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1. 发明授权

US5447929A Method of treating joint disorders using hydroxamic derivatives 失效
标题翻译：使用异羟肟酸衍生物治疗关节疾病的方法
公开(公告)号：US5447929A
公开(公告)日：1995-09-05
申请号：US214895
申请日：1994-03-17
申请人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
发明人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
IPC分类号： A61K31/40 , A61K20060101 , A61K31/16 , A61K31/165 , A61K31/395 , A61K31/4015 , A61K31/403 , A61K31/4035 , A61K31/404 , A61K31/415 , A61K31/4166 , A61K31/4245 , A61K31/425 , A61K31/4427 , A61K31/445 , A61K31/495 , A61K31/496 , A61K31/50 , A61K31/53 , A61K31/535 , A61K31/536 , A61K31/5375 , A61K31/5377 , A61K31/54 , A61K31/55 , A61K33/08 , A61K38/00 , A61P9/10 , A61P29/00 , A61P35/00 , A61P43/00 , C07C20060101 , C07C259/10 , C07C317/44 , C07C323/04 , C07C333/24 , C07D20060101 , C07D207/26 , C07D207/27 , C07D207/40 , C07D207/404 , C07D207/408 , C07D209/18 , C07D209/48 , C07D211/88 , C07D233/72 , C07D233/74 , C07D233/96 , C07D239/52 , C07D239/54 , C07D239/88 , C07D249/12 , C07D253/06 , C07D271/06 , C07D271/07 , C07D295/18 , C07D401/06 , C07D401/12 , C07D403/06 , C07D403/12 , C07D407/06 , C07D413/06 , C07D413/12 , C07D417/06 , C07D417/12 , C07D491/10 , C07D491/113 , C07K5/06 , C07K5/10 , C12N9/99
CPC分类号： C07D207/27 , C07D207/404 , C07D209/48 , C07D211/88 , C07D233/74 , C07D249/12 , C07D271/07 , C07D401/06 , C07D401/12 , C07D403/06 , C07D403/12 , C07D417/06 , C07D491/10
摘要： Hydroxamic acid derivatives of the fdrrnula ##STR1## and pharmaceutically acceptable salts thereof, which are collagenase inhibitors useful for the control or prevention of degenerative joint diseases, such as, rheumatoid arthritis and ostecarthritis or for the treatment of invasive tumours, atherosclerosis or multiple sclerosis, are described. Said compounds can be prepared either by hyclroxamidating a corresponding carboxylic acid or deprotecting a corresponding benzyloxycarbamoyl compound.
摘要翻译：可以用于控制或预防退行性关节疾病例如类风湿性关节炎和骨关节炎或用于治疗侵入性肿瘤的胶原酶抑制剂，动脉粥样硬化或其它药学上可接受的盐，多发性硬化症。所述化合物可以通过将相应的羧酸环烷酰胺化或者使相应的苄氧基氨基甲酰基化合物脱保护来制备。

