公开(公告)号：EP0126367B1

公开(公告)日：1994-10-12

申请号：EP84105158.4

申请日：1984-05-07

申请人： BEECHAM GROUP PLC

发明人： Evans, John Morris ,  Cassidy, Frederick

IPC分类号： C07D311/68 ,  A61K31/35

CPC分类号： C07D311/68

公开(公告)号：EP0274821B1

公开(公告)日：1993-03-03

申请号：EP87309235.7

申请日：1987-10-19

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Faruk, Erol Ali

IPC分类号： C07D405/04 ,  A61K31/40 ,  A61K31/445

CPC分类号： C07D405/04

公开(公告)号：EP0205292A2

公开(公告)日：1986-12-17

申请号：EP86304139.8

申请日：1986-05-30

申请人： BEECHAM GROUP PLC

发明人： Evans, John Morris ,  Stemp, Geoffrey ,  Cassidy, Frederick

IPC分类号： C07D491/04 ,  C07D491/10 ,  A61K31/435

CPC分类号： C07D491/04 ,  C07D491/10 ,  C07D491/14

摘要： A compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein:

one of R, and F 2 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R, and R 2 together are C 2 - 5 polymethylene;
either R 3 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R4 is hydrogen or R 3 and R 4 together are a bond;
R s is hydrogen; C 1-6 alkyl optionally substituted by up to three halo atoms, by hydroxy, C 1-6 alkoxy, C 1- 6 alkoxycarbonyl, carboxy, or amino optionally substituted by one or two independent C 1-6 alkyl groups or disubstituted by C 4 . 5 polymethylene; C 2 - 6 alkenyl; amino optionally substituted by a C 1-6 alkyl or C 1-6 alkenyl group or by a C 1-6 alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halogen; or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms selected from the class of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C 1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups; or (when X is 0), R s is selected from the class of carboxy, C 1- 6 alkoxycarbonyl, or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups; and
R 6 is hydrogen or C 1-6 alkyl; or
R s and R 6 together are -CH 2 -(CH 2 ) -Z-(CH2)m-wherein m and n are 0 to 2 such that m + n is 1 or 2 and Z is CH 2 , O, S or NR wherein R is hydrogen, C 1-9 alkyl, 2-7 alkanoyl, phenyl C 1-4 -alkyl, naphthylcarbonyl, phenylcarbonyl or benzyl-carbonyl optionally substituted in the phenyl or naphthyl ring by one or two of C 1-6 alkyl, C 1-6 alkoxy or halogen; or R is heteroarylcarbonyl;
or halogen, or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms X is oxygen or sulphur; or
R s , R 6 , X and N together are tetrahydroisoquinolinone or tetrahydroisoquinolin- thione optionally substituted in the phenyl ring as defined for R above;
the nitrogen-containing group in the 4-position being trans to the R 3 group when R 3 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; having pharmacological activity, including blood pressure lowering activity, a process and intermediates for their preparation and their use as pharmaceuticals.

公开(公告)号：EP0023083A1

公开(公告)日：1981-01-28

申请号：EP80302012.2

申请日：1980-06-16

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Moore, Richard William Moore

IPC分类号： C07D233/78 ,  C07D233/86 ,  C07D233/32 ,  A61K31/415

CPC分类号： C07D233/86 ,  C07D233/78

摘要： Compounds of the formula (1):
wherein:

X is O, S or H 2 ;
Y is -CH 2 -CH 2 -, -CH =CH- or -C=C-;
n is 1 to 5;
R 1 is C 1-4 alkyl;
R 2 is hydrogen or C 1-4 alkyl;
R 3 is a hydroxy or protected hydroxy;
R 4 is C 1-9 alkyl, C 3-6 cycloalkyl or C 3-8 cycloalkyl-C,- 6 alkyl; and
R 5 is hydrogen or C,- 6 alkyl; and salts thereof having useful pharmacological activity, compositions containing them and processes for their preparation.

