nausea and vomiting, e.g. a cytostatic agent such as a cyclophosphamide, an alkylating agent or a platinum complex, and a compound of the general formula (I) as a combined preparation for simultaneous separate or sequential use in therapy.

公开(公告)号：US4749718A

公开(公告)日：1988-06-07

申请号：US888257

申请日：1986-07-23

申请人： Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

发明人： Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

IPC分类号： A61K31/415 ,  A61P1/04 ,  A61P1/08 ,  A61P25/00 ,  A61P25/04 ,  A61P43/00 ,  C07D209/88 ,  C07D403/06 ,  C07D521/00 ,  A61K31/40

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

摘要： The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 represents a group 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 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.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);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, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates thereof.The compounds are potent and selective antagonists of "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; pain; gastric stasis; symptoms of gastrointestinal dysfunction such as occur with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence; migraine; and nausea and vomiting.

摘要翻译： 本发明涉及通式（I）的化合物：其中R 1表示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，各自代表氢原子 ，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烷氧基或羟基取代 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 2-6烯基或苯基 - （C 1-3）烷基，其它两个基团， 可以相同或不同，表示氢原子或C1-6烷基; 及其生理上可接受的盐和溶剂合物。 这些化合物是“神经元”5-羟色胺受体的有效和选择性拮抗剂，可用于治疗精神病（如精神分裂症和躁狂症）; 焦虑; 疼痛; 胃潴留; 胃肠功能障碍的症状如消化不良，消化性溃疡，反流性食管炎和胃肠气胀等发生; 偏头痛 和恶心呕吐。

公开(公告)号：US4725615A

公开(公告)日：1988-02-16

申请号：US888258

申请日：1986-07-23

申请人： Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

发明人： Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

IPC分类号： A61K31/415 ,  A61P1/04 ,  A61P1/08 ,  A61P25/00 ,  A61P25/04 ,  A61P43/00 ,  C07D209/88 ,  C07D403/06 ,  C07D521/00 ,  A61K31/40 ,  C07D401/06

CPC分类号： C07D231/12 ,  C07D209/88 ,  C07D233/56 ,  C07D249/08 ,  C07D403/06

摘要： The invention relates to compounds of the 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;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, represents a hydrogen atom or a C.sub.1-6 alkyl group; and X represents 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.5 R.sup.6 or CONR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6, 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 physiologically acceptable salts and solvates thereof.The compounds are potent and selective antagonists of "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania;); anxiety, pain; gastric stasis; symptoms of gastrointestinal dysfunction such as occur with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence; migraine; and nausea and vomiting.

摘要翻译： 本发明涉及通式（I）的化合物：其中R 1表示氢原子或C 1-10烷基，C 3-7环烷基，C 3-7环烷基 - （C 1-4） - 烷基，C 3 -6-烯基，C 3-10炔基，苯基或苯基 - （C 1-3）烷基; 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）烷基和其它两个基团，其中 可以相同或不同，表示氢原子或C1-6烷基; 并且X表示卤原子或羟基，C 1-4烷氧基，苯基 - （C 1-3） - 烷氧基或C 1-6烷基或NR 5 R 6或CONR 5 R 6基团，其中R 5和R 6可各自相同或不同 表示氢原子或C1-4烷基或C3-4烯基，或与它们所连接的氮原子一起形成饱和的5至7元环; 及其生理上可接受的盐和溶剂合物。 这些化合物是“神经元”5-羟色胺受体的有效和选择性拮抗剂，可用于治疗精神病（如精神分裂症和躁狂症）; 焦虑，痛苦; 胃潴留; 胃肠功能障碍的症状如消化不良，消化性溃疡，反流性食管炎和胃肠气胀等发生; 偏头痛 和恶心呕吐。

公开(公告)号：US5240954A

公开(公告)日：1993-08-31

申请号：US804020

申请日：1991-12-09

申请人： Michael B. Tyers ,  Ian H. Coates ,  David C. Humber ,  George B. Ewan ,  James A. Bell

发明人： Michael B. Tyers ,  Ian H. Coates ,  David C. Humber ,  George B. Ewan ,  James A. Bell

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## 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 byR.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, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates thereof, for the relief of nausea and vomiting and/or the promotion of gastric emptying and for the manufacture of a medicament for this purpose. Promotion of gastric emptying may be for the relief of gastro-intestinal disorders associated with gastric stasis or may be of advantage in radiological examination procedures.The invention also relates to a product containing a therapeutic agent liable to induce nausea and vomiting, e.g. a cytostatic agent such as a cyclophosphamide, an alkylating agent or a platinum complex, and a compound of the general formula (I) as a combined preparation for simultaneous separate or sequential use in therapy.

摘要翻译： 本发明涉及通式（I）化合物其中R 1表示氢原子或C 1-10烷基，C 3-7环烷基，C 3-7环烷基 - （C 1-4）烷基 C 3-6烯基，C 3-10炔基，苯基或苯基-C 1-3烷基; 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，其它两个基团可以是 相同或不同，表示氢原子或C 1-6烷基; 及其生理上可接受的盐和溶剂化物，用于缓解恶心和呕吐和/或促进胃排空和用于制造用于此目的的药物。 促进胃排空可能是为了缓解与胃潴留相关的胃肠道疾病，或者在放射学检查程序中可能是有利的。 本发明还涉及含有易诱发恶心和呕吐的治疗剂的产品，例如， 细胞生长抑制剂如环磷酰胺，烷化剂或铂络合物，以及通式（I）的化合物作为用于在治疗中同时分开或顺次使用的组合制剂。

公开(公告)号：US4957609A

公开(公告)日：1990-09-18

申请号：US312172

申请日：1989-02-21

申请人： Neil Godfrey ,  Ian H. Coates ,  James A. Bell ,  David C. Humber ,  George B. Ewan