2. 发明授权

US5318964A Hydroxamic derivatives and pharmaceutical compositions 失效
标题翻译：羟肟酸衍生物和药物组合物
公开(公告)号：US5318964A
公开(公告)日：1994-06-07
申请号：US066832
申请日：1993-05-24
申请人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
发明人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
IPC分类号： A61K31/40 , A61K20060101 , A61K31/16 , A61K31/165 , A61K31/395 , A61K31/4015 , A61K31/403 , A61K31/4035 , A61K31/404 , A61K31/415 , A61K31/4166 , A61K31/4245 , A61K31/425 , A61K31/4427 , A61K31/445 , A61K31/495 , A61K31/496 , A61K31/50 , A61K31/53 , A61K31/535 , A61K31/536 , A61K31/5375 , A61K31/5377 , A61K31/54 , A61K31/55 , A61K33/08 , A61K38/00 , A61P9/10 , A61P29/00 , A61P35/00 , A61P43/00 , C07C20060101 , C07C259/10 , C07C317/44 , C07C323/04 , C07C333/24 , C07D20060101 , C07D207/26 , C07D207/27 , C07D207/40 , C07D207/404 , C07D207/408 , C07D209/18 , C07D209/48 , C07D211/88 , C07D233/72 , C07D233/74 , C07D233/96 , C07D239/52 , C07D239/54 , C07D239/88 , C07D249/12 , C07D253/06 , C07D271/06 , C07D271/07 , C07D295/18 , C07D401/06 , C07D401/12 , C07D403/06 , C07D403/12 , C07D407/06 , C07D413/06 , C07D413/12 , C07D417/06 , C07D417/12 , C07D491/10 , C07D491/113 , C07K5/06 , C07K5/10 , C12N9/99
CPC分类号： C07D207/27 , C07D207/404 , C07D209/48 , C07D211/88 , C07D233/74 , C07D249/12 , C07D271/07 , C07D401/06 , C07D401/12 , C07D403/06 , C07D403/12 , C07D417/06 , C07D491/10
摘要： Hydroxamic acid derivatives of the formula ##STR1## and pharmaceutically acceptable salts thereof, which are collagenase inhibitors useful for the control or prevention of degenerative joint diseases, such as, rheumatoid arthritis and osteoarthritis or for the treatment of invasive tumors, atherosclerosis or multiple sclerosis, are described. Said compounds can be prepared either by hydroxamidating a corresponding carboxylic acid or deprotecting a corresponding benzyloxycarbamoyl compound.
摘要翻译：式（I）的羟氨肟酸衍生物及其药学上可接受的盐，其是可用于控制或预防退行性关节疾病例如类风湿性关节炎和骨关节炎或用于治疗侵袭性肿瘤的胶原酶抑制剂，动脉粥样硬化或多发性硬化症。所述化合物可以通过将相应的羧酸异羟肟化或相应的苄氧基氨基甲酰基化合物脱保护来制备。

