公开(公告)号：EP0142283B1

公开(公告)日：1991-01-30

申请号：EP84307102.8

申请日：1984-10-17

申请人： FISONS plc

发明人： Dixon, John ,  Ince, Francis ,  Tinker, Alan Charles

IPC分类号： C07C215/30 ,  C07C215/22 ,  C07C323/01 ,  C07C275/28 ,  C07C233/64 ,  C07C237/02 ,  C07C317/02 ,  C07C215/46

CPC分类号： C07D215/227 ,  C07C43/174 ,  C07C43/23 ,  C07C45/515 ,  C07C65/24 ,  C07C215/52 ,  C07C215/80 ,  C07C217/10 ,  C07C217/16 ,  C07C229/14 ,  C07C233/13 ,  C07C233/40 ,  C07C237/06 ,  C07C275/28 ,  C07C311/08 ,  C07C317/28 ,  C07C323/25 ,  C07C2601/12 ,  C07C2601/14 ,  C07C2602/08 ,  C07D215/26 ,  C07D263/14 ,  C07D319/08 ,  C07C47/575

公开(公告)号：EP0174131A3

公开(公告)日：1989-06-07

申请号：EP85305930.1

申请日：1985-08-21

申请人： FISONS plc

发明人： Baxter, Andrew John Gilby ,  Dixon, John ,  Gould, Kenneth John ,  Tinker, Alan Charles

IPC分类号： C07D211/90 ,  C07D405/12 ,  C07D409/12 ,  C07D401/12 ,  C07D401/04 ,  C07D409/14 ,  C07D417/12 ,  C07D401/06 ,  A61K31/44

CPC分类号： C07D209/48 ,  C07C45/00 ,  C07C47/55 ,  C07C47/575 ,  C07C205/44 ,  C07D231/12 ,  C07D231/20 ,  C07D233/56 ,  C07D249/08 ,  C07D305/08 ,  C07D331/04 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12

摘要： There are described compounds of formula 1,

in which R,, R 2 , R 3 , R s and R 6 are as defined in the specification and R 4 is a phenyl group carrying 3 or 4 substituents or is an unsaturated 5 membered heterocyclic group containing a single hetero-atom selected from oxygen, sulphur or nitrogen, R 4 being substituted by CF 3 , XR 22 , nitro, halogen, CN, alkyl C1 to 6, formyl dioxalanyl, -N(R 23 )COR 24 -CONR 25 R 26 , or amino which is optionally substituted by phenylsulphonyl or by trifluoroacetyl, and R 4 carries a substituent on the atom adjacent to the atom through which R 4 is connected to the remainder of the molecule,
R 22 is phenyl or alkyl C1 to 6 optionally substituted by halogen, X is 0 or S(O) n , n is 0, 1 or 2, and R 23 , R 24 , R 25 and R 26 , which may be the same or different, are each hydrogen or alkyl C1 to 6. There are also described methods for making the compounds, and their formulation and use as pharmaceuticals, eg for the treatment of cardiovascular conditions. There are further described compounds R 4 CHO which are useful in making compounds of formula I.

摘要翻译： 描述了式I，其中R 1，R 2，R 3，R 5和R 6如本说明书中所定义的式I化合物，其中R 4为含3或4个取代基的苯基，或为含有单个取代基的不饱和5元杂环基 选自氧，硫或氮的杂原子，R 4被CF 3，XR 22，硝基，卤素，CN，C 1-6烷基，二甲基丙烯酰基，-N（R 23）COR 24 -CONR 25 R 26或任选被苯基磺酰基取代的氨基取代的 或者是三氟乙酰基，R 4在与R 4连接到该分子的其余部分的原子相邻的原子上携带取代基，R22是任选被卤素取代的苯基或C 1-6烷基，X是O或S（O）n ，n为0,1或2，R 23，R 24，R 25和R 26可以相同或不同，分别为氢或C1至6的烷基。还描述了制备化合物的方法及其制备和用途 作为药物，例如用于治疗心血管疾病。 进一步描述可用于制备式I化合物的化合物R4CHO。

