Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of (+/-)-benzhydrol derivatives featuring the essential sulfonamide group at the para position on the C-ring were synthesized and evaluated for the potential anti-HIV activity in C8166 cells. Most of these analogues demonstrated low concentration inhibitory activity with EC50 values less than 1 mu M against the wild-type HIV-1. In particular, compound 7h was identified as the highest active inhibitor of wildtype HIV-1 with an EC50 value of 0.12 mu M and selectivity index value of 312.73. Furthermore, some of them also exhibited moderate activity against the double mutant strain A(17) (K103N + Y181C) with EC50 values lower than 5 mu M. In addition, the binding modes with RT and the preliminary structure-activity relationships of these derivatives were also explored for further chemical modifications. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.