Flosi, William J. published the artcileDiscovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV, Category: pyrimidines, the main research area is imidazolidinedione lopinavir analog preparation HIV protease inhibitor SAR.
A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity vs. wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in MT-4 cells). Select imidazolidine-2,4-dione containing PIs were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 μg h/mL.
Bioorganic & Medicinal Chemistry published new progress about AIDS (disease). 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, Category: pyrimidines.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia