超强效P1修饰的芳基磺酰胺类HIV蛋白酶抑制剂：GW0385的发现。
Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.
作者信息
Miller John F, Andrews C Webster, Brieger Michael, Furfine Eric S, Hale Michael R, Hanlon Mary H, Hazen Richard J, Kaldor Istvan, McLean Ed W, Reynolds David, Sammond Douglas M, Spaltenstein Andrew, Tung Roger, Turner Elizabeth M, Xu Robert X, Sherrill Ronald G
机构信息
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
出版信息
Bioorg Med Chem Lett. 2006 Apr 1;16(7):1788-94. doi: 10.1016/j.bmcl.2006.01.035. Epub 2006 Feb 3.
A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.
合成了一系列新型的P1修饰的HIV蛋白酶抑制剂，并对其针对野生型病毒和蛋白酶抑制剂耐药病毒的体外抗病毒活性进行了评估。对P1部分的优化产生了具有飞摩尔酶活性和低纳摩尔范围内细胞抗病毒活性的化合物，最终确定了临床候选药物GW0385。
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