doi: 10.1021/jm9800806.
Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV
Affiliations
- PMID: 9748354
- DOI: 10.1021/jm9800806
Item in Clipboard
Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV
J Med Chem.
.
Abstract
A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1IIIB-WT and retain good activity against a laboratory-derived HIV-1MF delavirdine-resistant variant.
Similar articles
-
Difluoromethylbenzoxazole pyrimidine thioether derivatives: a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors.J Med Chem. 2011 Dec 8;54(23):7974-85. doi: 10.1021/jm200766b. Epub 2011 Nov 4. J Med Chem. 2011. PMID: 22017513
-
Dihydro-alkylthio-benzyl-oxopyrimidines as inhibitors of reverse transcriptase: synthesis and rationalization of the biological data on both wild-type enzyme and relevant clinical mutants.J Med Chem. 2007 Dec 27;50(26):6580-95. doi: 10.1021/jm0708230. Epub 2007 Dec 6. J Med Chem. 2007. PMID: 18052319
-
Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants.Virology. 2001 Jul 5;285(2):193-203. doi: 10.1006/viro.2001.0920. Virology. 2001. PMID: 11437654
-
Recent advances in the DABOs family as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.Curr Med Chem. 2011;18(16):2376-85. doi: 10.2174/092986711795843209. Curr Med Chem. 2011. PMID: 21568919 Review.
-
Progress of bis(heteroaryl)piperazines (BHAPs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) against human immunodeficiency virus type 1 (HIV-1).Mini Rev Med Chem. 2010 Jan;10(1):62-72. doi: 10.2174/138955710791112578. Mini Rev Med Chem. 2010. PMID: 20380641 Review.
Cited by
-
Targeting HIV/HCV Coinfection Using a Machine Learning-Based Multiple Quantitative Structure-Activity Relationships (Multiple QSAR) Method.Int J Mol Sci. 2019 Jul 22;20(14):3572. doi: 10.3390/ijms20143572. Int J Mol Sci. 2019. PMID: 31336592 Free PMC article.
-
C2-Selective Palladium-Catalyzed C-S Cross-Coupling of 2,4-Dihalopyrimidines.J Am Chem Soc. 2025 Jan 29;147(4):3017-3022. doi: 10.1021/jacs.4c17020. Epub 2025 Jan 19. J Am Chem Soc. 2025. PMID: 39829005
-
Discovery of novel inhibitors of HIV-1 reverse transcriptase through virtual screening of experimental and theoretical ensembles.Chem Biol Drug Des. 2014 May;83(5):521-31. doi: 10.1111/cbdd.12277. Epub 2014 Mar 24. Chem Biol Drug Des. 2014. PMID: 24405985 Free PMC article.
-
An Amazing 30-Year Journey around the DABO Family: A Medicinal Chemistry Lesson on a Versatile Class of Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors.J Med Chem. 2025 Mar 27;68(6):5993-6026. doi: 10.1021/acs.jmedchem.4c02848. Epub 2025 Mar 7. J Med Chem. 2025. PMID: 40053382 Free PMC article. Review.
-
An efficient three-component, one-pot synthesis of 2-alkylthio-4-amino-5-cyano-6-aryl(alkyl)pyrimidines in water.Mol Divers. 2012 Aug;16(3):431-9. doi: 10.1007/s11030-012-9376-z. Epub 2012 Jun 28. Mol Divers. 2012. PMID: 22740103 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information
Medical