摘要翻译： 式（I）的化合物： worin：X为O，S或H 2; Y是-CH2-CH2-，-CH = CH-或-C IDENTICAL C-; n为1至5; R 1是C 1-4烷基; R 2是氢或C 1-4烷基; R3是羟基或被保护的羟基; R 4是C 1-9烷基，C 3-8环烷基或C 3-8环烷基C 1-6烷基; 和R 5是氢或C 1-6烷基; 及其盐具有有用的药理活性，组合物包含它们和它们的制备方法。

公开(公告)号：EP0274821A1

公开(公告)日：1988-07-20

申请号：EP87309235.7

申请日：1987-10-19

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Faruk, Erol Ali

IPC分类号： C07D405/04 ,  A61K31/40 ,  A61K31/445

CPC分类号： C07D405/04

摘要： Compounds of formula (I):
wherein:

either one of R₁ and R₂ is hydrogen and the other is selected from the class of C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonyloxy, C 1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C 1-6 alkylsulphinyl, C 1-6 alkylsulphonyl, C 1-6 alkoxysulphinyl, C 1-6 alkoxysulphonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxycarbonylamino, C 1-6 alkyl-thiocarbonyl, C 1-6 alkoxy-thiocarbonyl, C 1-6 alkyl-thiocarbonyloxy, 1-mercapto C 2-7 alkyl, formyl, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C 1-6 alkyl groups, or C 1-6 alkylsulphinylamino, C 1-6 alkylsulphonylamino, C 1-6 alkoxysulphinylamino or C 1-6 alkoxysulphonylamino, or ethylenyl terminally substituted by C 1-6 alkylcarbonyl, nitro or cyano, or -C(C 1-6 alkyl)NOH or -C(C 1-6 alkyl)NNH₂, or one of R₁ and R₂ is nitro, cyano or C 1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C 1-6 alkyl or by C 2-7 alkanoyl;

one of R₃ and R₄ is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R₃ and R₄ together are C 2-5 polymethylene;

either R₅ is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R₆ is hydrogen or R₅ and R₆ together are a bond; and

n is 1 or 2;

the hydroxy group substituting the lactam group is other than at position a; and the substituted lactam group being trans to the R₅ group when R₅ is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; or a pharmaceutically acceptable salt thereof; having antihypertensive activity, a process for their preparation and their use as pharmaceuticals.

摘要翻译： 式（I）化合物： worin：或者R1和R2中的一个是氢，另一个是从类C 1-6烷基羰基的选择，C1-6烷氧羰，C 1-6烷基羰基氧基，C 1-6 alkylhydroxymethyl，硝基 基，氰基，氯，三氟甲基，C 1-6烷基亚磺酰基，C 1-6烷基磺酰基，C 1-6 alkoxysulphinyl，C1-6 alkoxysulphonyl，C 1-6烷基羰基氨基，C 1-6烷氧羰，C 1-6烷基 - 硫代羰基，C1-6烷氧基 - 硫代羰基 ，C 1-6烷基 - 硫代羰基氧基，1-巯基C 2-7烷基，甲酰基，或aminosulphinyl，氨基磺酰基或氨基羰基，氨基部分任选地被一个或两个C1-6烷基基团，或C 1-6 alkylsulphinylamino，C1-6 substituiertem 烷基磺酰，C 1-6 alkoxysulphinylamino或C 1-6 alkoxysulphonylamino，或亚乙基末端由C1-6烷基羰基，硝基或氰基，或-C（C 1-6烷基）NOH或-C（C 1-6烷基）NNH 2，或一个取代的 R 1和R 2是硝基，氰基或C 1-3烷基羰基，另一个是甲氧基或氨基，任选被一个或两个C 1-6烷基或substituiertem 由C2-7烷酰基; R3和R4中的一个是氢或C 1-4烷基且另一个是C 1-4烷基或R 3和R 4一起为C 2-5聚亚甲基; 或者R5是氢，羟基，C 1-6烷氧基或C 1-7酰氧基和R6是氢或R5和R6一起为一个键; 且n是1或2; 代内酰胺基团上的羟基比在位置的其他; 和substituiertem内酰胺基团是反式于R 5基团当R 5为羟基，C 1-6烷氧基或C 1-7酰氧基; 或其药学上可接受的盐; 有降压活性，其制备方法及其作为药物的用途。

公开(公告)号：EP0214818A3

公开(公告)日：1987-12-16

申请号：EP86306690

申请日：1986-08-29

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Stemp, Geoffrey ,  Evans, John Morris

IPC分类号： C07D311/68 ,  C07D311/70 ,  A61K31/35

CPC分类号： C07D311/70 ,  C07D311/68

摘要： Compounds of formula (I) and pharmaceutically acceptable salts thereof: R
wherein:
one of R, and R 2 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R, and R 2 together are C 2-5 -polymethylene; either R 3 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R 4 is hydrogen or R 3 and R 4 together are a bond; R 5 is hydrogen, C 1-6 alkyl optionally substituted by halogen, hydroxy, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, carboxy or amino optionally substituted by one or two independent C 1-6 alkyl groups, or C 2-6 alkenyl, amino optionally substituted by a C 1-6 alkyl or C 1-6 alkenyl group or by a C 1-6 alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halogen, or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms selected from the class of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C 1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups and R 6 is hydrogen or C 1-6 alkyl, or R 5 and R 6 together are-CH 2 -(CH 2 ) n -Z-(CH) m - wherein m and n are 0 to 2 such that m + n is 1 or 2 and Z is CH 2 , 0, S or NR wherein R is hyydrogen, C 1-9 alkyl, C 2-7 alkanoyl, phenyl C 1-4 -alkyl, naphthylcarbonyl, phenylcarbonyl or benzylcarbonyl optionally substituted in the phenyl or naphthyl ring by one or two of C 1-6 alkyl, C 1-6 alkoxy or halogen; mono- or bi-cyclic- heteroarylcarbonyl; X is oxygen or sulphur; Y and Q are electron withdrawing groups; and the nitrogen-containing group in the 4-position being trans to the R 3 group when R 3 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; having blood pressure lowering activity, a process and intermediates for their preparation and their use as pharmaceuticals.

公开(公告)号：EP0214818A2

公开(公告)日：1987-03-18

申请号：EP86306690.8

申请日：1986-08-29

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Stemp, Geoffrey ,  Evans, John Morris

IPC分类号： C07D311/68 ,  C07D311/70 ,  A61K31/35

CPC分类号： C07D311/70 ,  C07D311/68

摘要： Compounds of formula (I) and pharmaceutically acceptable salts thereof: R
wherein:

one of R, and R 2 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R, and R 2 together are C 2-5 -polymethylene; either R 3 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R 4 is hydrogen or R 3 and R 4 together are a bond; R 5 is hydrogen, C 1-6 alkyl optionally substituted by halogen, hydroxy, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, carboxy or amino optionally substituted by one or two independent C 1-6 alkyl groups, or C 2-6 alkenyl, amino optionally substituted by a C 1-6 alkyl or C 1-6 alkenyl group or by a C 1-6 alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halogen, or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms selected from the class of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C 1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups and R 6 is hydrogen or C 1-6 alkyl, or R 5 and R 6 together are-CH 2 -(CH 2 ) n -Z-(CH) m - wherein m and n are 0 to 2 such that m + n is 1 or 2 and Z is CH 2 , 0, S or NR wherein R is hyydrogen, C 1-9 alkyl, C 2-7 alkanoyl, phenyl C 1-4 -alkyl, naphthylcarbonyl, phenylcarbonyl or benzylcarbonyl optionally substituted in the phenyl or naphthyl ring by one or two of C 1-6 alkyl, C 1-6 alkoxy or halogen; mono- or bi-cyclic- heteroarylcarbonyl;
X is oxygen or sulphur;
Y and Q are electron withdrawing groups; and the nitrogen-containing group in the 4-position being trans to the R 3 group when R 3 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; having blood pressure lowering activity, a process and intermediates for their preparation and their use as pharmaceuticals.

公开(公告)号：EP0126367A1

公开(公告)日：1984-11-28

申请号：EP84105158.4

申请日：1984-05-07

申请人： BEECHAM GROUP PLC

发明人： Evans, John Morris ,  Cassidy, Frederick

IPC分类号： C07D311/68 ,  A61K31/35

CPC分类号： C07D311/68

摘要： Compounds of formula (I):
wherein:

