公开(公告)号：US4937243A

公开(公告)日：1990-06-26

申请号：US136913

申请日：1987-12-22

申请人： Roger E. Markwell ,  Stephen A. Smith ,  Ian Hughes

发明人： Roger E. Markwell ,  Stephen A. Smith ,  Ian Hughes

IPC分类号： C07D209/20 ,  C07D295/185 ,  C07K5/06

CPC分类号： C07D295/185 ,  C07D209/20 ,  C07K5/06043

摘要： Novel compounds of the formula (I), processes for their preparation and their use as collagenase inhibitors are described: ##STR1## in which R.sub.1 is hydroxy; alkoxy; aryloxy; aralkyloxy; --NR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are hydrogen or alkyl, or R.sub.6 and R.sub.7 together with the N-atom to which they are bonded form a 5- to 7-membered ring with an optional heteroatom; --NHCH(R.sub.8)COR.sub.9 where R.sub.8 is hydrogen; alkyl optionally substituted by hydroxy, alkoxy, --NR.sub.6 R.sub.7, quanidine, CO.sub.2 H, CONH.sub.2, SH, or S-alkyl; or CH.sub.2 -AR where Ar is optionally substituted aryl; and R.sub.9 is hydroxy, alkoxy or --NR.sub.6 R.sub.7.R.sub.2 is hydrogen or acyl.R.sub.3 is C.sub.3-6 alkyl.R.sub.4 is hydrogen; alkyl; --CH.sub.2 R.sub.10 where R.sub.10 is optionally substituted phenyl or heteroaryl; or --CH(R.sub.12)O--R.sub.11 where R.sub.11 is hydrogen; alkyl; or --CH.sub.2 Ph where Ph is optionally substituted phenyl; and R.sub.12 is hydrogen or alkyl.R.sub.5 is hydrogen; alkyl; or --CH(R.sub.13)COR.sub.14 where R.sub.13 is hydrogen or alkyl; and R.sub.14 is hydroxy, alkoxy or --NR.sub.6 R.sub.7.

公开(公告)号：US5109000A

公开(公告)日：1992-04-28

申请号：US517391

申请日：1990-04-30

申请人： Roger E. Markwell ,  Stephen A. Smith ,  Ian Hughes

发明人： Roger E. Markwell ,  Stephen A. Smith ,  Ian Hughes

IPC分类号： C07D209/20 ,  C07D295/185 ,  C07K5/06

CPC分类号： C07D295/185 ,  C07D209/20 ,  C07K5/06043

摘要： Novel compounds of the formula (I), processes for their preparation and their use as collagenase inhibitors are described: ##STR1## in which R.sub.1 is hydroxy; alkoxy; aryloxy; aralkyloxy; --NR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are hydrogen or alkyl, or R.sub.6 and R.sub.7 together with the N-atom to which they are bonded form a 5- to 7-membered ring with an optional heteroatom; --NHCH(R.sub.8)COR.sub.9 is hydrogen; alkyl optionally substituted by hydroxy, alkoxy, --NR.sub.6 R.sub.7, quanidine; CO.sub.2 H, CONH.sub.2, SH, or S-alkyl; or CH.sub.2 --AR where Ar is optionally substituted aryl; and R.sub.9 is hydroxy, alkoxy or --NR.sub.6 R.sub.7.R.sub.2 is hydrogen or acyl.R.sub.3 is C.sub.3-6 alkyl.R.sub.4 is hydrogen; alkyl; --CH.sub.2 R.sub.10 where R.sub.10 is optionally substituted phenyl or heteroaryl; or --CH(R.sub.12) O--R.sub.11 where R.sub.11 is hydrogen; alkyl; or --CH.sub.2 Ph where Ph is optionally substituted phenyl; and R.sub.12 is hydrogen or alkyl.R.sub.5 is hydrogen; alkyl; or --CH(R.sub.13) COR.sub.14 where R.sub.13 is hydrogen or alkyl; and R.sub.14 is hydroxy, alkoxy or --NR.sub.6 R.sub.7.

