BENZOPHENONE DERIVATIVES - A NOVEL SERIES OF POTENT AND SELECTIVE INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE

A series of benzophenone derivatives has been synthesized and evaluate d as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells. Through the use of the structure-activity relatio nships within this series of compounds and computational chemistry tec hniques, a binding conformation is proposed. The SAR also indicated th at the major interactions of 1h with the RT enzyme are through hydroge n bonding of the amide and benzophenone carbonyls and pi-orbital inter actions with the benzophenone nucleus and an aromatic function separat ed from the benzophenone by a suitable spacer group. The crystal struc ture of compound 1h has been determined. A number of compounds with po tent inhibitory activity against HIV-1 RT and HIV in cellular assays a t levels comparable with AZT and our efforts to identify a metabolical ly stable analogue are described.