新型二苯甲酮类化合物作为HIV-1的非核苷类逆转录酶抑制剂

Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1.

作者信息

Chan Joseph H, Freeman George A, Tidwell Jeffrey H, Romines Karen R, Schaller Lee T, Cowan Jill R, Gonzales Steve S, Lowell Gina S, Andrews C W, Reynolds David J, St Clair Marty, Hazen Richard J, Ferris Rob G, Creech Katrina L, Roberts Grace B, Short Steven A, Weaver Kurt, Koszalka George W, Boone Lawrence R

机构信息

GlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA.

出版信息

J Med Chem. 2004 Feb 26;47(5):1175-82. doi: 10.1021/jm030255y.

DOI:10.1021/jm030255y

PMID:14971897

Abstract

GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1 and <10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.

摘要

GW4511、GW4751和GW3011对野生型HIV-1的IC50值≤2 nM，对16种突变体的IC50值<10 nM。它们对含有Y181C、K103N以及基于K103N的双突变的非核苷类逆转录酶抑制剂（NNRTI）耐药病毒特别有效，而这些突变在目前上市的三种NNRTI临床治疗失败病例中占很大比例。抗病毒数据以及GW4511良好的药代动力学数据表明，这些二苯甲酮具有新型NNRTI候选药物的特性。