公开(公告)号：US4327099A

公开(公告)日：1982-04-27

申请号：US229190

申请日：1981-01-28

申请人： John M. Evans ,  Roger E. Markwell

发明人： John M. Evans ,  Roger E. Markwell

IPC分类号： A61K31/415 ,  A61P9/12 ,  C07D311/22 ,  C07D311/70 ,  C07D491/04 ,  C07D491/052 ,  C07D493/04 ,  A61K31/435 ,  C07D235/02 ,  C07D487/00

CPC分类号： C07D491/04 ,  C07D311/22 ,  C07D311/70 ,  C07D493/04

摘要： Compounds of the formula (I): ##STR1## wherein R.sub.1 and R.sub.2 are independently selected from a hydrogen atom and a C.sub.1-3 alkyl group;R.sub.3 is a hydrogen atom, a C.sub.1-3 alkyl or C.sub.2-4 acyl group;R.sub.4 is a hydrogen atom or C.sub.1-5 alkyl group;R.sub.5 is a C.sub.1-5 alkyl group, a straight chain C.sub.1-3 alkyl group terminally substituted by a chlorine atom;orR.sub.4 and R.sub.5 are joined so that together with the nitrogen atom to which they are attached they form a 5-, 6- or 7-membered ring optionally containing an oxygen or sulphur atom;R.sub.6 is a hydrogen atom, or a C.sub.1-5 alkyl, phenyl, CF.sub.3 or XH group wherein X is an oxygen or sulphur atom, the dotted line represents a bond, and R.sub.7 is not present; or R.sub.6 is an oxygen atom joined to the ring carbon atom by a double bond, the dotted line is not present, and R.sub.7 is hydrogen;the NR.sub.4 R.sub.5 and OR.sub.3 moieties are trans; and pharmaceutically acceptable salts thereof having antihypertensive activity, processes for their preparation and their use in compositions.

摘要翻译： 式（I）的化合物：其中R 1和R 2独立地选自氢原子和C 1-3烷基; R3是氢原子，C1-3烷基或C2-4酰基; R4是氢原子或C1-5烷基; R5是C1-5烷基，被氯原子末端取代的直链C1-3烷基; 或R 4和R 5连接，使得它们与它们所连接的氮原子一起形成任选含有氧或硫原子的5-，6-或7-元环; R6是氢原子或C1-5烷基，苯基，CF3或XH基，其中X是氧或硫原子，虚线表示键，R7不存在; 或R6是通过双键连接到环碳原子上的氧原子，虚线不存在，而R7是氢; NR4R5和OR3部分是反式; 其药学上可接受的盐具有抗高血压活性，其制备方法及其在组合物中的用途。

公开(公告)号：US4316899A

公开(公告)日：1982-02-23

申请号：US131237

申请日：1980-03-17

申请人： Roger E. Markwell

发明人： Roger E. Markwell

IPC分类号： C07D311/22 ,  C07D405/14 ,  A61K31/505

CPC分类号： C07D311/22

摘要： Compounds of the formula (II): ##STR1## and pharmaceutically acceptable acid-addition salts thereof wherein Ar is a pyrimidyl group having useful anti-hypertension activity, their preparation, and pharmaceutical compositions containing them.

摘要翻译： 式（II）化合物：其中Ar是具有有效抗高血压活性的嘧啶基，其制备方法和含有它们的药物组合物。

公开(公告)号：US4578393A

公开(公告)日：1986-03-25

申请号：US663232

申请日：1984-10-22

申请人： Roger E. Markwell ,  Stephen A. Smith

发明人： Roger E. Markwell ,  Stephen A. Smith

IPC分类号： C07D217/22 ,  A61K31/47 ,  A61K31/472 ,  A61P29/00 ,  A61P37/08 ,  C07D217/24 ,  C07D221/16 ,  C07D317/00 ,  C07D491/04 ,  C07D491/056