either one of R 1 and R 2 is hydrogen and the other is selected from the class of C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonyloxy, C 1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C 1-6 alkylsulphinyl, C 1-6 alkylsulphonyl, C 1-6 alkoxysulphinyl, C 1-6 alkoxysulphonyl, C 1 - 6 alkylcarbonylamino, C 1-6 alkoxycarbonylamino, C 1-6 alkyl-thiocarbonyl, C 1-6 alkoxy-thiocarbonyl, C 1-6 alkyl-thiocarbonyloxy, C 1-6 alkyl-thiomethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C 1-6 alkyl groups, or C 1-6 alkylsulphinylamino, C 1-6 alkylsulphonylamino, C 1-6 alkoxysulphinylamino or C 1-6 alkoxysulphonylamino or ethylenyl terminally substituted by C l - 6 alkylcarbonyl, nitro or cyano, or one of R 1 and R 2 is nitro, cyano or C 1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C 1-6 alkyl groups or by C 2 - 7 alkanoyl; one of R 3 and R 4 is hydrogen or C l - 4 alkyl and the other is C l - 4 alkyl or R 3 and R 4 together are C 2 - 5 polymethylene; either R 5 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R 6 is hydrogen or R 5 and R 6 together are a bond; R 7 is selected from the class consisting of C 1 - 6 alkyl substituted by amino optionally substituted by one or two C 1-6 alkyl groups which may be the same or different; amino optionally substituted by a C 1-6 alkyl or C 1-6 alkenyl group or a C 5-8 cycloalkyl group or by a phenyl group optionally substituted by C 1-6 alkyl, C l - 6 alkoxy or halogen; or C 1-6 alkoxy, or phenoxy optionally substituted by C 1-6 alkyl, C 1-6 alkoxy or halogen; or, when X is oxygen, R 7 is selected from the class of carboxy, C 1-6 alkoxycarbonyl, or aminocarbonyl optionally substituted by one or two C 1-6 alkyl groups which may be the same or different;
R 8 is hydrogen or C 1-6 alkyl; and
X is oxygen or sulphur;
The R 8 -N-CX-R 7 group being trans to the R 5 group when R 5 and R 6 together are not a bond;

or when the compound of formula (I) contains a salifiable group, pharmaceutically acceptable salts thereof, having pharmacological activity, a process for preparing them, pharmaceutical compositions containing them, and their use in the treatment of mammals.

公开(公告)号：EP0007180A1

公开(公告)日：1980-01-23

申请号：EP79301142.0

申请日：1979-06-14

申请人： BEECHAM GROUP PLC

发明人： Cassidy, Frederick ,  Goudie, Alexander Crossan

IPC分类号： C07D249/12 ,  A61K31/41

CPC分类号： C07C255/00 ,  C07C29/147 ,  C07C45/67 ,  C07C45/673 ,  C07C45/68 ,  C07C271/16 ,  C07C309/73 ,  C07C2601/14 ,  C07D249/12 ,  Y10S514/821 ,  Y10S514/822 ,  Y10S514/927 ,  C07C49/227 ,  C07C49/24 ,  C07C49/203 ,  C07C31/20

摘要： Compounds of the formula (I):


wherein n is 3 to 5;
Y is -CH 2 -CH 2 , -CH =CH- or C≡C;
L is O or S;
R, is C 1-4 alkyl;
R : is hydrogen, C 1-4 alkyl or phenyl;
R 3 is hydroxy or protected hydroxy;
R, is hydrogen, C 1-9 alkyl, C 3-8 cycloalkyl, phenyl, naphthyl, any of which phenyl moieties or naphthyl moieties may be substituted by one or more halogen, trifluoromethyl, C 1-6 alkyl, nyd- roxy, C 1-6 alkoxy, phenyl C 1-6 alkoxy or nitro groups; or
R 2 and R 4 taken with the carbon atom to which they are joined represent a C 5 -ecycloalkyl group; and R. is C 1-6 alkyl, having similar activity to natural prostaglandins, two processes for their preparation, intermediates useful in said processes and pharmaceutical compositions containing the novel compounds of the formula (I) are disclosed.

摘要翻译： 式（I）的化合物：（I）worin n是3至5; Y为-CH 2 -CH 2，-CH = CH-或C 3BOND C-; L是O或S; R 1是C 1-4烷基; R2是氢，C1-4烷基或苯基; R 3是羟基或保护的羟基; R4是氢，C 1-9烷基，C 3-8环烷基，苯基，萘基，其中任何一个苯基部分或萘基部​​分可被一个或多个卤素，三氟甲基，C 1-6烷基，羟基，C 1-6烷氧基，苯基被substituiertem C 1-6烷氧基或硝基取代; 或R 2和R 4与所采取的碳原子它们所接合代表一个C 5-8环烷基; 且R 5是C 1-6烷基，具有相似的活性自然前列腺素，一个其制备方法，用于药物和方法中有用的中间体确实含有它们的组合物。

公开(公告)号：EP0126311B1

公开(公告)日：1989-09-13

申请号：EP84104524.8

申请日：1984-04-21

申请人： BEECHAM GROUP PLC

发明人： Evans, John Morris ,  Cassidy, Frederick

IPC分类号： C07D311/68 ,  C07D311/70 ,  C07D407/12 ,  C07D405/12 ,  A61K31/35 ,  A61K31/40 ,  A61K31/405 ,  A61K31/44

CPC分类号： C07D405/12 ,  C07D311/68 ,  C07D407/12