The recent discovery of GSK3532795 (formerly BMS-955176) as a second-generation HIV-1 maturation inhibitor has shown broad spectrum antiviral activity and preclinical PK predictive of once daily dosing can be achieved.  To further evaluate the chemotype for additional potency, we explored benzoic acid surrogates designed to probe the perceived binding pocket.  While evaluating more traditional benzene bioisosteres, a spiro[3.3]hept-5-ene was shown to closely emulate the benzene moiety from both a potency and PK perspective.  Unlike other traditional benzene replacements such as pyridine and acetylene, spiro[3.3]hept-5-ene allows for a modification of a second vector which could be helpful to probe SAR.  To our knowledge, this is the first reporting of a spiro[3.3]hept-5-ene as a benzene replacement.<br/>

Spiro[3.3]hept-5-ene-2-carboxylic acid as a benzoic acid bioisostere: Design and application of a novel benzoic acid replacement as an HIV-1 maturation inhibitor

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.