Hagen, Susan E.; Domagala, John; Gajda, Christopher; Lovdahl, Michael; Tait, Bradley D.; Wise, Eric; Holler, Tod; Hupe, Donald; Nouhan, Carolyn; Urumov, Andrej; Zeikus, Greg; Zeikus, Eric; Lunney, Elizabeth A.; Pavlovsky, Alexander; Gracheck, Stephen J.; Saunders, James; VanderRoest, Steve; Brodfuehrer, Joanne published the artcile< 4-Hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: the effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters>, Category: thiazole, the main research area is hydroxydihydropyrone HIV protease inhibitor antiviral agent.
Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, the authors previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable back-up candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocycle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymic and cellular tests) and low cellular toxicity; furthermore, several analogs exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailability was (S)-3-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (I). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, I was chosen for further preclin. evaluation.
Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Category: thiazole.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica