公开(公告)号：EP0164204A1

公开(公告)日：1985-12-11

申请号：EP85302902.3

申请日：1985-04-25

申请人： FISONS plc

发明人： Hashimoto, Masashi ,  Robinson, David Hulme

IPC分类号： A61K31/505 ,  C07D401/12 ,  C07D403/12 ,  C07D417/12 ,  C07D239/42 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04

CPC分类号： C07D239/42 ,  C07D239/47 ,  C07D239/52 ,  C07D401/04 ,  C07D403/04 ,  C07D417/12

摘要： There are described compounds of formula I,
in which one of the groups R and R 3 has no significance and the other is hydrogen, phenyl or alkyl Cl to 6 optionally substituted by phenyl, and when R 3 has no significance R can additionally represent alkanoyl Cl to 6,
one of the bonds --- is a double bond and the other is a single bond,
Ri, and at least one of R 2 , R 4 and R 5 , may be the same or different and are selected from a pyridinyl, pyridimidinyl, thiazolyl, pyrazinyl, pyridazinyl, imidazolyl and phenyl ring, which rings may optionally be substituted by one or more of the groups halogen, -COOR 5 , -COR 5 , -CN, -CONH 2 , -S0 2 NR 5 R 6 , -NR 5 R 6 , -OR 5 or alkyl Cl to 6 which latter is optionally substituted by fluorine,
R 5 and R 6 , which may be the same or different, each represent hydrogen or alkyl Cl to 6 optionally substituted by mono- or di-alkyl (Cl to 6) amino,
and the remainder of R 2 , R 4 and R 5 are selected from hydrogen, hydroxy, alkyl Cl to 6 and alkoxy Cl to 6 in addition to the significances given above,
or R 1 , and one of R 4 and R 5 have the significances given above and anadjacent pair of R 2 , R 4 and R 5 together form a -CH =CH-CH =CH- chain, or a pharmaceutically acceptable acid addition salt thereof.
Also described are processes for making certain of the compounds of formula I, formulations containing the compounds of formula I and their use as pharmaceuticals.

摘要翻译： 描述了式I的化合物，其中R和R3之一没有意义，另一个是氢，苯基或任选被苯基取代的C 1-6的烷基，当R 3没有意义时，R可以另外表示 烷酰基C1至6，一个键---是双键，另一个是单键，R 1，且R 2，R 4和R 5中的至少一个可以相同或不同，并且选自吡啶基， 吡啶基，哒嗪基，咪唑基和苯环，该环可任选被一个或多个卤素，-COOR 5，-COR 5，-CN，-CONH 2，-SO 2 NR 5 R 6，-NR 5 R 6，-OR 5或烷基 后者任选被氟取代的C 1-6，各自可以相同或不同，表示氢或任选被一或二 - 烷基（C 1-6）氨基取代的C 1-6烷基，其余 的R 2，R 4和R 5除了符号之外还选自氢，羟基，烷基C1至6和烷氧基C1至6 上述给出的化合物，或R1，R4和R5之一具有上述含义，R2，R4和R5的相邻对一起形成-CH = CH-CH = CH-链或其药学上可接受的酸加成盐。 还描述了制备某些式I化合物的方法，其含有式I化合物的制剂及其作为药物的用途。

公开(公告)号：EP0183398B1

公开(公告)日：1989-04-12

申请号：EP85307931.7

申请日：1985-11-01

申请人： FISONS plc

发明人： Bennion, Colin ,  Marriott, David Peter ,  Cook, Anthony Ronald ,  Robinson, David Hulme

IPC分类号： C07C109/12 ,  C07C143/78 ,  C07C149/20 ,  C07C153/07 ,  C07D213/53 ,  C07D333/22 ,  C07D209/40 ,  C07D277/28 ,  C07D285/36 ,  C07K5/06 ,  A61K31/00

CPC分类号： C07D213/53 ,  A61K38/00 ,  C07C243/34 ,  C07D209/40 ,  C07D277/28 ,  C07D285/36 ,  C07D333/22 ,  C07K5/022

公开(公告)号：EP0217519B1

公开(公告)日：1992-02-05

申请号：EP86306325.1

申请日：1986-08-15

申请人： FISONS plc

发明人： Brown, Roger Charles ,  Robinson, David Hulme ,  Dixon, John

IPC分类号： C07D285/12 ,  C07D417/04 ,  A61K31/41

CPC分类号： C07D253/06 ,  A61K38/00 ,  C07D271/10 ,  C07D285/12 ,  C07D285/135 ,  C07D285/16 ,  C07D417/04 ,  C07K5/0222 ,  C07K5/06086

公开(公告)号：EP0137746A3

公开(公告)日：1986-01-08

申请号：EP84306256

申请日：1984-09-13

申请人： FISONS plc

发明人： Robinson, David Hulme

IPC分类号： C07C109/02 ,  C07C109/04 ,  C07C149/23 ,  C07C149/273 ,  C07C153/07 ,  C07D295/22 ,  C07K05/06 ,  A61K31/195 ,  A61K31/265 ,  A61K31/395 ,  A61K37/02

CPC分类号： C07C243/00 ,  A61K38/00 ,  C07K5/022

摘要： There are described compounds of formula I,
in which
Z is R 2 CH (COOH) NH- or R 1 SCH 2 -, R 1 is hydrogen or R 8 CO-, R 8 is alkyl C1 to 10 or phenyl, R is hydrogen, alkyl C1 to 6, or alkyl C1 to 6 substituted by phenyl, -NH 2 , -COOH or by alkyl C1 to 6 thio, R 2 is hydrogen, alkyl C1 to 10, cycloalkyl C3 to 10, phenyl, phenylalkyl C7 to 12, alkoxy C1 to 6 - alkyl C1 to 6, alkyl C1 to 6 - thioalkyl C1 to 6, phenyloxyalkyl C7 to 12 or phenylthioalkyl C7 to 12, R. and R 5 , which may be the same or different, are each hydrogen, alkyl C1 to 10, cycloalkyl C3 to 10, phenylalkyl C7 to 12, or phenyl; the phenyl and phenylalkyl each optionally being substituted by one or more alkyl C1 to 6, alkoxy C1 to 6 or halogen groups, or R. and R 5 together form a - (CH 2 ),,- or - (CW 2 ) 5 - chain, and R 6 is hydrogen, alkyl C1 to 6 or phenylalkyl C7 to 12, and pharmaceutically acceptable salts and esters thereof. There are also described processes for making the compounds and their formulation and use as pharmaceuticals, eg. angiotensin converting enzyme inhibitors.

摘要翻译： 描述了式I的化合物，ZCHRCON（R4NH5）CHR6COOHI，其中Z是R2CH（COOH）NH-或R1SCH2-，R1是氢或R8CO-，R6是烷基C1至10或苯基，R是氢，烷基C1 至6，或由苯基，-NH 2，-COOH或C 1-6烷基取代的C 1-6烷基，R 2为氢，C 1-10烷基，C 3-10环烷基，苯基，苯基烷基C7至12，烷氧基C1至6 - 烷基C1至6，烷基C1至6-硫代烷基C1至6，苯氧基烷基C7至12或苯硫基烷基C7至12，R4和R5可相同或不同，分别为氢，烷基C1至10，环烷基C3至 10，苯基烷基C7至12，或苯基; 各自任选被一个或多个C 1-6烷基，烷氧基C1至6或卤素基团取代的苯基和苯基烷基，或者R4和R5一起形成 - （CH 2）4 - 或 - （CH 2）5 - 链，并且R 6是 氢，烷基C1至6或苯基烷基C7至12，及其药学上可接受的盐和酯。 还描述了制备化合物及其制剂和用作药物的方法，例如。 血管紧张素转换酶抑制剂。

公开(公告)号：EP0137746A2

公开(公告)日：1985-04-17

申请号：EP84306256.3

申请日：1984-09-13

申请人： FISONS plc

发明人： Robinson, David Hulme

IPC分类号： C07C109/02 ,  C07C109/04 ,  C07C149/23 ,  C07C149/273 ,  C07C153/07 ,  C07D295/22 ,  C07K5/06 ,  A61K31/195 ,  A61K31/265 ,  A61K31/395 ,  A61K37/02

CPC分类号： C07C243/00 ,  A61K38/00 ,  C07K5/022

摘要： There are described compounds of formula I,
in which

Z is R 2 CH (COOH) NH- or R 1 SCH 2 -,
R 1 is hydrogen or R 8 CO-,
R 8 is alkyl C1 to 10 or phenyl,
R is hydrogen, alkyl C1 to 6, or alkyl C1 to 6 substituted by phenyl, -NH 2 , -COOH or by alkyl C1 to 6 thio,
R 2 is hydrogen, alkyl C1 to 10, cycloalkyl C3 to 10, phenyl, phenylalkyl C7 to 12, alkoxy C1 to 6 - alkyl C1 to 6, alkyl C1 to 6 - thioalkyl C1 to 6, phenyloxyalkyl C7 to 12 or phenylthioalkyl C7 to 12,
R. and R 5 , which may be the same or different, are each hydrogen, alkyl C1 to 10, cycloalkyl C3 to 10, phenylalkyl C7 to 12, or phenyl; the phenyl and phenylalkyl each optionally being substituted by one or more alkyl C1 to 6, alkoxy C1 to 6 or halogen groups, or
R. and R 5 together form a - (CH 2 ),,- or - (CW 2 ) 5 - chain, and
R 6 is hydrogen, alkyl C1 to 6 or phenylalkyl C7 to 12, and pharmaceutically acceptable salts and esters thereof.

There are also described processes for making the compounds and their formulation and use as pharmaceuticals, eg. angiotensin converting enzyme inhibitors.

摘要翻译： 描述了式I的化合物，ZCHRCON（R4NH5）CHR6COOHI，其中Z是R2CH（COOH）NH-或R1SCH2-，R1是氢或R8CO-，R6是烷基C1至10或苯基，R是氢，烷基C1 至6，或由苯基，-NH 2，-COOH或C 1-6烷基取代的C 1-6烷基，R 2为氢，C 1-10烷基，C 3-10环烷基，苯基，苯基烷基C7至12，烷氧基C1至6 - 烷基C1至6，烷基C1至6-硫代烷基C1至6，苯氧基烷基C7至12或苯硫基烷基C7至12，R4和R5可相同或不同，分别为氢，烷基C1至10，环烷基C3至 10，苯基烷基C7至12，或苯基; 各自任选被一个或多个C 1-6烷基，烷氧基C1至6或卤素基团取代的苯基和苯基烷基，或者R4和R5一起形成 - （CH 2）4 - 或 - （CH 2）5 - 链，并且R 6是 氢，烷基C1至6或苯基烷基C7至12，及其药学上可接受的盐和酯。 还描述了制备化合物及其制剂和用作药物的方法，例如。 血管紧张素转换酶抑制剂。

公开(公告)号：EP0384636A1

公开(公告)日：1990-08-29

申请号：EP90301579.0

申请日：1990-02-14

申请人： FISONS plc

发明人： Baxter, Andrew John Gilby ,  Robinson, David Hulme ,  Brown, Roger Charles

IPC分类号： C07C327/04 ,  A61K31/265 ,  C07C323/60 ,  A61K31/095 ,  C07D207/09 ,  C07D277/04 ,  C07F9/09

CPC分类号： C07F9/5721 ,  C07C323/60 ,  C07C327/32 ,  C07C2601/08 ,  C07D207/10 ,  C07D207/12 ,  C07D277/06 ,  C07F9/3808

摘要： There are described compounds of formula I, processes for their preparation and pharmaceutical formulations containing them,
ZCHR₁COR₂      I
in which R₂ is a group of formula II,
-NR x CHR y COOH      II
in which R x and R y are each alkyl optionally substituted by phenyl; phenylalkyl C7 to 12, phenyl, phenyloxyalkyl, N-alkyl, O-alkyl, or together R x and R y may form a heterocyclic group optionally substituted by alkyl, phenyl; phenylalkyl C7 to 12, phenyl, phenyloxyalkyl, N-alkyl, O-alkyl, or one of R x and R y may be hydrogen,
provided that one of R x and R y , the heterocyclic group formed by R x and R y or the optional substituents is substituted by one or two groups -COOR₉
R₉ is phenyl, -(CH₂) x CONR₁₄R₁₅, -(CH₂) y COOR₁₆ or alkyl optionally substituted by phenyl;
R₁₄, R₁₅, R₁₆, x and y, are as described in the specification,
and pharmaceutically acceptable salts thereof.

摘要翻译： 描述了式I的化合物，其制备方法和含有它们的药物制剂，其中R 2是式II基团的ZCHR1COR2I，其中Rx和Ry各自为烷基任选被苯基取代的-NR x CHR y COOH II; 苯基烷基C7至12，苯基，苯氧基烷基，N-烷基，O-烷基或一起Rx和Ry可以形成任选被烷基，苯基取代的杂环基; 苯基烷基C7至12，苯基，苯氧基烷基，N-烷基，O-烷基或Rx和Ry中的一个可以是氢，条件是Rx和Ry中的一个，由Rx和Ry形成的杂环基或任选的取代基被 一个或两个基团-COOR 9 R 9是苯基， - （CH 2）x CONR 14 R 15， - （CH 2）y COOR 16或任选被苯基取代的烷基; R14，R15，R16，x和y如说明书中所述及其药学上可接受的盐。