公开(公告)号：EP0292202A1

公开(公告)日：1988-11-23

申请号：EP88304319.2

申请日：1988-05-12

申请人： FISONS plc

发明人： Dixon, John ,  Ince, Francis ,  Springthorpe, Brian

IPC分类号： C07C215/52

CPC分类号： C07C215/54

摘要： There are described compounds of formula I,
    in which
    one of R₃₀ and R₄₀ represents a group Ra,
    and the other of R₃₀ and R₄₀ represents hydrogen or halogen,
    R₅₀ and R₆₀, which may be the same or different, each independently represent hydrogen or alkyl C 1 to C6; in addition R₆₀ may represent a group Rb,
    wherein X represents a C2 to C8 alkylene chain optionally interrupted by a double bond or by S(0) n , wherein n is 0, 1 or 2, Z represents a C 1 to C3 alkylene chain, each of X and Z being optionally substituted by OH or one or more alkyl C 1 to C6,
    R₇₀ represents hydrogen, alkyl C 1 to C6 or (CH₂) q R₁₁,
    R₁₀ and R₁₁ independently represent phenyl substituted by one or more substituents R₂₃, which may be the same or different; or R₁₀ represents a saturated carbocyclic group,
    R₁₅ represents hydrogen, alkyl C 1 to C6, or together with R₂₃ forms a (CH₂)p chain, wherein p represents 0, 1 or 2,
    R₂₀, R₂₁, R₂₂ and R₂₃ independently represent hydrogen, alkyl C 1 to C6, NHR₂₅, SH, NO₂, halogen, CF₃, SO₂R₂₆, CH₂₀H or OH, wherein R₂₅ represents hydrogen, alkyl C 1 to C6 or alkanoyl C 1 to C6 and R₂₆ represents alkyl C 1 to C6 or NH₂
    l represents 2, 3 or 4,
    q represents an integer from 1 to 6 inclusive,
    provided that when R₄₀, R₅₀ and R₇₀ each represent hydrogen and R₆₀ represents Rb,
    then Ra represents 2(3-hydroxyphenyl)ethyl, R₁₅ represents hydrogen and either

a) X represents (CH₂) p , in which p is 3, 5, 7 or 8 or
b) at least one of X and Z is substituted by either OH or one or more alkyl C 1 to C6,
    and pharmaceutically acceptable salts and solvates thereof.
There are also described processes for the preparation of the compounds of formula I and pharmaceutical compositions containing them. The compounds of the invention may be used in the treatment or prophylaxis of renal failure or cardiovascular disorders.

摘要翻译： 描述了式I的化合物，其中R30和R40中的一个代表基团Ra，，R30和R40中的另一个表示氢或卤素，R50和R60可以相同或不同， 各自独立地表示氢或C 1至C 6的烷基; 另外，R 60可以表示Rb，，其中X表示任选被双键中断的C 2〜C 8亚烷基链或S（O）n，其中n为0,1或2，Z表示C 1〜 C3亚烷基链，X和Z各自任选被OH或一个或多个C 1至C 6的烷基取代，R 70表示氢，烷基C 1至C 6或（CH 2）q R 11，R 10和R 11独立地表示被一个或多个 取代基R 23可以相同或不同; 或R 10表示饱和碳环基，R 15表示氢，C 1至C 6烷基，或与R 23一起形成（CH 2）p链，其中p表示0,1或2，R 20，R 21，R 22和R 23独立地表示氢， 烷基C 1至C 6，NHR 25，SH，NO 2，卤素，CF 3，SO 2 R 26，CH 2 OH或OH，其中R 25表示氢，C 1至C 6烷基或C 1至C 6烷酰基，R 26表示烷基C 1至C 6或NH 2 2,3或4，q表示1〜6的整数，其中R40，R50和R70各自表示氢，R60表示Rb，则Ra表示2（3-羟基苯基）乙基，R15表示氢，a） X表示（CH 2）p，其中p为3,5,7或8或b）X和Z中的至少一个被OH或一个或多个C 1 -C 6烷基取代，及其药学上可接受的盐和溶剂合物 。 还描述了制备式I化合物的方法和含有它们的药物组合物。 本发明的化合物可用于治疗或预防肾衰竭或心血管疾病。

公开(公告)号：EP0142283A3

公开(公告)日：1986-06-04

申请号：EP84307102

申请日：1984-10-17

申请人： FISONS plc

发明人： Dixon, John ,  Ince, Francis ,  Tinker, Alan Charles

IPC分类号： C07C91/30 ,  C07C91/32 ,  C07D215/22 ,  C07C149/24 ,  C07C127/19 ,  C07C103/82 ,  C07C103/50 ,  C07C103/42 ,  C07C147/02 ,  C07C143/75 ,  C07C91/44 ,  C07C43/23 ,  C07C43/174 ,  C07C121/75 ,  C07C93/14 ,  C07C149/273 ,  C07D263/14 ,  C07D317/28 ,  C07C65/03 ,  C07C149/40 ,  C07C69/157 ,  C07C69/612 ,  C07C79/36 ,  C07C47/575 ,  C07C103/76 ,  C07C103/78 ,  C07C103/737 ,  C07C103/38 ,  C07C103/60 ,  C07C103/58

