公开(公告)号：US4833136A

公开(公告)日：1989-05-23

申请号：US8267

申请日：1987-01-29

申请人： Roger E. Markwell ,  Robert W. Ward ,  Carol R. De Mello

发明人： Roger E. Markwell ,  Robert W. Ward ,  Carol R. De Mello

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： A compound of the formula (I) or a salt or solvate thereof: ##STR1## in which: R.sub.0 is hydrogen or C.sub.1-6 alkyl; or together with R.sub.3 is C.sub.4-6 polymethylene;R.sub.1 and R.sub.2 are both hydrogen; orR.sub.1 is hydrogen, C.sub.1-6 alkyl; and R.sub.2 is CN; CR.sub.5 R.sub.6 Y where R.sub.5 and R.sub.6 are independently selected from hydrogen and C.sub.1-4 alkyl and Y is selected from hydrogen, OR.sub.7 or SR.sub.7 where R.sub.7 is hydrogen, C.sub.1-4 alkyl or C.sub.2-4 alkanoyl, and NR.sub.8 R.sub.9 where R.sub.8 and R.sub.9 are independently hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkanoyl or together are C.sub.4-6 polymethylene; or COR.sub.10 where R.sub.10 is OH or C.sub.1-4 alkyl, or COR.sub.10 is a pharmaceutically acceptable ester or amide, orR.sub.2 is hydrogen, C.sub.1-6 alkyl, or phenyl optionally substituted by halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl, and R.sub.1 is CN, CR.sub.5 R.sub.6 Y or COR.sub.10 as defined for R.sub.2 above; orR.sub.1 and R.sub.2 together form C.sub.3 -C.sub.6 polymethylene optionally substituted by C.sub.1 -C.sub.4 alkyl;R.sub.3 is hydrogen; or C.sub.1-10 alkyl or C.sub.3-10 cycloalkyl, either optionally substituted by hydroxy, C.sub.1-4 alkoxy, thiol, C.sub.1-4 alkylthio or NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are independently hydrogen, C.sub.1-6 alkyl or C.sub.2-7 alkanoyl or together are C.sub.3-6 polymethylene; C.sub.2-10 alkenyl; or phenyl optionally substituted by one or two of halogen, CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, hydroxy, nitro, cyano, C.sub.2-10 acyloxy, NR.sub.13 R.sub.14 wherein R.sub.13 and R.sub.14 are independently selected from hydrogen, C.sub.1-6 alkyl, or C.sub.2-7 alkanoyl; or COR.sub.15 wherein R.sub.15 is hydroxy, C.sub.1-6 alkoxy or NR.sub.16 R.sub.17 wherein R.sub.16 and R.sub.17 are independently selected from hydrogen or C.sub.1-6 alkyl; orR.sub.3 is a mono- or fused bi-cyclic heteroaryl group having up to ten atoms in the aromatic ring(s), not more than two of which are selected from nitrogen, oxygen or sulphur, other than those containing basic nitrogen, optionally substituted by one or two substituents selected from halogen, CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, hydroxy, nitro, cyano, C.sub.2-10 acyloxy, NR.sub.23 R.sub.24 wherein R.sub.23 and R.sub.24 are independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkanoyl or C.sub.1-6 alkylsulphonyl; or COR.sub.25 wherein R.sub.25 is hydroxy, C.sub.1-6 alkoxy or NR.sub.26 R.sub.27 wherein R.sub.26 and R.sub.27 are independently selected from hydrogen or C.sub.1-6 alkyl;R.sub.4 is hydrogen, or C.sub.1-4 alkyl, phenyl or benzyl, each of which is optionally substituted in the phenyl ring by one or two of halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl and is attached at nitrogen atom 1 or 2; andR.sub.x is C.sub.1-6 alkyl, halogen, nitro, NR.sub.18 R.sub.19 where R.sub.18 and R.sub.19 are independently hydrogen, C.sub.1-6 alkyl or C.sub.2-7 alkanoyl, nitrile, COOH, CONH.sub.2 ; phenyl or benzyl optionally substituted by one or two of halogen, nitro, C.sub.1-6 alkoxy, hydroxy, C.sub.2-7 alkanoyloxy, NR.sub.18 R.sub.19, C.sub.1-6 alkyl, CF.sub.3, CN; thienyl, furyl or pyrryl optinoally N-substituted by C.sub.1-6 alkyl,with the proviso that R.sub.0 and R.sub.3 are not both hydrogen when R.sub.1 is hydrogen and R.sub.2 and R.sub.x are methyl, is useful for treating inflammatory or allergic conditions.

