HIV-1 Vif-载脂蛋白B编辑酶催化多肽样蛋白3G轴抑制剂的构效关系及先导化合物优化
SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor.
作者信息
Mohammed Idrees, Parai Maloy K, Jiang Xinpeng, Sharova Natalia, Singh Gatikrushna, Stevenson Mario, Rana Tariq M
机构信息
Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
Division of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, FL 33136 (USA).
出版信息
ACS Med Chem Lett. 2012 Jun 14;3(6):465-469. doi: 10.1021/ml300037k.
Abstract
We describe structure-activity 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-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar ( and ) and improved (, , and ) activities. Two potent water-soluble RN-18 analogues, and are also disclosed, and we describe the results of pharmacological studies with compound 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.
摘要
我们描述了HIV-1 Vif-APOBEC3G轴抑制剂RN-18的构效关系及优化研究。对RN-18的C环、B环、A环、A-B桥和B-C桥进行了靶向修饰，以确定关键结构特征，从而产生了具有相似（ 和 ）及改进（ 、 和 ）活性的新抑制剂。还公开了两种有效的水溶性RN-18类似物 和 ，并且我们描述了化合物 的药理学研究结果。此处所述的研究结果将有助于开发更有效的Vif抑制剂以及设计用于鉴定RN-18及其类似物靶蛋白的探针。
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