Janusz J M, Young P A, Ridgeway J M, Scherz M W, Enzweiler K, Wu L I, Gan L, Chen J, Kellstein D E, Green S A, Tulich J L, Rosario-Jansen T, Magrisso I J, Wehmeyer K R, Kuhlenbeck D L, Eichhold T H, Dobson R L
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA.
J Med Chem. 1998 Aug 27;41(18):3515-29. doi: 10.1021/jm9802416.
We report an expansion of the scope of our initial discovery that 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.
我们报告了最初发现的范围扩展，即5-酮基取代的7-叔丁基-2,3-二氢-3,3-二甲基苯并呋喃（DHDMBFs）是抗炎和镇痛剂。在5位引入了其他几个官能团：5位的酰胺、脒、脲、胍、胺、杂环、杂芳族化合物和杂芳基乙烯基取代基均提供活性化合物。这些化合物是双重环氧化酶（COX）和5-脂氧合酶（5-LOX）抑制剂。它们对COX-1和COX-2均有抑制作用，对COX-2的选择性高达33倍。