公开(公告)号：US4716160A

公开(公告)日：1987-12-29

申请号：US856454

申请日：1986-04-25

申请人： Roger E. Markwell ,  Robert W. Ward ,  Carol R. de Mello

发明人： Roger E. Markwell ,  Robert W. Ward ,  Carol R. de Mello

IPC分类号： A61K31/44 ,  C07D471/04

CPC分类号： C07D471/04

摘要： Compounds of formula (I) ##STR1## wherein: R is hydrogen or C.sub.1-6 alkyl;R.sub.1 and R.sub.2 are both hydrogen; orR.sub.1 is hydrogen, C.sub.1-6 alkyl; and R.sub.2 is CN; CR.sub.5 R.sub.6 Y where R.sub.5 and R.sub.6 are independently selected from hydrogen and C.sub.1-4 alkyl and Y is selected from hydrogen, OR.sub.7 or SR.sub.7 where R.sub.7 is hydrogen, C.sub.1-4 alkyl or C.sub.2-4 alkanoyl, and NR.sub.8 R.sub.9 where R.sub.8 and R.sub.9 are independently hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkanoyl or together are C.sub.4-6 polymethylene, or COR.sub.10 where R.sub.10 is OH or C.sub.1-4 alkyl, or COR.sub.10 is a pharmaceutically acceptable ester or amide; orR.sub.2 is hydrogen, C.sub.1-6 alkyl, or phenyl optionally substituted by halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl; and R.sub.1 is CN, CR.sub.5 R.sub.6 Y or COR.sub.10 as defined for R.sub.2 above; orR.sub.1 and R.sub.2 together form C.sub.3 -C.sub.6 polymethylene optionally substituted by C.sub.1 -C.sub.4 alkyl;R.sub.3 a mono- or fused bi-cyclic heteroaryl group having up to ten atoms in the aromatic ring(s), not more than two of which are selected from nitrogen, oxygen or sulphur, other than those containing basic nitrogen, optionally substituted by one or two substituents selected from halogen, CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, hydroxy, nitro, cyano, C.sub.2-10 acyloxy, NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkanoyl or C.sub.1-6 alkylsulphonyl; or COR.sub.13 wherein R.sub.13 is hydroxy, C.sub.1-6 alkoxy or NR.sub.14 R.sub.15 wherein R.sub.15 and R.sub.14 are independently selected from hydrogen or C.sub.1-6 alkyl; andR.sub.4 is hydrogen, or C.sub.1-4 alkyl, or benzyl optionally substituted in the phenyl ring by one or more of halogen, CF.sub.3, C.sub.1-4 alkyl, and is attached at nitrogen atom 1 or 2; show anti-inflammatory and anti-allergy activity.

摘要翻译： 式（I）化合物其中：R是氢或C 1-6烷基; R1和R2都是氢; 或R 1为氢，C 1-6烷基; R2为CN; CR5R6Y，其中R5和R6独立地选自氢和C1-4烷基，Y选自氢，OR7或SR7，其中R7是氢，C1-4烷基或C2-4烷酰基，和NR8R9，其中R8和R9独立地是氢， C 1-4烷基，C 2-4链烯基或C 2-4烷酰基或一起是C 4-6多亚甲基或COR 10，其中R 10是OH或C 1-4烷基，或COR 10是药学上可接受的酯或酰胺; 或R 2为氢，C 1-6烷基或任选被卤素，CF 3，C 1-4烷氧基或C 1-4烷基取代的苯基; 并且R 1是如上定义的CN，CR 5 R 6 Y或COR 10; 或R 1和R 2一起形成任选被C 1 -C 4烷基取代的C 3 -C 6聚亚甲基; R3是在芳环中具有至多10个原子的单或稠合双环杂芳基，其中不超过两个选自氮，氧或硫，除了含有碱性氮的那些，任选被一个 或选自卤素，CF 3，C 1-4烷氧基，C 1-4烷基，羟基，硝基，氰基，C 2-10酰氧基，NR 11 R 12中的两个取代基，其中R 11和R 12独立地选自氢，C 1-6烷基，C 2-7 烷酰基或C 1-6烷基磺酰基; 或COR 13，其中R 13是羟基，C 1-6烷氧基或NR 14 R 15，其中R 15和R 14独立地选自氢或C 1-6烷基; R 4是氢或C 1-4烷基，或在苯环中被一个或多个卤素，CF 3，C 1-4烷基取代的苄基，并且在氮原子1或2上连接; 显示抗炎和抗过敏活性。

