Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance

• Published in: Chemical communications (Cambridge, England) Vol. 58; no. 84; pp. 11762 - 11782
• Main Authors: Ghosh, Arun K, Weber, Irene T, Mitsuya, Hiroaki
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 20.10.2022; Royal Society of Chemistry (RSC)
• Subjects: Chemical bonds; Crystallography, X-Ray; Darunavir - chemistry; Darunavir - pharmacology; Drug Design; Drug Resistance; Drug Resistance, Viral; Ether - pharmacology; Ethers; Heterocyclic compounds; HIV Protease - chemistry; HIV Protease - pharmacology; HIV Protease Inhibitors - pharmacology; HIV-1; Hydrogen bonding; Peptides - pharmacology; Protease; Protease inhibitors

We report our recent development of a conceptually new generation of exceptionally potent non-peptidic HIV-1 protease inhibitors that displayed excellent pharmacological and drug-resistance profiles. Our X-ray structural studies of darunavir and other designed inhibitors from our laboratories led us...