公开(公告)号：US5196534A

公开(公告)日：1993-03-23

申请号：US704099

申请日：1991-05-22

申请人： John W. F. Whitehead ,  Keith Mills ,  Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North

发明人： John W. F. Whitehead ,  Keith Mills ,  Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North

IPC分类号： C07B61/00 ,  C07D211/86 ,  C07D471/04

CPC分类号： C07D471/04 ,  C07D211/86

摘要： The invention relates to a process for the preparation of a compound of formula (I) ##STR1## wherein R represent a hydrogen atom or a methyl or ethyl group, which comprises cyclising a compound of formul (IV) ##STR2## Where R represents a hydrogen atom, the compound of formula (IV) may optionally be alkylated to produce a compound in whcich R is methyl or ethyl.The compound of formula (I) is useful as an intermediate in the preparation of 2,3,4,5-tetrahydro-2-[(imidazol-4(or 5)-yl)methyl]-1H-pyrido[4,3-b]indol-1-ones having 5-HT.sub.3 antagonist activity.

公开(公告)号：US5116984A

公开(公告)日：1992-05-26

申请号：US333967

申请日：1989-04-06

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

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

IPC分类号： A61K31/415 ,  A61P25/00 ,  C07D233/54 ,  C07D233/64 ,  C07D401/06 ,  C07D403/06

CPC分类号： C07D233/64 ,  C07D401/06 ,  C07D403/06

摘要： The invention relates to imidazole derivatives of the general formula (I) ##STR1## wherein Im represents an imidazolyl group of formula: ##STR2## A represents the group CH or a nitrogen atom; R.sup.1 and R.sup.2, which may be the same or different, and may be attached to either the same or different fused rings of the naphthalene moiety, each represents a hydrogen atom, a halogen atom, or a hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 alkyl or C.sub.1-4 alkylthio group, and one of R.sup.1 and R.sup.2 may also represent a group --NR.sup.3 R.sup.4 (wherein R.sup.3 and R.sup.4, which may be the same or different, each represents a hydrogen atom or a C.sub.1-4 alkyl 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;R.sup.5, R.sup.6, R.sup.7, are as defined in the specification; and physiologically acceptable salts and solvates thereof.

公开(公告)号：US5013733A

公开(公告)日：1991-05-07

申请号：US485532

申请日：1990-02-27

申请人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Thomas Miller ,  Anthony D. Baxter ,  Kevin I. Hammond

发明人： Ian H. Coates ,  Alexander W. Oxford ,  Peter C. North ,  Thomas Miller ,  Anthony D. Baxter ,  Kevin I. Hammond

IPC分类号： C07D453/02 ,  A61K31/435 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P25/00 ,  A61P25/04 ,  A61P25/18 ,  A61P25/20 ,  A61P25/28 ,  A61P43/00 ,  C07D519/00

CPC分类号： C07D519/00

摘要： The invention provides lactam derivatives of the general formula (I) ##STR1## wherein 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.3, --COR.sup.3, --CONR.sup.3 R.sup.4 or --SO.sub.2 R.sup.3 (wherein R.sup.3 and R.sup.4, 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.3 does not represent a hydrogen atom when R.sup.1 represents a group --CO.sub.2 R.sup.3 or --SO.sub.2 R.sup.3);and R.sup.2 represents a group of formula (a), (b) or (c): ##STR2## wherein R.sup.5 represents a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl or phenylC.sub.1-3 alkyl group;n represents 2, 3 or 4;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 --NH.sup.6 R.sup.7 or --CONR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7, 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 of formula (I) are potent and selective antagonists of 5-hydroxytryptamine at 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：US4985422A

公开(公告)日：1991-01-15

申请号：US343359

申请日：1989-04-26

申请人： Peter C. North ,  Alexander W. Oxford ,  Ian H. Coates ,  Paul J. Beswick

发明人： Peter C. North ,  Alexander W. Oxford ,  Ian H. Coates ,  Paul J. Beswick

IPC分类号： A61K31/435 ,  A61K31/55 ,  A61P43/00 ,  C07D491/04 ,  C07D491/048 ,  C07D495/04

CPC分类号： C07D491/04 ,  C07D495/04

摘要： Compounds which are potent and selective antagonists of the effect of 5-HT.sub.3 receptors and are useful in the treatment of psychotic disorders, anxiety, and nausea and vomiting, of the general formula (I) ##STR1## wherein Im represents an imidazolyl group of the formula (a), (b) or (c): ##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 or 2;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 ; andX represents an oxygen or a sulphur atom, and, when Im represents an imidazolyl group of formula (c), X may also represent the group NR.sup.6, where R.sup.6 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 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 ; and physiologically acceptable salts or solvates thereof.