公开(公告)号：EP0217519A1

公开(公告)日：1987-04-08

申请号：EP86306325.1

申请日：1986-08-15

申请人： FISONS plc

发明人： Brown, Roger Charles ,  Robinson, David Hulme ,  Dixon, John

IPC分类号： C07D285/12 ,  C07D417/04 ,  A61K31/41

CPC分类号： C07D253/06 ,  A61K38/00 ,  C07D271/10 ,  C07D285/12 ,  C07D285/135 ,  C07D285/16 ,  C07D417/04 ,  C07K5/0222 ,  C07K5/06086

摘要： There are described compounds of formula I,
in which Y is S, 0 or NR 9 ,

n is 0 or 1,
R 9 is hydrogen or alkyl C 1 to 10,
R 3 is hydrogen, alkyl C 1 to 10, cycloalkyl C3 to 10, CF 3 , SR 10 , a 5 or 6 membered heterocyclic group containing one or more S, O or N atoms, NR 4 R 5 , phenyl or phenylalkyl C7 to 12, the phenyl, phenylalkyl and heterocyclic groups optionally being fused to a further phenyl group, the heterocyclic group and any phenyl group optionally being substituted by alkyl C 1 to 6, halogen, alkoxy C 1 to 6, nitro, nitrile, CF 3 , SR 6 , NR 7 R 11 or hydroxy,
R 6 , R 7 and R,,, which may be the same or different, are each hydrogen or alkyl C 1 to 10,
R, and R s , which may be the same or different, are each hydrogen, alkyl C 1 to 10 or phenyl,
R, 10 is alkyl C 1 to 10,
X, is S or 0, and
D is a chain comprising from 2 -16 atoms, which chain carries an O or S containing substituent at a position 2 -6 atoms away from the group C=X,,
and pharmaceutically acceptable salts, esters and amides thereof,
there are also described methods for making the compounds and pharmaceutical formulations, eg for the treatment of hypertension, containing them.

公开(公告)号：EP0183398A1

公开(公告)日：1986-06-04

申请号：EP85307931.7

申请日：1985-11-01

申请人： FISONS plc

发明人： Bennion, Colin ,  Marriott, David Peter ,  Cook, Anthony Ronald ,  Robinson, David Hulme

IPC分类号： C07C109/12 ,  C07C143/78 ,  C07C149/20 ,  C07C153/07 ,  C07D213/53 ,  C07D333/22 ,  C07D209/40 ,  C07D277/28 ,  C07D285/36 ,  C07K5/06 ,  A61K31/00

CPC分类号： C07D213/53 ,  A61K38/00 ,  C07C243/34 ,  C07D209/40 ,  C07D277/28 ,  C07D285/36 ,  C07D333/22 ,  C07K5/022

摘要： There are described compounds of formula I,

in which Z is R 2 CH(COOH)NH-, R 1 SCH 2 - or Ph(CH 2 ) P PO(OH)-,

Ph is phenyl,
p is an integer from 1 to 6,
R, is hydrogen or R B CO-,
R 8 is alkyl C1 to 10 or phenyl,
R is hydrogen or alkyl C1 to 10,
R2 is alkyl C1 to 10 or phenylalkyl C7 to 12,
R 4 andR 5 , which may be the same or different, are each hydrogen, phenyl, naphthyl; a 5 or 6 membered alicyclic or heterocyclic ring each of which is optionally fused to a benzene ring; cycloalkyl containing 3 to 7 carbon atoms; or alkyl C1 to 10 optionally substituted by phenyl, napthyl or a 5 or 6 membered heterocyclic ring which latter is optionally fused to a benzene ring,

the phenyl, naphthyl or 5 or 6 membered alicyclic or heterocyclic ring (which latter two are optionally fused to a benzene ring (are all optionally substituted by one or more alkyl C1 to 10, alkoxy C1 to 10, halogen, phenylalkyl C7 to 12, phenylalkoxy C7 to 12, phenyl, hydroxy, =0, fluoroalkyl C1 to 10, cyano, nitro, phenylsulphonamido, dialkyl (C1 to 10) -amino-alkoxy (C1 to 10), alkylthio C1 to 10, or dialkyl (C1 to 10)-amino,
or R 4 and R 5 together form a - (CH 2 ) 4 -, -(CH 2 ) 5 -,
chain

R 6 is hydrogen or alkyl C1 to 10,
q is 2 or 3,
n is 0 or 1,
Y is hydroxy or -NHS0 2 R 9 , and
R 9 is alkyl C1 to 10,

and pharmaceutically acceptable salts, esters and amides thereof.
There are also described methods for making the compounds, formulations containing them and their use, eg as antihypertensives.