公开(公告)号：US4264614A

公开(公告)日：1981-04-28

申请号：US95065

申请日：1979-11-16

申请人： John W. Clitherow ,  Barry J. Price ,  John Bradshaw

发明人： John W. Clitherow ,  Barry J. Price ,  John Bradshaw

IPC分类号： A61K31/155 ,  A61K31/335 ,  A61K31/38 ,  A61P1/00 ,  C07C67/00 ,  C07C209/00 ,  C07C211/27 ,  C07C213/00 ,  C07C217/48 ,  C07C239/00 ,  C07C275/12 ,  C07C279/04 ,  C07C279/28 ,  C07C301/00 ,  C07C311/64 ,  C07C325/00 ,  C07C335/08 ,  C07D233/64 ,  C07D295/096 ,  C07D307/38 ,  C07D307/42 ,  C07D307/52 ,  C07D333/14 ,  A61K31/34 ,  C07D307/68 ,  C07D333/38

CPC分类号： C07D295/096 ,  C07C279/28 ,  C07D307/38 ,  C07D307/42 ,  C07D307/52 ,  C07D333/14 ,  Y10S514/886 ,  Y10S514/926 ,  Y10S514/927

摘要： The invention provides compounds of general formula ##STR1## and physiologically acceptable salts, hydrates and bioprecursors thereof, in whichY and Z, which may be the same or different, each represent oxygen, sulphur, =CHNO.sub.2 or =NR.sub.3 where R.sub.3 is hydrogen, nitro, cyano, lower alkyl, aryl, alkylsulphonyl or arylsulphonyl;p has a value from 2 to 12;R.sub.1 represents ##STR2## in which R.sub.4 and R.sub.5 which may be the same or different, each represent hydrogen, lower alkyl, cycloalkyl, lower alkenyl, aralkyl or lower alkyl interrupted by an oxygen atom or a group >N-R.sub.6 in which R.sub.6 represents hydrogen or lower alkyl, or R.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a 5 to 7-membered saturated heterocyclic ring which may contain an additional oxygen atom or the group >NR.sub.6 ;Q represents a furan or thiophen ring in which incorporation into the rest of the molecule is through bonds at the 2 and 5 positions, or a benzene ring in which incorporation into the rest of the molecule is through bonds at the 1 and 3 or 1 and 4 positions;X represents --CH.sub.2 --, --O-- or --S--;n represents zero or 1;m represents 2, 3 or 4 andAlk represents a straight chain alkylenegroup of 1 to 3 carbon atoms;and R.sub.2 represents lower alkyl or the group--(CH.sub.2).sub.y E(CH.sub.2).sub.x Gin whichY represents 2, 3 or 4 or can additionallyrepresent zero or 1 when E is a --CH.sub.2 -- group;x represents zero, 1 or 2;E represents --CH.sub.2 --, --0-- or --S--; andG represents a monocyclic 5 or 6 membered carbocyclic or heterocyclic aromatic ring, or G represents the group ##STR3## where Q' represents any of the rings defined for Q;Alk' represents any of the groups defined for Alk;and R.sub.4 ' and R.sub.5 ' which may be the same or different represent any of the groups defined for R.sub.4 or R.sub.5.The compounds of formula (I) have pharmacological activity as selective histamine H.sub.2 -antagonists.

摘要翻译： 本发明提供了通式（I）的化合物及其生理上可接受的盐，水合物和生物前体，其中Y和Z可以相同或不同，各自表示氧，硫，= CHNO 2或= NR 3，其中R 3 是氢，硝基，氰基，低级烷基，芳基，烷基磺酰基或芳基磺酰基; p的值为2到12; R 1表示其中可以相同或不同的R 4和R 5各自表示氢，低级烷基，环烷基，低级烯基，芳烷基或被氧原子间隔的低级烷基或基团> N-R6，其中R 6表示 氢或低级烷基，或R4和R5与它们所连接的氮原子一起形成可含有另外的氧原子或基团> NR 6的5至7元饱和杂环; Q表示呋喃或噻吩环，其中与分子的其余部分结合通过2和5位的键，或苯环，其中结合到分子的其余部分通过1和3或1的键和 4个职位; X表示-CH 2 - ， - O-或-S-; n表示0或1; m表示2,3或4，Alk表示1〜3个碳原子的直链亚烷基; 并且R 2表示低级烷基或基团 - （CH 2）y E（CH 2）x G，其中Y表示2,3或4，或者当E是-CH 2 - 基时，可以另外表示0或1; x表示零，1或2; E表示-CH 2 - ， - O-或-S-; 并且G表示单环5或6元碳环或杂环芳环，或G表示基团，其中Q'表示为Q定义的任何环; Alk'代表为Alk定义的任何组; 和可以相同或不同的R 4'和R 5'表示对于R 4或R 5定义的任何基团。 式（I）化合物具有作为选择性组胺H2拮抗剂的药理学活性。