CPC分类号： C07D491/04 ,  C07D217/24 ,  C07D221/16

摘要： A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein: R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl or together are a group X which is C.sub.3-6 polymethylene optionally interrupted by O, S or NR.sub.6 wherein R.sub.6 is hydrogen or C.sub.1-6 alkyl;R.sub.3 is phenyl, optionally substituted by one or more substituents selected from halogen, CF.sub.3, nitro, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.2-7 alkanoyl, carboxyl, C.sub.1-6 alkoxycarbonyl, cyano, CONR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are selected from hydrogen or C.sub.1-6 alkyl or together are a group X; NR.sub.9 R.sub.10 wherein R.sub.9 and R.sub.10 are selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkanoyl or C.sub.1-6 alkylsulphonyl or together are a group X; SO.sub.2 NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are selected from hydrogen or C.sub.1-6 alkyl or together are a group X or S(O).sub.m R.sub.13 wherein m is 1 or 2 and R.sub.13 is C.sub.1-6 alkyl;R.sub.4 and R.sub.5 are independently selected from hydrogen, C.sub.1-6 alkyl, cyano, amino, aminocarbonyl or aminocarbamoyl optionally substituted by one or two C.sub.1-6 alkyl groups or together are a group X, halogen, CF.sub.3, nitro, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.2-7 alkanoyloxy, C.sub.1-6 alkoxy or hydroxy, or together are methylenedioxy or C.sub.3-5 polymethylene, having anti-inflammatory and/or anti-rheumatic activity, a process for their preparation and their use as pharmaceuticals.

摘要翻译： 式（I）化合物或其药学上可接受的盐：其中：R 1和R 2独立地为氢，C 1-6烷基或一起为基团X，其为任选地被O， S或NR 6，其中R 6是氢或C 1-6烷基; R3是任选被一个或多个选自卤素，CF 3，硝基，C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基，C 2-7烷酰基，羧基，C 1-6烷氧基羰基，氰基，CONR 7 R 8的取代基取代的苯基，其中 R 7和R 8选自氢或C 1-6烷基或一起为基团X; NR 9 R 10，其中R 9和R 10选自氢，C 1-6烷基，C 2-7烷酰基或C 1-6烷基磺酰基或一起为基团X; SO 2 NR 11 R 12其中R 11和R 12选自氢或C 1-6烷基或一起是基团X或S（O）m R 13，其中m为1或2，R 13为C 1-6烷基; R4和R5独立地选自氢，C1-6烷基，氰基，氨基，氨基羰基或任选被一个或两个C 1-6烷基取代的氨基氨基甲酰基，或一起是基团X，卤素，CF 3，硝基，C 1-6烷氧基， C 1-6烷硫基，C 2-7烷酰氧基，C 1-6烷氧基或羟基，或一起是具有抗炎和/或抗风湿活性的亚甲二氧基或C3-5多亚甲基，其制备方法及其作为药物的用途。

公开(公告)号：US4460594A

公开(公告)日：1984-07-17

申请号：US418267

申请日：1982-09-15

申请人： Roger E. Markwell

发明人： Roger E. Markwell

IPC分类号： C07D211/22 ,  C07D401/06 ,  C07D405/06 ,  A61K31/445 ,  C07D417/06

CPC分类号： C07D401/06 ,  C07D211/22 ,  C07D405/06

摘要： Compounds of the formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein: R.sub.1 is hydroxy, C.sub.1-4 alkoxy or an in-vivo hydrolysable acyloxy group:R.sub.2 is hydrogen, C.sub.1-4 alkyl, hydroxy, C.sub.1-4 alkoxy or an in-vivo hydrolysable acyloxy group;R.sub.4 is benzofuryl, benzothienyl, indolyl, quinolyl, isoquinolyl,2,3-dihydrobenzofuryl, 2,3-dihydrobenzylthienyl or 2,3-dihydroindolyl optionally substituted by one or two substituents selected from C.sub.1-4 alkoxy, hydroxy or acyloxy, trifluoromethyl, halogen or nitro; andA is a bond or C.sub.1-6 alkylene,a process for their preparation, and pharmaceutical compositions containing them.

摘要翻译： 式（I）化合物及其药学上可接受的盐：其中：R1是羟基，C1-4烷氧基或体内可水解的酰氧基：R2是氢，C1-4烷基，羟基， C 1-4烷氧基或体内可水解酰氧基; R4是苯并噻吩基，吲哚基，喹啉基，异喹啉基，2,3-二氢苯并呋喃基，2,3-二氢苄基噻吩基或2,3-二氢吲哚，任选地被一个或两个选自C 1-4烷氧基，羟基或酰氧基，三氟甲基，卤素 或硝基; 并且A是键或C 1-6亚烷基，其制备方法和含有它们的药物组合物。