3. 发明授权

US5304549A Amino acid derivatives 失效
标题翻译：氨基酸衍生物
公开(公告)号：US5304549A
公开(公告)日：1994-04-19
申请号：US823212
申请日：1992-01-21
申请人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
发明人： Michael J. Broadhurst , Paul A. Brown , William H. Johnson , Geoffrey Lawton
IPC分类号： A61K31/66 , A01N37/18 , A01N57/16 , A61K20060101 , A61K31/135 , A61P9/10 , A61P29/00 , C07C20060101 , C07C235/12 , C07C237/22 , C07C259/06 , C07C279/36 , C07C281/16 , C07D207/40 , C07D207/404 , C07D209/48 , C07D295/13 , C07D295/15 , C07F9/28 , C07F9/30 , C07F9/38 , C07F9/40 , C07F9/48 , C07F9/553 , C07F9/576 , C07F9/62 , C07F9/6558 , A61K31/16 , A61K31/185 , A61K31/675 , C07C259/04 , C07F9/06 , C07C93/10
CPC分类号： C07D207/404 , C07C237/22 , C07C259/06 , C07C279/36 , C07D209/48 , C07D295/13 , C07D295/15 , C07F9/301 , C07F9/4816 , C07F9/5537 , C07F9/5765 , C07F9/65583 , Y10S514/825
摘要： Compounds of the formula ##STR1## wherein A is the group ##STR2## R.sup.1 is hydrogen, amino, protected amino, acylamino or lower alkyl optionally substituted by aryl, hydroxy, protected hydroxy, amino, protected amino, acylamino, maleimido, succinimido, naphthalimido, 2,3-dihydro-1,3-dioxo-1H-benz[d,e]isoquinol-2-yl, carboxy, protected carboxy, carbamoyl, mono(lower alkyl)carbamoyl, di(lower alkyl)carbamoyl, di(lower alkyl)amino, carboxy-lower alkanoylamino, pyrrolidino or morpholino; R.sup.2 is hydrogen or lower alkyl optionally substituted by aryl, amino, protected amino, di(lower alkyl)- amino, guanidino, carboxyl, protected carboxyl, carbamoyl, mono(lower alkyl) carbamoyl, di(lower alkyl)carbamoyl, di(lower alkoxy)phosphinyl, dihydroxyphosphinyl, pyrrolidino, piperidino or morpholino; R.sup.3 is hydrogen or lower alkyl optionally substituted by hydroxy, protected hydroxy, amino or protected amino; R.sup.4 is hydrogen, hydroxy, lower alkoxy or benzyloxy; and R.sup.5 is hydrogen or halogen and their pharmaceutically acceptable salts, which are useful for the control or prevention of degenerative joint diseases or for the treatment of invasive tumors, atherosclerosis or multiple sclerosis are described.
摘要翻译：（*化学结构*）（I）的化合物其中A是基团（*化学结构*）（a）（*化学结构*）（b）R 1是氢，氨基，被保护的氨基，酰氨基或低级烷基，被芳基，羟基，被保护的羟基，氨基，被保护的氨基，酰氨基，马来酰亚胺基，琥珀酰亚胺基，萘酰亚胺基，2,3-二氢-1,3-二氧代-1H-苯并（d，e）异喹啉-2-基，羧基，保护的羧基，氨基甲酰基，单（低级烷基）氨基甲酰基，二（低级烷基）氨基甲酰基，二（低级烷基）氨基，羧基 - 低级烷酰基氨基，吡咯烷子基或吗啉代; 氨基，氨基，胍基，羧基，被保护的羧基，氨基甲酰基，单（低级烷基）氨基甲酰基，二（低级烷基）氨基甲酰基，二（低级）烷氧基）氧膦基，二羟基氧膦基，吡咯烷子基，哌啶子基或吗啉代; R3是氢或任选被羟基，保护的羟基，氨基或被保护的氨基取代的低级烷基; R4是氢，羟基，低级烷氧基或苄氧基; 和R5是氢或卤素及其可用于控制或预防退行性关节疾病或用于治疗侵袭性肿瘤，动脉粥样硬化或多发性硬化的药学上可接受的盐。

4. 发明授权

US5006651A Phosphinic acid derivatives 失效
公开(公告)号：US5006651A
公开(公告)日：1991-04-09
申请号：US410779
申请日：1989-09-22
申请人： Michael J. Broadhurst , Balraj K. Handa , William H. Johnson , Geoffrey Lawton , Peter J. Machin
发明人： Michael J. Broadhurst , Balraj K. Handa , William H. Johnson , Geoffrey Lawton , Peter J. Machin
IPC分类号： A61K38/00 , C07K5/06
CPC分类号： C07K5/06191 , A61K38/00
摘要： The invention relates compounds of the formula ##STR1## wherein R.sup.1 -R.sup.5 and X have the significance given in the description, and their pharmaceutically acceptable salts. The compounds of formula I inhibit the enzyme collagenase and can be used in the form of medicaments for the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis.

5. 发明授权

US4885283A Phosphinic acid derivatives 失效
标题翻译：次膦酸衍生物
公开(公告)号：US4885283A
公开(公告)日：1989-12-05
申请号：US126643
申请日：1987-12-01
申请人： Michael J. Broadhurst , Balraj K. Handa , William H. Johnson , Geoffrey Lawton , Peter J. Machin
发明人： Michael J. Broadhurst , Balraj K. Handa , William H. Johnson , Geoffrey Lawton , Peter J. Machin
IPC分类号： A61K38/00 , C07K5/06
CPC分类号： C07K5/06191 , A61K38/00
摘要： The invention relates compounds of the formula ##STR1## wherein R.sup.1 -R.sup.5 and X have the significance given in the description, and their pharmaceutically acceptable salts. The compounds of formula I inhibit the enzyme collagenase and can be used in the form of medicaments for the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis.

