Bu4NI-Catalyzed Oxygen-Centered Radical Addition between Acyl Peroxides and Isocyanides
A novel oxygen-centered radical addition between acyl peroxides and isocyanides has been developed. A diverse collection of valuable arylcarboxyamides were easily synthesized by this protocol. From the preliminary mechanistic study, the elimination of carbon dioxide affords the product via an intramolecular rearrangement.
Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors
A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3- (ethylamino)-2-pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Replacement of the substituted aryl moiety with various substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Extensive preclinical evaluations of several of these compounds led to the selection of 1-[(5-methoxyindol-2-yl)carbonyl]-4-[3-(ethylamino)-2- pyridyl]piperazine methanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.