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。

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：US4352798A

公开(公告)日：1982-10-05

申请号：US283429

申请日：1981-07-15

申请人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

发明人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

IPC分类号： C07J41/00 ,  C07J63/00 ,  A61K31/56

CPC分类号： C07J63/008 ,  C07J41/0005 ,  C07J41/0011 ,  Y10S514/821

摘要： Compounds of formula ##STR1## (wherein): R.sup.1 is a hydrogen atom, a C.sub.1-8 alkyl group or a C.sub.3-7 cycloalkyl group; andR.sup.2 is a hydrogen atom, a C.sub.1-6 alkyl group or a C.sub.3-6 cycloalkyl group; and the D-homo analogues thereof having the group --CO.sub.2 R.sup.2 (wherein R.sup.2 is as defined above) at the 17a.beta.-position and salts and zwitterionic forms thereof have activity as antidysrhythmic agents and may be applicable for treatment of ventricular dysrhythmias in humans or animals. The compounds may be provided in the form of compositions in admixture with pharmaceutical carriers and excipients and may be prepared by a variety of processes known for producing steroids of this type.

摘要翻译： 式（I）（I）的化合物：其中：R 1是氢原子，C 1-8烷基或C 3-7环烷基; R2为氢原子，C1-6烷基或C3-6环烷基; 并且其在17aβ位具有-CO 2 R 2基团（其中R 2如上所定义）的D-均一类似物及其盐和两性离子形式具有作为抗心律不齐剂的活性，并且可用于治疗人或动物中的室性心律失常 。 化合物可以以与药物载体和赋形剂混合的组合物的形式提供，并且可以通过已知用于生产这种类固醇的各种方法制备。

公开(公告)号：US4515786A

公开(公告)日：1985-05-07

申请号：US509667

申请日：1983-06-30

申请人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

发明人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

IPC分类号： A61K31/56 ,  A61P9/06 ,  C07J41/00 ,  C07J63/00 ,  C07J3/00

CPC分类号： C07J63/008 ,  C07J41/0005 ,  C07J41/0011

摘要： R.sup.3 is a C.sub.1-6 alkyl group or a C.sub.3-7 cycloalkyl group; andR.sup.4 is a group --OR.sup.5 or --OCOR.sup.6 whereR.sup.5 is an optionally substituted alkyl or alkenyl group which may contain up to 6 carbon atoms, an optionally substituted C.sub.3-7 cycloalkyl group, a phenyl group or a carbon-attached 5-7 membered heterocyclic ring in which the hetero-atom is selected from nitrogen, oxygen and sulphur, andR.sup.6 is a hydrogen atom or a group R.sup.5 as defined above;provided that when the compounds contain a 5.beta.-hydrogen atom, R.sup.2 is a hydrogen atom and salts thereof, which compounds have activity as antidysthythmic agents.

摘要翻译： （I）其中R1是C1-8烷基或C3-7环烷基; R2是氢原子，C1-6烷氧基或C2-5烷酰氧基; R3是C1-6烷基或C3-7环烷基; 并且R 4是基团-OR 5或-OCOR 6，其中R 5是可以含有至多6个碳原子的任选取代的烷基或烯基，任选取代的C 3-7环烷基，苯基或连接碳的5-7元 杂环选自氮，氧和硫，R6是氢原子或如上定义的基团R5; 条件是当化合物含有5个β-氢原子时，R2是氢原子及其盐，该化合物具有作为抗心律失常药的作用。

公开(公告)号：US4497805A

公开(公告)日：1985-02-05

申请号：US475899

申请日：1983-03-16

申请人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber ,  Anthony J. Pateman

发明人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber ,  Anthony J. Pateman

