title: SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor.
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 (4gand4i) and improved (5,8b, and11) activities. Two potent water-soluble RN-18 analogues,17and19,are also disclosed, and we describe the results of pharmacological studies with compound19.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.
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
authors.forename: Idrees
authors.initials: I
authors.lastname: Mohammed
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
authors.forename: Maloy K
authors.initials: MK
authors.lastname: Parai
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Division of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, FL 33136 (USA).
authors.forename: Natalia
authors.initials: N
authors.lastname: Sharova
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
authors.forename: Gatikrushna
authors.initials: G
authors.lastname: Singh
authors.affiliation: Division of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, FL 33136 (USA).
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
keywords: HIV-1 Vif-APOBEC3G axis inhibition; RN-18; pharmacological studies; structure-activity relationship and optimization