6. 发明授权

US4762924A Bicyclic compounds 失效
标题翻译：双环化合物
公开(公告)号：US4762924A
公开(公告)日：1988-08-09
申请号：US62033
申请日：1987-06-15
申请人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
发明人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
IPC分类号： C07D237/04 , C07D487/04 , C07D245/00 , A61K31/50 , C07D487/06
CPC分类号： C07D487/04 , C07D237/04
摘要： Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, alkanoyl or aroyl; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen or aryl; R.sup.4 and R.sup.5 each are hydrogen or R.sup.4 and R.sup.5 taken together are oxo; and Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 -- or --N(R.sup.6)-- in which R.sup.6 is hydrogen, alkyl or aralkyl,as well as pharmaceutically acceptable salts thereof with bases when R.sup.2 is hydrogen and pharmaceutically acceptable salts thereof with acids when Y is --N(R.sup.6)--, which have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations, are described.The compounds of formula I contain at least one asymmetric carbon atom. Therefore, the invention comprises not only the optically uniform forms of these compounds, but also the various diastereoisomeric racemates and mixtures of different diastereoisomeric racemates.
摘要翻译：式Ⅰ的化合物，其中R1是氢，烷酰基或芳酰基; R2是氢或烷基; R3是氢或芳基; R4和R5各自为氢或R4和R5一起为氧代; 其中当R 2为氢时，其中R 6为氢，烷基或芳烷基，以及其与碱的药学上可接受的盐及其与Y的药学上可接受的盐，Y为-CH 2 - ， - CH 2 CH 2 - 或-N（R 6）描述了具有抗高血压活性并且可以用作药物制剂形式的药物的-N（R 6） - 。式I化合物含有至少一个不对称碳原子。因此，本发明不仅包括这些化合物的光学均匀形式，还包括各种非对映异构体外消旋体和不同非对映异构体外消旋体的混合物。

7. 发明授权

US4658024A Pyrazolo [1,2-a][1,2]-diazepines useful as antihypertensives 失效
标题翻译：吡唑并[1,2-a] [1,2] - 二氮杂作为抗高血压药物
公开(公告)号：US4658024A
公开(公告)日：1987-04-14
申请号：US697559
申请日：1985-02-01
申请人： Michael R. Attwood , Cedric H. Hassall , Robert W. Lambert , Geoffrey Lawton , Sally Redshaw
发明人： Michael R. Attwood , Cedric H. Hassall , Robert W. Lambert , Geoffrey Lawton , Sally Redshaw
IPC分类号： C07D209/48 , C07D231/04 , C07D237/04 , C07D403/06 , C07D487/04 , C07F9/38 , C07F9/40 , C07F9/6509 , C07F9/6561 , C07K5/078 , C07D403/04 , A61K31/33 , C07D401/04
CPC分类号： C07D209/48 , C07D231/04 , C07D237/04 , C07D403/06 , C07D487/04 , C07F9/3886 , C07F9/409 , C07F9/650947 , C07F9/6561 , C07K5/06139
摘要： Novel compounds of the formula ##STR1## wherein B represents a methylene, ethylene or vinylene group, R.sup.1 represents a hydrogen atom or an alkyl, aralkyl, amino-alkyl, mono-alkylamino-alkyl, dialkylamino-alkyl, acylamino-alkyl, phthalimido-alkyl, alkoxycarbonylamino-alkyl, aryloxycarbonylamino-alkyl, aralkoxycarbonylamino-alkyl, alkylaminocarbonylamino-alkyl, arylaminocarbonylamino-alkyl, aralkylaminocarbonylamino-alkyl, alkylsulphonylamino-alkyl or arylsulphonylamino-alkyl group, R.sup.2 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group or a group of the formula ##STR2## R.sup.3 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group, R.sup.4 and R.sup.5 each represent a hydrogen atom or R.sup.4 and R.sup.5 together represent an oxo group, R.sup.6 and R.sup.7 each represent a hydrogen atom or an alkyl or aralkyl group or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heteromonocyclic ring which may contain a further nitrogen atom or an oxygen or sulphur atom, and n stands for zero, 1 or 2, and pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations.
摘要翻译：新颖的式Ⅰ化合物，其中B代表亚甲基，亚乙基或亚乙烯基，R 1表示氢原子或烷基，芳烷基，氨基 - 烷基，单烷基氨基 - 烷基，二烷基氨基 - 烷基，酰氨基 - 烷基，邻苯二甲酰亚氨基烷基，烷氧基羰基氨基 - 烷基，烷基氨基羰基氨基 - 烷基，芳基氨基羰基氨基 - 烷基，芳烷基氨基羰基氨基 - 烷基，烷基磺酰基氨基 - 烷基或芳基磺酰基氨基 - 烷基，式中，R 3表示羧基，烷氧基羰基或芳烷氧基羰基，R 4和R 5各自表示氢原子或R 4，R 5一起表示氧代基，R 6和R 7各自表示氢原子或烷基或芳烷基，或者R 6和R 7 与它们所连接的氮原子一起表示可以含有另外的氮原子或氧的5元或6元杂单环，或硫原子，n表示0,1或2，其药学上可接受的盐具有抗高血压活性，可用作药物制剂形式的药物。