公开(公告)号：US4672067A

公开(公告)日：1987-06-09

申请号：US625648

申请日：1984-06-28

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

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

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16 ,  C07D209/48 ,  C07D471/04

CPC分类号： C07D209/16

摘要： Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents CHO, COR.sub.8, CO.sub.2 R.sub.8, CONR.sub.9 R.sub.10, CSNR.sub.9 R.sub.10 or SO.sub.2 NR.sub.9 R.sub.10, whereR.sub.8 represents alkyl, cycloalkyl, aryl or aralkyl,R.sub.9 represents hydrogen or alkyl, andR.sub.10 represents hydrogen or alkyl, cycloalkyl, aryl or aralkyl;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7 each independently represents hydrogen or C.sub.1-3 alkyl;R.sub.5 represents hydrogen, or alkyl, cycloalkyl, alkenyl or aralkyl, orR.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the attached nitrogen atom form a saturated monocyclic 5- to 7-membered ring; andAlk represents C.sub.2-3 alkylene chain optionally substituted by not more than two C.sub.1-3 alkyl groups;and physiologically acceptable salts and solvates thereof. The compounds are potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using pharmaceutically acceptable carriers or excipients. The compounds may be prepared by, for example, reaction of an aminoalkyl indole with an acid of formula R.sub.1 OH or an acylating agent corresponding thereto or with an inorganic cyanate or an organic isocyanate or isothiocyanate in order to introduce the desired R.sub.1 group at the 5-position on the indole nucleus.

摘要翻译： 公开了式（I）的化合物其中R 1表示CHO，COR8，CO 2 R 8，CONR 9 R 10，CSNR 9 R 10或SO 2 NR 9 R 10，其中R 8表示烷基，环烷基，芳基或芳烷基，R 9表示氢或烷基，R 10表示氢 或烷基，环烷基，芳基或芳烷基; R2，R3，R4，R6和R7各自独立地表示氢或C1-3烷基; R5表示氢或烷基，环烷基，烯基或芳烷基，或R4和R5一起形成芳烷叉基或R4和R5与连接的氮原子一起形成饱和的单环5-至7-元环; 并且Alk表示任选被不多于两个C 1-3烷基取代的C 2-3亚烷基链; 及其生理上可接受的盐和溶剂合物。 这些化合物潜在地可用于治疗偏头痛，并且可以使用药学上可接受的载体或赋形剂以常规方式配制成药物组合物。 化合物可以通过例如氨基烷基吲哚与式R1OH的酸或对应于其的酰化剂或与无机氰酸酯或有机异氰酸酯或异硫氰酸酯反应制备，以便在5- 在吲哚核上的位置。

公开(公告)号：US4636521A

公开(公告)日：1987-01-13

申请号：US626383

申请日：1984-06-29

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

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

IPC分类号： C07D209/14 ,  A61K31/40 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/404 ,  A61P9/00 ,  A61P25/04 ,  C07D209/16 ,  C07D209/48 ,  C07D471/04

CPC分类号： C07D209/16

摘要： Compounds are disclosed of general formula (I) ##STR1## wherein R.sub.1 represents an alkyl, cycloalkyl, aryl or aralkyl group;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or a C.sub.1-3 alkyl group;R.sub.5 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl or an aralkyl group; or R.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a saturated monocyclic 5- to 7-membered ring; Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups; and physiologically acceptable salts, solvates and bioprecursors thereof. The compounds are described as potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using one or more pharmaceutically acceptable carriers or excipients. Various processes for the preparation of the compounds are disclosed including, for example, a process involving reaction of an aminoalkyl indole with a sulphonylating agent in order to introduce the --SO.sub.2 -- group at the 5-position on the indole nucleus.

摘要翻译： 公开了通式（I）的化合物其中R 1表示烷基，环烷基，芳基或芳烷基; R 2，R 3，R 4，R 6和R 7可以相同或不同，各自表示氢原子或C 1-3烷基; R5表示氢原子或烷基，环烷基，烯基或芳烷基; 或R 4和R 5一起形成亚烷基或R 4和R 5与它们所连接的氮原子一起形成饱和的单环5-至7-元环; Alk表示含有两个或三个碳原子的亚烷基链，其可以是未取代的或被不多于两个C 1-3烷基取代; 和其生理上可接受的盐，溶剂化物和生物前体。 这些化合物被描述为潜在地可用于治疗偏头痛，并且可以使用一种或多种药学上可接受的载体或赋形剂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，包括例如涉及氨基烷基吲哚与磺酰化剂反应的方法，以便在吲哚核上的5-位引入-SO 2 - 基团。

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.

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：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：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.