CPC分类号： C07D215/227 ,  C07C43/174 ,  C07C43/23 ,  C07C45/515 ,  C07C65/24 ,  C07C215/52 ,  C07C215/80 ,  C07C217/10 ,  C07C217/16 ,  C07C229/14 ,  C07C233/13 ,  C07C233/40 ,  C07C237/06 ,  C07C275/28 ,  C07C311/08 ,  C07C317/28 ,  C07C323/25 ,  C07C2601/12 ,  C07C2601/14 ,  C07C2602/08 ,  C07D215/26 ,  C07D263/14 ,  C07D319/08 ,  C07C47/575

摘要： There are described compounds ofiformula I,
in which R, represents OH, NR 11 R 12 , CH 2 R 12 or fluorine,
R 2 , R 3 , R 11 , R 12 and R 2 , have various meanings as defined herein for example R 2 and R 3 may represent hydrogen, halogen, alkyl C1 to 6 or nitro; W represents a single bond, a disubstituted benzene or a 1,4-cyclohexanediyl group, X represents NH, 0, S, SO 2 , CO, CH 2 , CONH or-COO; Y, amongst other meanings defined herein, represents (CH 2 )q, CO, CS and SO 2 , Z represents a single bond, NR 19 , CH 2 , O, CO, S or SO 2 , in which R 10 represents hydrogen or alkyl C1 to 6, n and m each independently represent an integer from 1 to 4 inclusive, q represents an integer from 1 to 3 inclusive, p represents 0 or an integer from 1 to 3 inclusive, R 10 represents hydrogen or chlorine, R 20 , amongst other meanings defined herein may represent hydrogen, with four provises as defined herein, and pharmaceutically acceptable derivatives thereof. There are also described the use of the compounds of formula 1 as pharmaceuticals, methods for making the compounds and pharmaceutical, e.g. cardiac, compositions containing the compounds.

公开(公告)号：EP0174071A2

公开(公告)日：1986-03-12

申请号：EP85304805.6

申请日：1985-07-05

申请人： FISONS plc

发明人： Baxter, Andrew John Gilby ,  Dixon, John ,  Gould, Kenneth John ,  Fuher, John

IPC分类号： C07D211/90 ,  A61K31/44

CPC分类号： C07D211/90

摘要： There are described compounds of formula I,
in which R 2 and R 3 , which may be the same or different, each represent alkyl C1 to 6 or cycloalkyl C3 to 8,

R 7 and R 8 , which may be the same or different, each represent alkyl C1 to 6 optionally substituted by halogen, and
X, Y and Z, which may be the same or different, are each hydrogen, halogen, nitro or alkyl C1 to 6 optionally substituted by halogen, or Z is as defined above and X and Y, together with the carbon atoms to which they are attached, form a C5 to 8 carbocyclic ring, other than a benzene ring,
provided that when R 2 , R 3 , R 7 and R 8 are all methyl and X and Z are hydrogen; or when R 2 and R 3 are both ethyl, R 7 and R 8 are both methyl and X and Z are hydrogen; then Y is other I than methyl.

There are also described methods for making the compounds and their formulation and use as pharmaceuticals, e.g. for the treatment of cardiovascular conditions.

摘要翻译： 描述了式I，的化合物，其中可以相同或不同的R 2和R 3各自代表烷基C1至6或环烷基C3至8，R7和R8各自可相同或不同 表示任选被卤素取代的C 1-6的烷基，X，Y和Z可以相同或不同，各自为氢，卤素，硝基或任选被卤素取代的C 1-6的烷基，或Z如上所定义，X为 并且Y与它们所连接的碳原子一起形成除苯环之外的C5至8碳环，条件是当R 2，R 3，R 7和R 8全部为甲基且X和Z为氢时; 或当R 2和R 3均为乙基时，R 7和R 8均为乙基，X和Z为氢; 那么Y不是甲基。 还描述了制备化合物及其制剂和用作药物的方法，例如， 用于治疗心血管疾病。

公开(公告)号：EP0125803A2

公开(公告)日：1984-11-21

申请号：EP84302566.9

申请日：1984-04-16

申请人： FISONS plc

发明人： Baxter, Andrew John Gilby ,  Dixon, John ,  Gould, Kenneth John ,  McInally, Thomas ,  Tinker, Alan Charles

IPC分类号： C07D211/90 ,  C07D211/78 ,  C07D401/04 ,  C07D405/04 ,  C07D413/04 ,  C07D401/06 ,  A61K31/445

CPC分类号： C07D231/12 ,  C07C17/093 ,  C07C45/00 ,  C07C47/55 ,  C07C205/56 ,  C07D205/04 ,  C07D211/78 ,  C07D211/90 ,  C07D233/56 ,  C07D249/08 ,  C07D305/08 ,  C07D309/12 ,  C07D401/04 ,  C07D405/04 ,  C07D413/04 ,  C07C25/13

