Difluoromethylbenzoxazole Pyrimidine Thioether Derivatives: A Novel Class of Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors
Författare
Summary, in English
This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron transfer chain process (radical nucleophilic substitution, Si) and were found to be potent against wild-type HIV-1 reverse transcriptase, with low cytotoxicity but with moderate activity against drug-resistant strains. The most promising compound 2,4 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 mu M against an NNRTI resistant double mutant (K103N + Y181C), but an excellent selectivity index >15477 (CC(50) > 100 mu M).
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
7974-7985
Publikation/Tidskrift/Serie
Journal of Medicinal Chemistry
Volym
54
Issue
23
Dokumenttyp
Artikel i tidskrift
Förlag
The American Chemical Society (ACS)
Ämne
- Medicinal Chemistry
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1520-4804