公开(公告)号：US4935404A

公开(公告)日：1990-06-19

申请号：US270085

申请日：1988-11-14

申请人： David J. Hunter ,  Roger E. Markwell ,  Robert W. Ward

发明人： David J. Hunter ,  Roger E. Markwell ,  Robert W. Ward

IPC分类号： A61K38/55 ,  A61K38/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07F9/30 ,  C07F9/38 ,  C07F9/40 ,  C07F9/572 ,  C07K5/06

CPC分类号： C07F9/4006 ,  C07K5/06191 ,  A61K38/00

摘要： Novel compounds of the formula (I), a process for their preparation and their use as collagenase inhibitors are described: ##STR1## in which R.sub.1 is hydrogen or hydroxy; R.sub.2 is hydrogen or alkyl; R.sub.3 is C.sub.3-6 alkyl; R.sub.4 is hydrogen, alkyl, --CH.sub.2 --Z where Z is optionally substituted phenyl or heteroaryl, or R.sub.4 is a group ##STR2## where R.sub.8 is hydrogen, alkyl or --CH.sub.2 --Ph where Ph is optionally substituted phenyl, and R.sub.9 is hydrogen or alkyl; and R.sub.5 is hydrogen or alkyl.

公开(公告)号：US4837238A

公开(公告)日：1989-06-06

申请号：US112050

申请日：1987-10-21

申请人： Roger E. Markwell ,  Ian Hughes ,  Robert W. Ward

发明人： Roger E. Markwell ,  Ian Hughes ,  Robert W. Ward

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： Compounds of the formula (I): ##STR1## wherein: X is NR wherein R is hydrogen, C.sub.1-6 alkyl; oxygen; sulphur; SO; or SO.sub.2 ; or R and R.sub.3 taken together are C.sub.4-6 polymethylene;R.sub.1 is hydrogen or C.sub.1-6 alkyl; and R.sub.2 is CN, CR.sub.5 R.sub.6 Y where R.sub.5 and R.sub.6 are independently selected from hydrogen and C.sub.1-4 alkyl and Y is selected from hydrogen, OR.sub.7 or SR.sub.7 where R.sub.7 is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkanoyl, and NR.sub.8 R.sub.9 where R.sub.8 and R.sub.9 are independently hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkanoyl or R.sub.8 and R.sub.9 together are C.sub.4-6 polymethylene, or COR.sub.10 where R.sub.10 is C.sub.1-4 alkyl, provided that Y is other than hydrogen when R.sub.1 is hydrogen;orR.sub.2 is hydrogen C.sub.1-6 alkyl or phenyl optionally substituted by halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl; and R.sub.1 is CN, CR.sub.5 R.sub.6 Y or COR.sub.10 as defined for R.sub.2 above;orR.sub.1 and R.sub.2 together form C.sub.3 -C.sub.6 polymethylene optionally substituted by C.sub.1 -C.sub.4 alkyl;R.sub.3 is C.sub.1-10 alkyl or C.sub.3-10 cycloalkyl, either optionally substituted by hydroxy, C.sub.1-4 alkoxy, thiol, C.sub.1-4 alkylthio or NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are independently hydrogen, C.sub.1-6 alkyl or C.sub.2-7 alkanoyl or together are C.sub.3-6 polymethylene; C.sub.2-10 alkenyl; or phenyl optionally substituted by one or two of halogen, CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, hydroxy, nitro, cyano, C.sub.2-10 acyloxy, NR.sub.13 R.sub.14 wherein R.sub.13 and R.sub.14 are independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-7 alkanoyl, C.sub.1-6 alkylsulphonyl or COR.sub.15 wherein R.sub.15 is hydroxy, C.sub.1-6 alkoxy or NR.sub.16 R.sub.17 wherein R.sub.16 and R.sub.17 are independently selected from hydrogen or C.sub.1-6 alkyl; or together with R is C.sub.4-6 polymethylene; andR.sub.4 is hydrogen; or C.sub.1-4 alkyl or benzyl optionally substituted in the phenyl ring by one or two of halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl and is attached at nitrogen atom 1 or 2, are disclosed as having utility in the treatment of inflammatory and allergic disorders.