摘要： There are described compounds of formula I,

in which R 1 represents benzofurazanyl, pyridyl or phenyl, the pyridyl or phenyl being substituted,
-COOR 2 and -COOR 3 are various ester groups,
Yand Ztogetherform a bond, and additionally, when R. is an electron withdrawing group Y may be hydrogen and Z may be hydroxy,
one of R 7 and R. represents alkyl Cl to 6 and the other represents -CONR 10 R 11 ; -CSNH 2 ; -C(=NN)SR 9 ; -S(O) m R 9 ; phenyl optionally substituted by one or more of alkyl Cl to 6, halogen, alkoxy CI to 6 or nitro; alkyl Cl to 6 substituted by halogen; or furanyl,
or R 7 and R. may be the same or different and each represents phenyl optionally substituted by one or more of alkyl CI to 6, halogen, alkoxy Cl to 6 or nitro; amino; alkyl CI to 6 substituted by halogen; -CN; -CH 2 OH; -CHO or-CH(OR 9 ) 2 ,
m is 0 or 1
R 9 is alkyl CI to 6, and
R 10 and R 11 each independently represent hydrogen or alkyl Cl to 6, or together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring.
There are also described processes for making the compounds, and pharmaceutical, eg calcium antagonist, formulations containing them.

摘要翻译： 描述了式I的化合物，其中R 1表示苯并呋咱基，吡啶基或苯基，被取代的吡啶基或苯基，-COOR2和-COOR3是各种酯基，Y和Z一起形成键，此外，当 R8是吸电子基团Y可以是氢，Z可以是羟基，R 7和R 8之一表示烷基C 1-6，另一个代表-CON​​R 10 R 11; -CSNH2; -C（= NH）SR9; -S（O）MR9; 任选被一个或多个烷基C1至6，卤素，烷氧基C1至6或硝基取代的苯基; 被卤素取代的C1〜6烷基; 或呋喃基，或者R 7和R 8可以相同或不同，并且各自表示任选被一个或多个C 1-6烷基，卤素，烷氧基C 1-6或硝基取代的苯基; 氨基; 被卤素取代的C1〜6烷基; -CN; -CH2OH; -CHO或-CH（OR 9）2，m为0或1 R 9为C 1-6烷基，R 10和R 11各自独立地表示氢或烷基C 1-6，或与它们相连的氮原子一起形成5 或6元杂环。 还描述了制备化合物的方法和药物，例如钙拮抗剂，其含有它们的制剂。

公开(公告)号：EP0080220A1

公开(公告)日：1983-06-01

申请号：EP82201367.8

申请日：1982-11-01

申请人： FISONS plc

发明人： Dixon, John ,  Tinker, Alan Charles

IPC分类号： C07D413/04 ,  C07D417/04 ,  C07D491/04 ,  A61K31/445

CPC分类号： C07D413/04 ,  C07D271/12 ,  C07D417/04 ,  C07D491/04

摘要： There are described compounds of formula
in which X is oxygen or sulphur,

R 1 and R 2 , which may be the same or different, each represent alkyl C 1 to 6, -(CH 2 ) n OR 5 , or -(CH 2 ) n NR 6 R 7 , and in addition R 2 may represent hydrogen,
n is a whole number from 2 to 4 inclusive,
R 3 represents -CH 2 0H, -CN, -CH(OR 4 ) 2 , -CHO, -CH=NOH, -CF 3 , or, together with R 2 forms a chain -CHOH-,
R 4 represents alkyl C 1 to 6,
R s represents alkyl C 1 to 6 or phenyl,
R 6 and R 7 , which may be the same or different, each represent alkyl C 1 to 6 optionally substituted by phenyl, and
R 8 is alkyl C 1 to 6,
and pharmaceutically acceptable acid addition salts of those compounds containing a basic nitrogen atom.

There are also described methods for making the compounds and pharmaceutical, e.g. cardiac, compositions containing them.

