申请人:Bristol-Myers Company
公开号:EP0629604A2
公开(公告)日:1994-12-21
Compounds of Formula I:
wherein the bonds between C₂ and C3 and/or between C₄ and C₅ are unsaturated;
X = COOH, H, F, Cl, Br, I, COOR'', CONH₂, COR''', CHO, CH₂OH, CH₂OR''', OH, OR''', CF₃, C1-6 alkyl, C1-6 alkenyl, C1-6 haloalkyl, NO₂, P(O)(OH)₂, SO₂H, or SO₃H;
R = substituted or unsubstituted alkyl, aryl, arylalkyl, alkenyl, or arylalkenyl groups, with the proviso that each of these groups must have 6 or more carbons (preferably 6 to 30) and R cannot be
R' = H or C1-6 alkyl;
R'' = H, C1-6 alkyl, C(R³)₂OC(O)R⁴, CH₂CH₂NR⁵R⁶, CH₂CH₂CH₂NR⁵R⁶, CH₂C(O)N(R⁶)₂, or other groups yielding physiologically hydrolyzable esters;
R''' = C1-6 alkyl;
R³ = H, CH₃, C₂H₅, CH₃CH₂CH₂ (with R³'s being the same or different);
R⁴ = C6-12 aryl, C1-7 linear, branched or cyclic alkyl, or C1-7 linear, branched or cyclic alkoxy;
R⁵ = R⁶, or when linked with R⁶, is a C₃-C₆ cycloalkyl or a -CH₂CH₂OCH₂CH₂-group; and
R⁶ = C1-3 alkyl;
and pharmaceutically-acceptable salts thereof are effective phospholipase A₂ (PLA₂) inhibitors.
式 I 的化合物:
其中 C₂ 与 C3 之间和/或 C₄ 与 C₅ 之间的键为不饱和键;
X = COOH、H、F、Cl、Br、I、COOR''、CONH₂、COR'''、CHO、CH₂OH、CH₂OR'''、OH、OR'''、CF₃、C1-6 烷基、C1-6 烯基、C1-6 卤代烷基、NO₂、P(O)(OH)₂、SO₂H 或 SO₃H;
R = 取代或未取代的烷基、芳基、芳烷基、烯基或芳烷烯基,但这些基团都必须具有 6 个或更多的碳原子(最好是 6 至 30 个),且 R 不能是
R' = H 或 C1-6 烷基;
R''=H、C1-6 烷基、C(R³)₂OC(O)R⁴、CH₂CH₂NR⁵R⁶、CH₂CH₂CH₂NR⁵R⁶、CH₂C(O)N(R⁶)₂ 或其他可产生生理性水解酯的基团;
R''' = C1-6 烷基;
R³ = H、CH₃、C₂H₅、CH₃CH₂CH₂(R³'s 相同或不同);
R⁴ = C6-12 芳基,C1-7 直链、支链或环状烷基,或 C1-7 直链、支链或环状烷氧基;
R⁵ = R⁶,或当与 R⁶ 连接时,为 C₃-C₆ 环烷基或-CH₂CH₂OCH₂CH₂基团;以及
R⁶ = C1-3 烷基;
及其药学上可接受的盐是有效的磷脂酶 A₂(PLA₂)抑制剂。