8. 发明授权

US4826980A Pyridazine intermediates 失效
标题翻译：哒嗪中间体
公开(公告)号：US4826980A
公开(公告)日：1989-05-02
申请号：US217805
申请日：1988-07-12
申请人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
发明人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
IPC分类号： C07D237/04 , C07D487/04 , C07D237/24 , C07D237/18
CPC分类号： C07D487/04 , C07D237/04
摘要： Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, alkanoyl or aroyl; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen or aryl; R.sup.4 and R.sup.5 each are hydrogen or R.sup.4 and R.sup.5 taken together are oxo; and Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 -- or --N(R.sup.6)-- in which R.sup.6 is hydrogen, alkyl or aralkyl, as well as pharmaceutically acceptable salts thereof with bases when R.sup.2 is hydrogen and pharmaceutically acceptable salts thereof with acids when Y is --N(R.sup.6)--, which have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations, are described.The compounds of formula I contain at least one asymmetric carbon atom. Therefore, the invention comprises not only the optically uniform forms of these compounds, but also the various diastereoisomeric racemates and mixtures of different diastereoisomeric racemates.
摘要翻译：式Ⅰ的化合物，其中R1是氢，烷酰基或芳酰基; R2是氢或烷基; R3是氢或芳基; R4和R5各自为氢或R4和R5一起为氧代; 其中当R 2为氢时，其中R 6为氢，烷基或芳烷基，以及其与碱的药学上可接受的盐及其与Y的药学上可接受的盐，Y为-CH 2 - ， - CH 2 CH 2 - 或-N（R 6）描述了具有抗高血压活性并且可以用作药物制剂形式的药物的-N（R 6） - 。式I化合物含有至少一个不对称碳原子。因此，本发明不仅包括这些化合物的光学均匀形式，还包括各种非对映异构体外消旋体和不同非对映异构体外消旋体的混合物。

