公开(公告)号：EP1179529A1

公开(公告)日：2002-02-13

申请号：EP00927793.0

申请日：2000-05-17

申请人： Daiichi Fine Chemical Co., Ltd.

发明人： FUJISAWA, Tetsunori Daiichi Fine Chemical Co.,Ltd. ,  ODAKE, Shinjiro Daiichi Fine Chemical Co.,Ltd. ,  ITO, Hajime Daiichi Fine Chemical Co., Ltd. ,  YASUDA, Junko Daiichi Fine Chemical Co., Ltd. ,  OHTANI, Miwa Daiichi Fine Chemical Co., Ltd. ,  MORIKAWA, Tadanori Daiichi Fine Chemical Co., Ltd.

IPC分类号： C07C259/06 ,  C07C229/08 ,  C07C231/02 ,  C07C233/47 ,  A61K31/198 ,  A61K31/216 ,  A61P43/00

CPC分类号： C07C233/47 ,  C07C229/08 ,  C07C259/06 ,  C07C279/14 ,  Y02P20/55

摘要： Disclosed are compounds which have not only potent metalloproteinase-inhibiting activity but also amazingly excellent bioavailability and biological activity in vivo, including the property of being well absorbed via oral routes, thereby serving as useful pharmaceuticals, intermediates and processes for the production thereof. The disclosed compounds of the formula (I):
wherein R 1 is hydrogen, or a hydroxy-protecting group; R 2 is hydrogen, or an amino-protecting group; R 3 , R 7 , and R 8 , which may be identical or different, are each independently hydrogen, hydroxy, unsubstituted or optionally substituted (C 1 -C 6 ) alkyl, or unsubstituted or optionally substituted aryl-(C 1 -C 6 ) alkyl; R 4 is unsubstituted or optionally substituted (C 1 -C 6 ) alkyl, or unsubstituted or optionally substituted aryl-(C 1 -C 6 ) alkyl; R 5 is hydrogen, unsubstituted or optionally substituted alkyl, unsubstituted or optionally substituted aralkyl, or a carboxy-protecting group; R 6 is hydrogen, hydroxy, amino, and a group of the formula: -X-Y wherein X is oxygen, (C 1 -C 6 ) alkylene or phenylene, Y is a group of the formula: -A-B or -B, wherein A is (C 1 -C 6 ) alkylene, imino, and (C 1 -C 6 ) alkyleneimino, and B is hydrogen, amino, amidino, sulfonyl, acylimidoyl, unsubstituted or optionally substituted imidazolyl, unprotected or optionally protected bis(phosphono)methyl or unprotected or optionally protected bis(phosphono)hydroxymethyl; or salts thereof are useful for pharmaceutical and/or veterinary compositions, particularly as metalloproteinase inhibitors which inhibit matrix metalloproteinases or tumor necrosis factor-α-converting enzymes (TNF-α convertases).

摘要翻译： 公开了不仅具有有效的金属蛋白酶抑制活性，而且在体内具有惊人优异的生物利用度和生物活性的化合物，包括通过口服途径良好吸收的性质，从而作为有用的药物，中间体及其制备方法。 所公开的式（I）化合物：其中R 1是氢或羟基保护基的 R 2是氢或氨基保护基; R 3，R 7和R 8可以相同或不同，各自独立地为氢，羟基，未取代或任选取代的（C 1 -C 6）烷基，或未取代或任选取代的芳基 - （C 1 -C 6） -C 6）烷基; R 4是未取代的或任选取代的（C 1 -C 6）烷基，或未取代或任选取代的芳基 - （C 1 -C 6）烷基; R 5是氢，未取代或任选取代的烷基，未取代或任选取代的芳烷基或羧基保护基; R 6是氢，羟基，氨基和下式基团-XY，其中X是氧，（C1-C6）亚烷基或亚苯基，Y是下式的基团：-AB或-B，其中A 是（C 1 -C 6）亚烷基亚氨基，亚氨基和（C 1 -C 6）亚烷基亚氨基，B是氢，氨基，脒基，磺酰基，酰亚胺基，未取代的或任选取代的咪唑基，未被保护或任选被保护的双（膦酰基）甲基或未被保护或任选地 保护的双（膦酰基）羟甲基; 或其盐可用于药物和/或兽医组合物，特别是作为抑制基质金属蛋白酶或肿瘤坏死因子-α转化酶（TNF-α转化酶）的金属蛋白酶抑制剂。