Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular modeling studies

  • Bioorg Med Chem. 2013 Nov 1;21(21):6477-83. doi: 10.1016/j.bmc.2013.08.040.
Hai-Qiu Wu  1 ,  Zi-Hong Yan ,  Wen-Xue Chen ,  Qiu-Qin He ,  Fen-Er Chen ,  Erik De Clercq ,  Jan Balzarini ,  Dirk Daelemans ,  Christophe Pannecouque
Affiliations
  • 1. Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
PMID: 24055077 DOI: 10.1016/j.bmc.2013.08.040
Abstract

A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate Antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26μM and a selectivity index (SI) of 541. The preliminary structure-activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed.

Keywords
HIV-1 reverse transcriptase; NNRTIs; Rigid conformation; S-DABO; SAR.