Benzophenone Derivatives: A Novel Series of Potent and Selective Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Article abstract of DOI:10.1021/jm00010a010

A series of benzophenone derivatives has been synthesized and evaluated 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 relationships within this series of compounds and computational chemistry techniques, a binding conformation is proposed.The SAR also indicated that the major interactions of 1h with the RT enzyme are through hydrogen bonding of the amide and benzophenone carbonyls and ?-orbital interactions with the benzophenone nucleus and an aromatic function separated from the benzophenone by a suitable spacer group.The crystal structure of compound 1h has been determined.A number of compounds with potent inhibitory activity against HIV-1 RT and HIV in cellular assays at levels comparable with AZT and our efforts to identify a metabolically stable analogue are described.