IPC分类号： A61K31/56 ,  A61P9/06 ,  C07J41/00 ,  C07J63/00 ,  C07J71/00 ,  A01N45/00 ,  C07J3/00

CPC分类号： C07J41/0011 ,  C07J41/0005 ,  C07J63/008 ,  C07J71/001

摘要： Compounds of the formula ##STR1## wherein R.sup.1 is a C.sub.1-8 alkyl group or a C.sub.3-7 cycloalkyl group;R.sup.2 is a C.sub.1-6 alkyl group or a C.sub.3-7 cycloalkyl group;R.sup.3 is a hydroxy group or a group of formula --OR.sup.4 or --OCOR.sup.5 whereR.sup.4 is an alkyl or alkenyl group which may contain up to 6 carbon atoms (or such a group substituted by halogen, C.sub.1-6 alkoxy, carboxyl, phenyl, phenyl substituted by nitro, halo, C.sub.1-4 alkoxy or C.sub.1-4 alkyl), a C.sub.3-7 cycloalkyl group, a phenyl group (or such a group substituted by nitro, halo, C.sub.1-4 alkoxy or C.sub.1-4 alkyl), or a carbon-attached 5-7 membered heterocyclic ring in which the hetero atom is selected from nitrogen, oxygen and sulphur, andR.sup.5 is a hydrogen atom or a group R.sup.4 as defined above;and the D-homo analogues thereof having the group --CO.sub.2 R.sup.2 (wherein R.sup.2 is as defined above) at the 17a.beta.-position, and salts thereof have activity as antidysrhythmic agents and may be applicable for the treatment of dysrhthmias in humans or animals. The compounds may be provided in the form of compositions in admixture with pharmaceutical carriers or excipients and may be prepared by a variety of processes known for producing steroids of this type. The invention also provides intermediates for the preparation of compounds of formula (I), in which intermediates R.sup.1 and/or R.sup.2 is replaced by a hydrogen atom, and processes for the preparation of such intermediates.

摘要翻译： 式（I）的化合物，其中R 1是C 1-8烷基或C 3-7环烷基; R2是C1-6烷基或C3-7环烷基; R3是羟基或式-OR4或-OCOR5的基团，其中R4是可以含有至多6个碳原子的烷基或烯基（或这种被卤素，C 1-6烷氧基，羧基，苯基，苯基 被硝基，卤素，C 1-4烷氧基或C 1-4烷基取代），C 3-7环烷基，苯基（或被硝基，卤素，C 1-4烷氧基或C 1-4烷基取代的基团），或 碳杂环的5-7元杂环，其中杂原子选自氮，氧和硫，R5是氢原子或如上所定义的基团R 4; 和其在17aβ位具有-CO 2 R 2基团（其中R 2如上所定义）的D-均一类似物及其盐具有作为抗心律失常药物的活性，并且可用于治疗人或动物中的dysrhthmias。 化合物可以以与药物载体或赋形剂混合的组合物的形式提供，并且可以通过已知用于生产这种类固醇的各种方法制备。 本发明还提供用于制备式（I）化合物的中间体，其中中间体R1和/或R2被氢原子代替，以及制备这种中间体的方法。

公开(公告)号：US4353898A

公开(公告)日：1982-10-12

申请号：US283454

申请日：1981-07-15

申请人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

发明人： Gordon H. Phillipps ,  David C. Humber ,  George B. Ewan ,  Barry A. Coomber

IPC分类号： A61K31/56 ,  A61P9/06 ,  C07J41/00 ,  C07J63/00

CPC分类号： C07J63/008 ,  C07J41/0005 ,  C07J41/0011 ,  C07J63/00 ,  Y10S514/821

摘要： Compounds of formula ##STR1## wherein: R.sup.1 is a C.sub.1-8 alkyl group or a C.sub.3-7 cycloalkyl group;R.sup.2 is a hydrogen atom, a C.sub.1-6 alkoxy group or a C.sub.2-5 alkanoyloxy group; andR is a C.sub.1-8 alkyl group or a C.sub.3-7 cycloalkyl group;provided that when the compounds contain a 5.beta.-hydrogen atom, R.sup.2 is a hydrogen atom, and the D-homo analogues thereof having the group --CO.sub.2 R.sup.3 (wherein R.sup.3 is as defined above) at the 17a.beta.-position, and salts thereof have activity as antidysrhythmic agents and may be applicable for treatment of ventricular dysrhythmias in humans or animals. The compounds may be provided in the form of compositions in admixture with pharmaceutical carriers and excipients and may be prepared by a variety of processes known for producing steroids of this type. The invention also provides intermediates for the preparation of the compounds of formula (I), wherein R.sup.3 and/or R.sup.1 are replaced with hydrogen atoms, and processes for the preparation of such intermediates.