摘要翻译： 式（I）的化合物：其中：X是NR，其中R是氢，C 1-6烷基; 氧; 硫; 所以; 或SO2; 或R和R3一起为C4-6聚亚甲基; R1是氢或C1-6烷基; 并且R 2是CN，CR 5 R 6 Y，其中R 5和R 6独立地选自氢和C 1-4烷基，Y选自氢，OR 7或SR 7，其中R 7是氢，C 1-4烷基，C 2-4烷酰基和NR 8 R 9，其中R 8和 R 9独立地是氢，C 1-4烷基，C 2-4烯基或C 2-4烷酰基，或者R 8和R 9一起是C 4-6多亚甲基，或COR 10，其中R 10是C 1-4烷基，条件是Y不是氢，当R 1是 氢; 或R 2为氢或C 1-6烷基或任选被卤素，CF 3，C 1-4烷氧基或C 1-4烷基取代的苯基; 并且R 1是如上定义的CN，CR 5 R 6 Y或COR 10; 或R 1和R 2一起形成任选被C 1 -C 4烷基取代的C 3 -C 6聚亚甲基; R3是C1-10烷基或C3-10环烷基，任选被羟基，C 1-4烷氧基，硫醇，C 1-4烷硫基或NR 11 R 12取代，其中R 11和R 12独立地是氢，C 1-6烷基或C 2-7烷酰基或一起 是C3-6聚亚甲基; C 2-10烯基; 或任选被一个或两个卤素，CF 3，C 1-4烷氧基，C 1-4烷基，羟基，硝基，氰基，C 2-10酰氧基，NR 13 R 14取代的苯基，其中R 13和R 14独立地选自氢，C 1-6烷基， C 2-6烷酰基，C 1-6烷基磺酰基或COR 15，其中R 15是羟基，C 1-6烷氧基或NR 16 R 17，其中R 16和R 17独立地选自氢或C 1-6烷基; 或与R一起为C4-6聚亚甲基; R4为氢; 或在苯环中被卤素，CF 3，C 1-4烷氧基或C 1-4烷基中的一个或两个取代的C 1-4烷基或苄基，并且在氮原子1或2上连接，被公开用于治疗 炎性和过敏性疾病。

公开(公告)号：US4670432A

公开(公告)日：1987-06-02

申请号：US852152

申请日：1986-04-15

申请人： Robert W. Ward ,  Roger E. Markwell

发明人： Robert W. Ward ,  Roger E. Markwell

IPC分类号： A61K31/435 ,  A61P29/00 ,  A61P37/08 ,  C07D231/16 ,  C07D231/38 ,  C07D471/04 ,  A61K31/44

CPC分类号： C07D231/38 ,  C07D231/16 ,  C07D471/04

摘要： A compound of formula (I) or a salt thereof: ##STR1## wherein: R.sub.1 is hydrogen, C.sub.1-6 alkyl or phenyl optionally substituted by halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl;R.sub.2 is hydrogen or C.sub.1-6 alkyl;R.sub.3 is C.sub.2-10 alkenyl or C.sub.1-10 alkyl substituted by hydroxy, C.sub.1-4 alkoxy, thiol, C.sub.1-4 alkylthio or NR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are independently hydrogen or C.sub.1-6 alkyl or together are C.sub.3-6 polymethylene;R.sub.4 and R.sub.5 are independently hydrogen or C.sub.1-4 alkyl; andR.sub.6 is hydrogen; or C.sub.1-4 alkyl or benzyl attached at nitrogen atom 1 or 2;having anti-inflammatory and/or anti-allergy activity.