9. 发明授权

US4743687A Pyridazo (1,2-a) (1,2) diazepine derivatives 失效
标题翻译：哒唑（1,2-a）（1,2）二氮杂衍生物
公开(公告)号：US4743687A
公开(公告)日：1988-05-10
申请号：US877085
申请日：1986-06-23
申请人： Geoffrey Lawton , Sally Redshaw
发明人： Geoffrey Lawton , Sally Redshaw
IPC分类号： C07D487/04 , C07F20060101 , C07F9/645 , C07F9/6561 , A61K31/50 , A61K31/55 , C07D237/04
CPC分类号： C07D487/04 , C07F9/645 , C07F9/6561
摘要： Compounds of the formula ##STR1## wherein R.sup.1 represents hydroxy, alkyl, aralkyl, aralkoxy-alkyl, hydroxy-alkyl, amino-alkyl, acylamino-alkyl, monoalkylamino-alkyl, dialkylamino-alkyl, alkoxycarbonylamino-alkyl, halo-alkyl, carboxy-alkyl, alkoxycarbonyl-alkyl, alkoxy or aralkoxy; R.sup.2 and R.sup.3 each represent hydrogen, alkyl or aralkyl; R.sup.4 and R.sup.5 each represent hydrogen or R.sup.4 and R.sup.5 together represent oxo; and X represents an oxygen atom or the group --NR.sup.6 -- in which R.sup.6 represents hydrogen, alkyl or aralkyl or --(CH.sub.2).sub.n -- in which n stands for zero, 1 or 2,and racemates, enantiomers, diastereoisomers or pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations. They can be prepared according to known methods.Compounds useful as starting materials for producing the compounds of formula I are also provided.
摘要翻译：式I的化合物，其中R 1表示羟基，烷基，芳烷基，芳烷氧基 - 烷基，羟基 - 烷基，氨基 - 烷基，酰氨基 - 烷基，单烷基氨基 - 烷基，二烷基氨基 - 烷基，烷氧基羰基氨基 - 烷基，卤代烷基，羧基烷基，烷氧基羰基 - 烷基，烷氧基或芳烷氧基; R2和R3各自表示氢，烷基或芳烷基; R4和R5各自表示氢或R4和R5一起代表氧代; 并且X表示氧原子或基团-NR 6 - ，其中R 6表示氢，烷基或芳烷基或 - （CH 2）n - ，其中n代表0,1或2，以及外消旋物，对映异构体，非对映异构体或其药学上可接受的盐具有抗高血压活性，可用作药物制剂形式的药物。它们可以根据已知方法制备。还提供了可用作制备式I化合物的起始原料的化合物。

10. 发明授权

US4785093A Bicyclic compounds 失效
标题翻译：双环化合物
公开(公告)号：US4785093A
公开(公告)日：1988-11-15
申请号：US48172
申请日：1987-05-11
申请人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
发明人： Cedric H. Hassall , Geoffrey Lawton , Sally Redshaw
IPC分类号： C07D237/04 , C07D487/04 , C07D245/00 , A61K31/50 , C07D487/06
CPC分类号： C07D487/04 , C07D237/04
摘要： Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, alkanoyl or aroyl; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen or aryl; R.sup.4 and R.sup.5 each are hydrogen or R.sup.4 and R.sup.5 taken together are oxo; and Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --or--N(R.sup.6)--in which R.sup.6 is hydrogen, alkyl or aralkyl, as well as pharmaceutically acceptable salts thereof with bases when R.sup.2 is hydrogen and pharmaceutically acceptable salts thereof with acids when Y is --N(R.sup.6)--, which have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations, are described.The compounds of formula I contain at least one asymmetric carbon atom. Therefore, the invention comprises not only the optically uniform forms of these compounds, but also the various diastereoisomeric racemates and mixtures of different diastereoisomeric racemates.
摘要翻译：式Ⅰ的化合物，其中R1是氢，烷酰基或芳酰基; R2是氢或烷基; R3是氢或芳基; R4和R5各自为氢或R4和R5一起为氧代; 并且Y是-CH 2 - ， - CH 2 CH 2 - 或-N（R 6） - 当R 2是氢时，R 6是氢，烷基或芳烷基，以及其与碱的药学上可接受的盐，当Y是描述了具有抗高血压活性并且可以用作药物制剂形式的药物的-N（R 6） - 。式I化合物含有至少一个不对称碳原子。因此，本发明不仅包括这些化合物的光学均匀形式，还包括各种非对映异构体外消旋体和不同非对映异构体外消旋体的混合物。

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