发明人： Neil Godfrey ,  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

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

摘要： The invention relates to a process for the preparation of compounds 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-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; or a salt or protected derivative thereof by cyclization of a compound of general formula (II) ##STR2## wherein X represents a hydrogen atom or a halogen atom and 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： 本发明涉及制备通式（I）化合物的方法，其中R 1表示氢原子或C 1-10烷基，C 3-7环烷基，C 3-7环烷基 - （C 1-4） ）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， 7个环烷基，C 2-6烯基或苯基 - 苯基 - （C 1-3）烷基，其它两个可以相同或不同的基团表示氢原子或C1-6烷基; 或其盐或其保护的衍生物通过环化通式（II）的化合物其中X表示氢原子或卤素原子，并且R 1，R 2，R 3和R 4如上所定义，或其盐 或其受保护的衍生物。 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：US4816470A

公开(公告)日：1989-03-28

申请号：US789831

申请日：1985-11-15

申请人： Michael D. Dowle ,  Ian H. Coates

发明人： Michael D. Dowle ,  Ian H. Coates

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  A61P25/06 ,  C07D209/10 ,  C07D209/16 ,  C07D209/18 ,  C07D209/24 ,  C07D209/48

CPC分类号： C07D209/48 ,  C07D209/10 ,  C07D209/16 ,  C07D209/18 ,  C07D209/24

摘要： Indole derivatives of the general formula (I) are disclosed: ##STR1## where R.sub.1 is H or an alkyl or alkenyl group, R.sub.2 is H, or an alkyl, alkenyl, aryl, aralkyl or cycloalkyl group;R.sub.3 is H or an alkyl group;R.sub.4 and R.sub.5 are independently H or an alkyl or propenyl group or together form an aralkylidene group; andAlk is an optionally substituted alkylene chain; and their physiologically acceptable salts and solutes.These compounds are potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner.Various methods for the production of the compounds are disclosed including a Fischer-indole cyclization process.

摘要翻译： 公开了通式（I）的吲哚衍生物：其中R 1是H或烷基或烯基，R 2是H或烷基，烯基，芳基，芳烷基或环烷基; R3是H或烷基; R 4和R 5独立地为H或烷基或丙烯基或一起形成亚烷基; 并且Alk是任选取代的亚烷基链; 及其生理上可接受的盐和溶质。 这些化合物潜在地可用于治疗偏头痛，并且可以以常规方式配制成药物组合物。 公开了制备化合物的各种方法，包括费 - 吲哚环化方法。

公开(公告)号：US4814344A

公开(公告)日：1989-03-21

申请号：US103645

申请日：1987-10-02

申请人： David C. Humber ,  Ian H. Coates ,  James A. Bell ,  George B. Ewan

发明人： David C. Humber ,  Ian H. Coates ,  James A. Bell ,  George B. Ewan

IPC分类号： C07D209/12 ,  A61K31/415 ,  A61P43/00 ,  C07D403/06 ,  C07D521/00 ,  C07D403/14

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

摘要： The invention relates to compounds of formula (I) ##STR1## wherein R.sup.1 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, or phenyl C.sub.1-3 alkyl, --CO.sub.2 R.sup.10, --COR.sup.10, --CONR.sup.10 R.sup.11 or --SO.sub.2 R.sup.10 (wherein R.sup.10 and R.sup.11, 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.10 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.10 or --SO.sub.2 R.sup.10);R.sub.2 represents a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-7 cycloalkyl, phenyl or phenyl C.sub.1-3 alkyl group;R.sub.3 and R.sub.4, which may be the same or different, each represents a hydrogen atom or a C.sub.1-6 alkyl group;One of the groups represented by R.sup.5, R.sup.6 and R.sup.7 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.1-6 hydroxyalkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 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; andQ represents a hydrogen or 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.8 R.sup.9 or --CONR.sup.8 R.sup.9 wherein R.sup.8 and R.sup.9, 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 physiologically acceptable salts and solvates thereof.The comopounds are potent and selective antagonists of the effect of 5-HT at 5-HT.sub.3 receptors and are useful, for example, in the treatment of psychotic disorders, anxiety, and nausea and vomiting.

摘要翻译： 本发明涉及式（I）化合物其中R 1表示氢原子或选自C 1-10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，苯基或苯基C 1-3烷基，-CO 2 R 10，-COR 10，-CONR 10 R 11或-SO 2 R 10（其中R 10和R 11可以相同或不同，各自表示氢原子，C1-6 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取代，条件是 当R 1表示-CO 2 R 10或-SO 2 R 10基团时，R 10不表示氢原子; R 2表示氢原子或C 1-6烷基，C 3-6烯基，C 3-7环烷基，苯基或苯基C 1-3烷基; R 3和R 4可以相同或不同，各自表示氢原子或C 1-6烷基; 由R5，R6和R7表示的基团之一是氢原子或C1-6烷基，C1-6羟基烷基，C3-7环烷基，C2-6烯基，苯基或苯基C1-3烷基， 其它两个可以相同或不同的基团表示氢原子或C1-6烷基; 和Q表示氢或卤素原子，或羟基，C 1-4烷氧基，苯基C 1-3烷氧基或C 1-6烷基或-NR 8 R 9或-CONR 8 R 9，其中R 8和R 9可以相同或不同 各自表示氢原子或C1-4烷基或C3-4烯基，或与它们所连接的氮原子一起形成饱和的5至7元环; 及其生理上可接受的盐和溶剂合物。 组合物是5-HT在5-HT 3受体上的作用的有效和选择性拮抗剂，可用于治疗精神病，焦虑和恶心和呕吐。