摘要翻译： 式（I）化合物或其盐：其中：R 1是氢，任选地被卤素，CF 3，C 1-4烷氧基或C 1-4烷基取代的C 1-6烷基或苯基; R2是氢或C1-6烷基; R3是C2-10烯基或被羟基，C1-4烷氧基，硫醇，C1-4烷硫基或NR7R8取代的C1-10烷基，其中R7和R8独立地是氢或C1-6烷基或一起是C3-6聚亚甲基; R4和R5独立地是氢或C1-4烷基; R6是氢; 或在氮原子1或2连接的C 1-4烷基或苄基; 具有抗炎和/或抗过敏活性。

公开(公告)号：US5212163A

公开(公告)日：1993-05-18

申请号：US758356

申请日：1991-09-09

申请人： Robert W. Ward ,  Roger E. Markwell ,  David J. Hunter

发明人： Robert W. Ward ,  Roger E. Markwell ,  David J. Hunter

IPC分类号： C07F9/38 ,  C07F9/40 ,  C07F9/553 ,  C07F9/572 ,  C07K5/06 ,  C07K5/08

CPC分类号： C07F9/3808 ,  C07F9/4006 ,  C07F9/5532 ,  C07F9/5728 ,  C07K5/06191 ,  C07K5/0827

摘要： Novel compounds of formula (I) and salts, solvates and hydrates thereof, processes for their preparation and their use in the treatment of conditions in which degradation of connective tissue and other proteinaceous components of the body occurs: ##STR1## in which, R is hydrogen, C.sub.1-6 alkyl or optionally substituted benzyl; R.sub.1 is hydrogen or C.sub.1-6 alkyl; R.sub.2 is C.sub.3-6 alkyl; R.sub.3 is hydrogen, alkyl, --CH.sub.2 --Z where Z is optionally substituted phenyl or heteroaryl, or R.sub.3 is a group ##STR2## where R.sub.7 is hydrogen, alkyl or --CH.sub.2 --Ph where Ph is optionally substituted phenyl and R.sub.8 is hydrogen or alkyl; and R.sub.4 is --CH.sub.2 --(CH.sub.2).sub.n OR.sub.5 or --CH.sub.2 --(CH.sub.2).sub.n OCOR.sub.6 or --CH(R.sub.9)COR.sub.10, where n is an integer from 1 to 6; R.sub.5, R.sub.6 and R.sub.9 are hydrogen or C.sub.1-6 alkyl; and R.sub.10 is hydroxy or --O--C.sub.1-6 alkyl or --NR.sub.5 R.sub.6 (where R.sub.5 and R.sub.6 may be linked to form a heterocyclic ring; or R.sub.3 and R.sub.4 are joined together as --(CH.sub.2).sub.m -- where m is an integer from 4 to 12.

摘要翻译： 式（I）的新型化合物及其盐，溶剂化物和水合物，其制备方法及其用于治疗结缔组织和身体其它蛋白质成分降解的病症发生：其中（I） ，R为氢，C 1-6烷基或任选取代的苄基; R1是氢或C1-6烷基; R2是C3-6烷基; R3是氢，烷基，-CH2-Z，其中Z是任选取代的苯基或杂芳基，或R3是基团，其中R7是氢，烷​​基或-CH2-Ph，其中Ph是任选取代的苯基，R8是氢或烷基 ; 并且R 4是-CH 2 - （CH 2）nOR 5或-CH 2 - （CH 2）nOCOR 6或-CH（R 9）COR 10，其中n是1至6的整数; R5，R6和R9是氢或C1-6烷基; 并且R 10是羟基或-O-C 1-6烷基或-NR 5 R 6（其中R 5和R 6可以连接形成杂环;或者R 3和R 4连接在一起作为 - （CH 2）m - ，其中m是4的整数 到12岁