公开(公告)号：US5202343A

公开(公告)日：1993-04-13

申请号：US887607

申请日：1992-05-22

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## 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, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 or --SO.sub.2 R.sup.5 ;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;Q represents a hydrogen or a halogen atom, or a hydroxy, C.sub.1-4 alkoxy, phenylC.sub.1-3 alkoxy or C.sub.1-6 alkyl group or a group --NR.sup.7 R.sup.8 or --CONR.sup.7 R.sup.8 ;R.sup.7 and R.sup.8, 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;n represents 1, 2 or 3; andA-B represents the group CH--CH.sub.2 or C.dbd.CH; and physiologically acceptable salts and solvates thereof.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：R1表示氢原子或选自C1-6烷基，C3-6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，-CO 2 R 5，-COR 5，-CONR 5 R 6或-SO 2 R 5; R 5和R 6可以相同或不同，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 不同的是氢原子或C1-6烷基; 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烷基或基团-NR 7 R 8或-CONR 7 R 8; R 7和R 8可以相同或不同，各自表示氢原子或C 1-4烷基或C 3-4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; n表示1,2或3; A-B表示基团CH-CH 2或C = CH; 及其生理上可接受的盐和溶剂合物。 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：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：US5183820A

公开(公告)日：1993-02-02

申请号：US691814

申请日：1991-04-26

申请人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Barry J. Price

发明人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Barry J. Price

IPC分类号： C07D471/04 ,  C07D487/04

CPC分类号： C07D471/04 ,  C07D487/04

摘要： The invention provides potent and selective antagonists of 5-HT at 5-HT.sub.3 receptors which are tricyclic lactams of the formula (I) ##STR1## wherein Im represents an imidazolyl group of the 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, --CO.sub.2 R.sup.5, --COR.sup.5, --CONR.sup.5 R.sup.6 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 same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group;Y represents the group CH.dbd.CH or (CH.sub.2).sub.n, wherein n represents 2 or 3;Q represents a halogen atom, or a group selected from hydroxy, C.sub.1-4 alkoxy, phenylC.sub.1-3 alkoxy, C.sub.1-6 alkyl, cyano, phenyl which may be unsubstituted or substituted by one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy groups or halogen atoms, --NR.sup.7 R.sup.8, --CONR.sup.7 R.sup.8 , --(CH.sub.2).sub.p CONR.sup.7 R.sup.8, --(CH.sub.2).sub.q NR.sup.9 R.sup.10 or --(CH.sub.2).sub.2 CO.sub.2 R.sup.11 ;Q' represents a hydrogen or a fluorine atom;and physiologically acceptable salts and solvates thereof.

摘要翻译： 本发明提供5-HT受体的有效和选择性拮抗剂，其为作为式（I）的三环内酰胺的5-HT 3受体，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，-CO 2 R 5，-COR 5，-CONR 5 R 6或-SO 2 R 5中的基团; 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 表示氢原子或C 1-6烷基; Y表示基团CH = CH或（CH 2）n，其中n表示2或3; Q表示卤原子，或选自羟基，C 1-4烷氧基，苯基C 1-3烷氧基，C 1-6烷基，氰基，可未被取代或被一个或多个C 1-4烷基，C 1-4烷氧基或羟基或卤素取代的苯基的基团 原子，-NR 7 R 8，-CONR 7 R 8， - （CH 2）p CONR 7 R 8， - （CH 2）q NR 9 R 10或 - （CH 2）2 CO 2 R 11; Q'表示氢或氟原子; 及其生理上可接受的盐和溶剂合物。