公开(公告)号：US4925853A

公开(公告)日：1990-05-15

申请号：US290858

申请日：1988-12-28

申请人： Stephen A. Smith ,  Roger E. Markwell

发明人： Stephen A. Smith ,  Roger E. Markwell

IPC分类号： C07C205/22 ,  C07C205/23 ,  C07C205/34 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D401/06 ,  C07D405/04 ,  C07D409/04 ,  C07D409/06 ,  C07D521/00

CPC分类号： C07D231/12 ,  C07C205/22 ,  C07C205/23 ,  C07C205/34 ,  C07D233/56 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D249/08 ,  C07D401/06 ,  C07D405/04 ,  C07D409/04 ,  C07D409/06

摘要： Compounds of the general formula I ##STR1## or pharmaceutically acceptable salts or solvates thereof, in which R.sup.1 represents hydrogen or a lower alkyl group,R.sub.2 represents hydrogen, a lower alkyl group, or ##STR2## R.sup.3 represents hydrogen, a lower alkyl group, or ##STR3## R.sup.4 represents hydrogen or a lower alkyl group, R.sup.5 represents hydrogen or a lower alkyl group,R.sup.6 represents hydrogen, a lower alkyl, a substituted or unsubstituted aryl group, or --COOR.sup.15,R.sup.7 represents hydrogen, halogen or lower alkyl,R.sup.8 represents a lower alkyl or a substituted or unsubstituted carbocyclic aryl group,R.sup.15 represents hydrogen or a lower alkyl, and n is 0 to 8, n being 0 when R.sup.6 represents lower alkyl, are disclosed as an active therapeutic substances for the treatment of inflammatory conditions, allergic conditions and disorders related to loss of gastro-intestinal integrity.

摘要翻译： 通式I的化合物或其药学上可接受的盐或溶剂合物，其中R 1表示氢或低级烷基，R 2表示氢，低级烷基或R 3表示氢，低级烷基 或者，R 4表示氢或低级烷基，R 5表示氢或低级烷基，R 6表示氢，低级烷基，取代或未取代的芳基或-COOR 15，R 7表示氢，卤素或低级烷基 R8表示低级烷基或取代或未取代的碳环芳基，R15表示氢或低级烷基，n表示0〜8，R6表示低级烷基时，n表示0，作为治疗用途的活性治疗物质 炎性病症，过敏性疾病和与胃肠完整性丧失相关的疾病。

公开(公告)号：US4755525A

公开(公告)日：1988-07-05

申请号：US875350

申请日：1986-06-17

申请人： Roger E. Markwell ,  Stephen A. Smith

发明人： Roger E. Markwell ,  Stephen A. Smith

IPC分类号： A61K31/415 ,  A61K31/4184 ,  A61P1/04 ,  A61P11/00 ,  A61P27/16 ,  A61P29/00 ,  A61P37/08 ,  C07D235/10

CPC分类号： C07D235/10

摘要： A compound of the general formula I: ##STR1## or a salt or solvate thereof, in which, R.sup.1 represents hydrogen or a lower alkyl group,R.sup.2 represents hydrogen, a lower alkyl group, or ##STR2## R.sup.3 represents hydrogen, a lower alkyl group, or ##STR3## R.sup.4 represents a lower alkyl group substituted by one or more fluorine atoms,R.sup.5 represents hydrogen, halogen or lower alkyl, andR.sup.6 represents a lower alkyl or a substituted or unsubstituted carbocyclic aryl group. The compounds are useful as inhibitors of 5-lipoxygenase.

摘要翻译： 通式I的化合物或其盐或溶剂合物，其中R 1表示氢或低级烷基，R 2表示氢，低级烷基或R 3表示氢， 低级烷基，或者R 4表示被一个或多个氟原子取代的低级烷基，R 5表示氢，卤素或低级烷基，R 6表示低级烷基或取代或未取代的碳环芳基。 该化合物可用作5-脂氧合酶的抑制剂。

公开(公告)号：US4745115A

公开(公告)日：1988-05-17

申请号：US789105

申请日：1985-10-18

申请人： Roger E. Markwell ,  Stephen A. Smith ,  David J. Hunter

发明人： Roger E. Markwell ,  Stephen A. Smith ,  David J. Hunter

IPC分类号： A61K31/435 ,  A61K31/47 ,  A61K31/472 ,  A61K31/473 ,  A61P29/00 ,  A61P37/08 ,  C07D217/22 ,  C07D217/24 ,  C07D221/08 ,  C07D221/10 ,  C07D401/04