摘要翻译： 式（I）的化合物其中：R1是C1-8烷基或C3-7环烷基; R2是氢原子，C1-6烷氧基或C2-5烷酰氧基; 并且R是C 1-8烷基或C 3-7环烷基; 条件是当化合物含有5β-氢原子时，R 2是氢原子，并且在17β-位具有-CO 2 R 3基团（其中R 3如上定义）的D-均一类似物及其盐具有 作为抗心律失常药物的活性，可用于治疗人或动物的心室心律失常。 化合物可以以与药物载体和赋形剂混合的组合物的形式提供，并且可以通过已知用于生产这种类固醇的各种方法制备。 本发明还提供制备式（I）化合物的中间体，其中R 3和/或R 1被氢原子取代，以及制备这种中间体的方法。

公开(公告)号：US5166136A

公开(公告)日：1992-11-24

申请号：US384685

申请日：1989-07-25

申请人： Peter Ward ,  George B. Ewan

发明人： Peter Ward ,  George B. Ewan

IPC分类号： A61K31/40 ,  A61K31/435 ,  A61K38/00 ,  A61P11/00 ,  A61P25/04 ,  A61P25/18 ,  A61P29/00 ,  A61P31/04 ,  A61P43/00 ,  C07D471/10 ,  C07D487/10 ,  C07K7/06 ,  C07K7/22

CPC分类号： C07D471/10 ,  C07D487/10 ,  C07K7/06 ,  C07K7/22 ,  A61K38/00 ,  Y02P20/55

摘要： These are described spirolactam derivatives of formulae (Ia) and (Ib) ##STR1## wherein R represents a hydrogen atom or a conventional nitrogen protecting group;R.sup.1 represents a hydrogen atom or a conventional carboxyl protecting group or activating group;R.sup.2 represents the side chain of any naturally occurring amino acid;m represents 1 or 2;n represents 1 or 2;the confirguration at * may be (R) or (S) or a mixture thereof; with the proviso that when R represents the nitrogen protecting group R.sup.3 --CO(O)-- (where R.sup.3 represents (CH.sub.3).sub.3 C--), the group --CO.sub.2 R.sup.1 represents the protected carboxy group --CO.sub.2 CH.sub.3, m is 1 and n is 1 in the compounds of formula (Ib); R.sup.2 may not represent an arylmethyl group;and solvates or acid addition salts thereof.These derivatives are of value in the preparation of spirolactam compounds which, depending on their stereochemistry, are either antagonists or agonists of substance P, and as such have a variety of therapeutic properties.

公开(公告)号：US4197296A

公开(公告)日：1980-04-08

申请号：US946087

申请日：1978-09-26

申请人： Gordon H. Phillipps ,  George B. Ewan

发明人： Gordon H. Phillipps ,  George B. Ewan

IPC分类号： C07J1/00 ,  C07J13/00 ,  C07J21/00 ,  C07J41/00 ,  C07J71/00 ,  C07J7/00 ,  A61K31/58

CPC分类号： C07J41/0016 ,  C07J1/0011 ,  C07J13/007 ,  C07J21/008 ,  C07J41/0011 ,  C07J41/005 ,  C07J71/001

摘要： Steroids of the androstane series are described which possess a 3.alpha.-hydroxy group, a 5.alpha.- or 5.beta.- hydrogen atom, a 10- methyl group, an 11.alpha.- substituted amino group. The 17-position may be unsubstituted or substituted by a methyl or ethyl group in the .beta.-configuration or by an oxo group, or there may be a 16.beta., 17.beta.-epoxide group. A 2.beta.-alkoxy group may optionally be present.The compounds, particularly their salts, have anaesthetic activity.

摘要翻译： 描述了具有3α-羟基，5α或5β-氢原子，10-甲基，11α-取代的氨基的雄甾烷系列的类固醇。 17位可以是未取代的或被β-构型中的甲基或乙基取代，或被氧代基取代，或者可以是16β，17β-环氧基。 可以任选地存在2个β-烷氧基。 化合物，特别是它们的盐具有麻醉活性。