公开(公告)号：US4818754A

公开(公告)日：1989-04-04

申请号：US39540

申请日：1987-04-16

申请人： Robert W. Ward ,  Roger E. Markwell ,  Ian Hughes

发明人： Robert W. Ward ,  Roger E. Markwell ,  Ian Hughes

IPC分类号： A61K31/435 ,  A61P29/00 ,  A61P37/08 ,  C07D471/04

CPC分类号： C07D471/04

摘要： A compound of the formula (1) or a salt or solvate thereof: ##STR1## in which: R.sub.0 is hydrogen or C.sub.1-6 alkyl;R.sub.1 and R.sub.2 are both hydrogen; orR.sub.1 is hydrogen, C.sub.1-6 alkyl; and R.sub.2 is CN; CR.sub.5 R.sub.6 Y where R.sub.5 and R.sub.6 are independently selected from hydrogen and C.sub.1-4 alkyl and Y is selected from hydrogen, OR.sub.7 or SR.sub.7 where R.sub.7 is hydrogen, C.sub.1-4 alkyl or C.sub.2-4 alkanoyl, and NR.sub.8 R.sub.9 where R.sub.8 and R.sub.9 are independently hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkanoyl or together are C.sub.4-6 polymethylene; or COR.sub.10 is OH or C.sub.1-4 alkyl, or COR.sub.10 is a pharmaceutically acceptable ester or amide; orR.sub.2 is hydrogen, C.sub.1-6 alkyl, or phenyl optionally substituted by halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl; and R.sub.1 is CN, CR.sub.5 R.sub.6 Y or COR.sub.10 as defined for R.sub.2 above; orR.sub.1 and R.sub.2 together form C.sub.3 -C.sub.6 polymethylene optionally substituted by C.sub.1 -C.sub.4 alkyl;R.sub.3 is --(CH.sub.2).sub.n CO.sub.2 R.sub.11, --(CH.sub.2).sub.n CONR.sub.12 R.sub.13,--(CH.sub.2).sub.n CN, --(CH.sub.2).sub.m NHCOR.sub.14, ##STR2## where a, b, n, m and p are integers and n is 1 to 10, m is 2 to 10, p is 3 to 5, a is 1 to 3, and b is 1 to 3,and R.sub.11 is hydrogen, C.sub.1-8 alkyl, benzyl or phenyl, R.sub.12 and R.sub.13 are independently hydrogen, C.sub.1-6 alkyl, benzyl or phenyl, or together form C.sub.3-8 alkylene, R.sub.14 is C.sub.1-4 alkyl, benzyl or phenyl and X is oxygen, sulphur, NH or N--C.sub.1-4 alkyl, andR.sub.4 is hydrogen; or C.sub.1-4 alkyl or benzyl optionally substituted in the phenyl ring by one or two of halogen, CF.sub.3, C.sub.1-4 alkoxy or C.sub.1-4 alkyl, and is attached at nitrogen atom 1 or 2, a process for its preparation and its use as a pharmaceutical.

摘要翻译： 式（1）的化合物或其盐或溶剂化物：其中：R 0是氢或C 1-6烷基; R1和R2都是氢; 或R 1为氢，C 1-6烷基; R2为CN; CR5R6Y，其中R5和R6独立地选自氢和C1-4烷基，Y选自氢，OR7或SR7，其中R7是氢，C1-4烷基或C2-4烷酰基，和NR8R9，其中R8和R9独立地是氢， C 1-4烷基，C 2-4烯基或C 2-4烷酰基或一起是C 4-6多亚甲基; 或COR 10是OH或C 1-4烷基，或COR 10是药学上可接受的酯或酰胺; 或R 2为氢，C 1-6烷基或任选被卤素，CF 3，C 1-4烷氧基或C 1-4烷基取代的苯基; 并且R 1是如上定义的CN，CR 5 R 6 Y或COR 10; 或R 1和R 2一起形成任选被C 1 -C 4烷基取代的C 3 -C 6聚亚甲基; R3是 - （CH2）nCO2R11， - （CH2）nCONR12R13， - （CH2）nCN， - （CH2）mNHCOR14， 其中a，b，n，m和p是整数，n是1到10 m为2至10，p为3至5，a为1至3，b为1至3，R 11为氢，C 1-8烷基，苄基或苯基，R 12和R 13独立地为氢，C 1-6 烷基，苄基或苯基，或一起形成C 3-8亚烷基，R 14是C 1-4烷基，苄基或苯基，X是氧，硫，NH或N-C 1-4烷基，R 4是氢; 或任选在苯环中被卤素，CF 3，C 1-4烷氧基或C 1-4烷基中的一个或两个取代的C 1-4烷基或苄基，并且在氮原子1或2上连接，其制备方法及其用途 作为药物。

