SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor
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- 作者：Idrees Mohammed ; Maloy K. Parai ; Xinpeng Jiang ; Natalia Sharova ; Gatikrushna Singh ; Mario Stevenson ; Tariq M. Rana
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：June 14, 2012
- 年：2012
- 卷：3
- 期：6
- 页码：465-469
- 全文大小：342K
- 年卷期：v.3,no.6(June 14, 2012)
- ISSN：1948-5875
文摘
We describe structure鈥揳ctivity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring C, ring B, ring A, bridge A鈥揃, and bridge B鈥揅 were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.