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：US4859662A

公开(公告)日：1989-08-22

申请号：US281031

申请日：1988-12-07

申请人： Ian H. Coates ,  John Bradshaw ,  James A. Bell ,  David C. Humber ,  George B. Ewan ,  William L. Mitchell ,  Barry J. Price

发明人： Ian H. Coates ,  John Bradshaw ,  James A. Bell ,  David C. Humber ,  George B. Ewan ,  William L. Mitchell ,  Barry J. Price

IPC分类号： C07D403/06

CPC分类号： C07D403/06

摘要： The invention relates to compounds of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## and the various substituents are defined hereinbelow. The compounds 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： 本发明涉及通式（I）的化合物：其中Im表示下式的咪唑基：其中各种取代基如下所定义。 这些化合物是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。

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：US5578628A

公开(公告)日：1996-11-26

申请号：US501974

申请日：1990-03-30

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 ,  A61K31/4178

CPC分类号： A61K31/4178 ,  A61K31/415 ,  Y10S514/966

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.-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 cycloalkynyl, 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.

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 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环炔基，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。

公开(公告)号：US4929632A

公开(公告)日：1990-05-29

申请号：US177042

申请日：1988-04-04

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 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.

公开(公告)号：US4695578A

公开(公告)日：1987-09-22

申请号：US931032

申请日：1986-11-17

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： C07D209/88 ,  C07D403/06 ,  C07D521/00 ,  A61K31/415

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

摘要： The invention relates to compounds of formula (I). ##STR1## wherein R.sub.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, C.sub.3-7 cycloalkyl-(C.sub.1-4) alkyl, 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, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates, e.g. hydrates thereof.The compounds are potent selective antagonists at "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of migraine and psychotic disorders such as schizophrenia.

摘要翻译： 本发明涉及式（I）化合物。 （I）其中R1表示氢原子或C1-10烷基，C3-7环烷基，C3-6烯基，C3-7环烷基 - （C1-4）烷基，C3-10炔基，苯基或苯基 - C 1-3烷基，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， 可以相同或不同的另外两个基团表示氢原子或C 1-6烷基; 和生理上可接受的盐和溶剂合物，例如 其水合物。 这些化合物是“神经元”5-羟色胺受体的有效选择性拮抗剂，可用于治疗偏头痛和精神病性疾病如精神分裂症。

公开(公告)号：US4822881A

公开(公告)日：1989-04-18

申请号：US126202

申请日：1987-11-27

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

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

IPC分类号： A61K31/415 ,  C07D403/06

CPC分类号： C07D403/06

摘要： The invention relates to compounds of the general formula (I): ##STR1## wherein Im represents an imidazolyl group of the formula: ##STR2## and the various substituents are defined hereinbelow. The compounds 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： 本发明涉及通式（I）的化合物：其中Im表示下式的咪唑基：其中各种取代基如下所定义。 这些化合物是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。

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.