摘要翻译： 中描述了式I的化合物，其中X是氧或硫，R 1和R 2，它们可以是相同的或不同的，各自代表烷基的C 1〜6， - （CH 2）n或5，或 - （CH2 ）N NR6R7，和（除R2可以代表氢，n是整数2至4包容，R 3 darstellt -CH 2 OH，-CN，-CH OR4）2，-CHO，-CH = NOH，-CF 3，或 ，其中R 2点形成一个链-CHOH-，R 4 darstellt烷基的C 1〜6，R 5 darstellt烷基的C 1〜6或苯基，R6和R7，其可以是相同或不同在一起，各自代表烷基的C 1〜6 OPTIONALLY substituiertem 由苯基，并且R8是烷基的C 1〜6的化合物，以及那些含有一个碱性氮原子的药学上可接受的酸加成盐。 所以有描述的方法制备的化合物和药物，E.G. 心脏，组成包含它们。

公开(公告)号：EP0248523B1

公开(公告)日：1991-10-16

申请号：EP87303666.9

申请日：1987-04-27

申请人： FISONS plc

发明人： Appleton, Richard Anthony ,  Burford, Sidney Clifford ,  Dixon, John

IPC分类号： C07D231/38 ,  A61K31/415

CPC分类号： C07D231/38

公开(公告)号：EP0174071A3

公开(公告)日：1988-08-31

申请号：EP85304805

申请日：1985-07-05

申请人： FISONS plc

发明人： Baxter, Andrew John Gilby ,  Dixon, John ,  Gould, Kenneth John ,  Fuher, John

IPC分类号： C07D211/90 ,  A61K31/44

CPC分类号： C07D211/90

摘要： There are described compounds of formula I,
in which R 2 and R 3 , which may be the same or different, each represent alkyl C1 to 6 or cycloalkyl C3 to 8,
R 7 and R 8 , which may be the same or different, each represent alkyl C1 to 6 optionally substituted by halogen, and X, Y and Z, which may be the same or different, are each hydrogen, halogen, nitro or alkyl C1 to 6 optionally substituted by halogen, or Z is as defined above and X and Y, together with the carbon atoms to which they are attached, form a C5 to 8 carbocyclic ring, other than a benzene ring, provided that when R 2 , R 3 , R 7 and R 8 are all methyl and X and Z are hydrogen; or when R 2 and R 3 are both ethyl, R 7 and R 8 are both methyl and X and Z are hydrogen; then Y is other I than methyl. There are also described methods for making the compounds and their formulation and use as pharmaceuticals, e.g. for the treatment of cardiovascular conditions.

摘要翻译： 描述了式I，的化合物，其中可以相同或不同的R 2和R 3各自表示烷基C1至6或环烷基C3至8，R7和R8各自可相同或不同 表示任选被卤素取代的C 1-6的烷基，X，Y和Z可以相同或不同，各自为氢，卤素，硝基或任选被卤素取代的C 1-6的烷基，或Z如上所定义，X为 并且Y与它们所连接的碳原子一起形成除苯环之外的C5至8碳环，条件是当R 2，R 3，R 7和R 8全部为甲基且X和Z为氢时; 或当R 2和R 3均为乙基时，R 7和R 8均为乙基，X和Z为氢; 那么Y不是甲基。 还描述了制备化合物及其制剂和用作药物的方法，例如， 用于治疗心血管疾病。

公开(公告)号：EP0248523A1

公开(公告)日：1987-12-09

申请号：EP87303666.9

申请日：1987-04-27

申请人： FISONS plc

发明人： Appleton, Richard Anthony ,  Burford, Sidney Clifford ,  Dixon, John

IPC分类号： C07D231/38 ,  A61K31/415

CPC分类号： C07D231/38

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

R 1 represents hydrogen, alkyl, alkanoyl or alkyl substituted by Ar 1 ,
R 3 , R 4 and R 5 , which may be the same or different, each independently represent hydrogen, alkyl or Ar 3 ,
Ar,, Ar 2 and Ar 3 , which may be the same or different, independently represent phenyl or phenyl substituted by one or more of alkyl, hydroxy, alkoxy, NR 6 R 7 or halogen,
R 6 and R 7 , which may be the same or different, independently represent hydrogen or alkyl,
and pharmaceutically acceptable acid addition salts thereof.

Compositions containing the compounds and methods for their preparation are also described.
The compounds are indicated for use as pharmaceutical, eg anti-inflammatory agents.

摘要翻译： 描述了式I的化合物，其中R 1表示氢，烷基，烷酰基或被Ar 1，R 3，R 4和R 5取代的烷基，其可以相同或不同，各自独立地表示氢，烷基或Ar 3，Ar 1 可以相同或不同的Ar2和Ar3独立地表示苯基或被一个或多个烷基，羟基，烷氧基，NR6R7或卤素取代的苯基，R6和R7可以相同或不同，独立地表示氢或 烷基和其药学上可接受的酸加成盐。 还描述了含有化合物的组合物及其制备方法。 化合物指示用作药物，例如抗炎剂。