公开(公告)号：US4548948A

公开(公告)日：1985-10-22

申请号：US581440

申请日：1984-02-17

申请人： Robert W. Ward ,  Stephen A. Smith ,  Roger E. Markwell

发明人： Robert W. Ward ,  Stephen A. Smith ,  Roger E. Markwell

IPC分类号： A61K31/38 ,  C07C45/46 ,  C07C45/63 ,  C07C49/784 ,  C07C63/04 ,  C07D307/84 ,  C07D307/85 ,  C07D307/87 ,  C07D311/22 ,  C07D333/54 ,  C07D333/56 ,  C07D333/68 ,  C07D409/06 ,  C07F7/18 ,  A61K31/34 ,  A61K31/40 ,  C07D333/38

CPC分类号： C07D333/54 ,  C07C323/00 ,  C07C45/46 ,  C07C45/63 ,  C07C49/784 ,  C07C63/04 ,  C07D307/84 ,  C07D307/85 ,  C07D311/22 ,  C07D333/56 ,  C07D333/68 ,  C07D409/06 ,  C07F7/1852

摘要： Compounds of formula (I): ##STR1## wherein: Ar is phenyl optionally substituted in the o-, m- or p-position by C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trifluoromethyl, bromo, chloro or fluoro,pyrryl optionally N-substituted by C.sub.1-4 alkyl,2-furyl or 2-thienyl either optionally substituted in the 3-, 4- or 5-position by methyl, chloro or bromo, or3-furyl or 3-thienyl;X is oxygen, sulphur, sulphoxide or sulphone, Y is methylene, R.sub.1 and R.sub.3 are hydrogen or C.sub.1-4 alkyl, and R.sub.2 is hydrogen, C.sub.1-4 alkyl, fluoro, chloro or bromo, or X is methylene, Y is oxygen, R.sub.1 and R.sub.3 are both hydrogen, and R.sub.2 is hydrogen, fluoro, chloro or bromo; andR.sub.4 is hydrogen or C.sub.1-4 alkyl, or a salt thereof, have analgesic and/or anti-inflammatory activity.

摘要翻译： 式（I）化合物：其中：Ar是任选地被C 1-4烷基，C 1-4烷氧基，三氟甲基，溴，氯或氟取代在邻位，间或对位的苯基， 任选被C1-4烷基，2-呋喃基或2-噻吩取代的吡咯基，其任选在3-，4-或5-位被甲基，氯或溴或3-呋喃基或3-噻吩基取代; X是氧，硫，亚砜或砜，Y是亚甲基，R 1和R 3是氢或C 1-4烷基，R 2是氢，C 1-4烷基，氟，氯或溴，或X是亚甲基，Y是氧， R1和R3都是氢，R2是氢，氟，氯或溴; R4为氢或C1-4烷基或其盐具有止痛和/或消炎活性。

公开(公告)号：US5010097A

公开(公告)日：1991-04-23

申请号：US287453

申请日：1988-12-20

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

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

IPC分类号： C07D209/18 ,  A61K31/16 ,  A61K31/165 ,  A61K31/195 ,  A61K31/22 ,  A61K31/335 ,  A61K31/357 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K38/55 ,  A61P1/02 ,  A61P17/00 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C319/02 ,  C07C323/41 ,  C07C323/60 ,  C07C327/04 ,  C07C327/16 ,  C07C327/32 ,  C07D317/22 ,  C07D317/30 ,  C07K1/113 ,  C07K5/06 ,  C07K14/81

CPC分类号： C07C323/60 ,  C07C327/32 ,  C07D317/22 ,  C07D317/30

摘要： Novel compounds of the formula (I), a process for their preparation and their use as collagenase inhibitors are described: ##STR1## in which, R.sub.1 is hydrogen, alkyl, or optionally substituted aryl;R.sub.2 is hydrogen, or acyl such as ##STR2## where Z is optionally substituted aryl; 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 a group ##STR3## 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; andR.sub.5 is hydrogen, alkyl, or a group ##STR4## where R.sub.13 is hydrogen, or alkyl, and R.sub.14 is hydroxy, alkoxy, or --NR.sub.6 R.sub.7, where each of R.sub.6 and R.sub.7 is hydrogen or alkyl, or R.sub.6 and R.sub.7 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-membered ring with an optional oxygen or sulphur atom in the ring or an optional further nitrogen atom optionally substituted by alkyl.

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。