CPC分类号： C07D401/04 ,  C07D217/22 ,  C07D217/24 ,  C07D221/08 ,  C07D221/10

摘要： Compounds of the general formula I ##STR1## in which: R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl or together are a group X which is C.sub.3-6 polymethylene optionally in which one carbon atom is replaced by O, S or NR.sub.6 wherein R.sub.6 is hydrogen or C.sub.1-6 alkyl;R.sub.3 is a mono- or fused bi-cyclic heteroaromatic group having up to ten atoms in the aromatic ring(s), not more than four of which are selected from nitrogen, oxygen or sulphur, optionally C-substituted by one or more substituents selected from halogen, CF.sub.3, nitro, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.2-7 alkanoyl or cyano; or is phenyl or naphthyl, optionally substituted by one or more substituents selected from halogen, CF.sub.3, nitro, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.2-7 alkanoyl, carboxyl, C.sub.1-6 alkoxycarbonyl, cyano, CONR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are selected from hydrogen or C.sub.1-6 alkyl or together are a group X; NR.sub.9 R.sub.10 wherein R.sub.9 and R.sub.10 are selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkanoyl or C.sub.1-6 alkylsulphonyl or together are a group X; SO.sub.2 NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are selected from hydrogen or C.sub.1-6 alkyl or together are a group X; or S(O).sub.m R.sub.13 wherein m is 1 or 2 and R.sub.13 is C.sub.1-6 alkyl; Z is naphthyl or a mono- or fused bicyclic heteroaromatic ring having up to ten atoms in the aromatic ring(s), not more than four of which are selected from nitrogen, oxygen or sulphur or (when R.sub.3 is an optionally substituted naphthyl or heteroaromatic group as defined) Z is a phenyl ring; and Z is optionally C-substituted by one or two substituents R.sub.4 and R.sub.5 which are independently selected from C.sub.1-6 alkyl, cyano, amino, aminocarbonyl or aminocarbamoyl optionally substituted by one or two C.sub.1-6 alkyl groups or by a group X, halogen, CF.sub.3, nitro, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.2-7 alkanoyloxy or hydroxy, or together on adjacent carbon atoms are methylenedioxy or C.sub.3-5 polymethylene,are disclosed as an active therapeutic substances for the treatment of inflammatory conditions.

公开(公告)号：US4428940A

公开(公告)日：1984-01-31

申请号：US356445

申请日：1982-03-09

申请人： Roger E. Markwell

发明人： Roger E. Markwell

IPC分类号： C07D417/12 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/425 ,  A61K38/00 ,  A61P9/12 ,  A61P43/00 ,  C07D307/79 ,  C07D307/80 ,  C07D405/12 ,  C07D409/06 ,  C07K5/02 ,  A61K37/00 ,  A01N43/78

CPC分类号： C07D307/79 ,  C07D307/80 ,  C07K5/0222 ,  A61K38/00

摘要： Compounds of formula (I): ##STR1## or a pharmaceutically acceptable salt thereof, wherein m is 0 to 3;n is 1 to 5;R.sub.1 is hydrogen, or C.sub.1-6 alkyl;R.sub.2 is hydrogen, C.sub.1-4 alkyl, --(CH.sub.2).sub.p --NH.sub.2wherein p is 1 to 4, or --NHCOR, wherein R.sub.5 is C.sub.1-4 alkyl;R.sub.3 is hydrogen or C.sub.1-6 alkyl;R.sub.4 is C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or CF.sub.3 ; and X is CH.sub.2 or S.having useful pharmacological activity, compositions containing them, and a process for their preparation.

摘要翻译： 式（I）化合物：其中m为0至3;或其药学上可接受的盐，其中m为0至3; n为1至5; R1是氢或C1-6烷基; R2是氢，C1-4烷基， - （CH2）p-NH2，其中p是1至4，或-NHCOR，其中R5是C1-4烷基; R3是氢或C1-6烷基; R4是C1-4烷基，C1-4烷氧基，卤素或CF3; 并且X是具有有用药理活性的CH2或S.，含有它们的组合物及其制备方法。