SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor

Idrees Mohammed; Maloy K. Parai; Xinpeng Jiang; Natalia Sharova; Gatikrushna Singh; Mario Stevenson; Tariq M. Rana

doi:10.1021/ml300037k

SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor

Idrees Mohammed, Maloy K. Parai, Xinpeng Jiang, Natalia Sharova, Gatikrushna Singh, Mario Stevenson, Tariq M. Rana

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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 (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.

Original language	English (US)
Pages (from-to)	465-469
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	6
DOIs	https://doi.org/10.1021/ml300037k
State	Published - May 14 2012
Externally published	Yes

Keywords

HIV-1 Vif-APOBEC3G axis inhibition
RN-18
pharmacological studies
structure-activity relationship and optimization

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AU - Mohammed, Idrees

AU - Parai, Maloy K.

AU - Jiang, Xinpeng

AU - Sharova, Natalia

AU - Singh, Gatikrushna

AU - Stevenson, Mario

AU - Rana, Tariq M.

PY - 2012/5/14

Y1 - 2012/5/14

N2 - 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 (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.

AB - 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 (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.

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SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor

Abstract

Keywords

UN SDGs

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