doi: 10.1016/j.bmcl.2010.01.086.
Epub 2010 Jan 21.
N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase
Affiliations
- PMID: 20137928
- DOI: 10.1016/j.bmcl.2010.01.086
Item in Clipboard
N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase
Bioorg Med Chem Lett.
.
Abstract
A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. The co-crystal structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101 and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted in the discovery of compound 13, which represents the lead compound in this series with improved pharmacokinetics and similar potency as inhibitor 1.
Copyright 2010 Elsevier Ltd. All rights reserved.
Similar articles
-
N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.Bioorg Med Chem Lett. 2010 Mar 1;20(5):1589-92. doi: 10.1016/j.bmcl.2010.01.085. Epub 2010 Jan 21. Bioorg Med Chem Lett. 2010. PMID: 20138513
-
Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants.Bioorg Med Chem Lett. 2009 Sep 1;19(17):5119-23. doi: 10.1016/j.bmcl.2009.07.031. Epub 2009 Jul 10. Bioorg Med Chem Lett. 2009. PMID: 19631528
-
Design of annulated pyrazoles as inhibitors of HIV-1 reverse transcriptase.J Med Chem. 2008 Dec 11;51(23):7449-58. doi: 10.1021/jm800527x. J Med Chem. 2008. PMID: 19007201
-
Crystallography and the design of anti-AIDS drugs: conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors.Prog Biophys Mol Biol. 2005 Jun;88(2):209-31. doi: 10.1016/j.pbiomolbio.2004.07.001. Prog Biophys Mol Biol. 2005. PMID: 15572156 Review.
-
Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase.Virus Res. 2008 Jun;134(1-2):157-70. doi: 10.1016/j.virusres.2007.12.018. Epub 2008 Mar 3. Virus Res. 2008. PMID: 18313784 Review.
Cited by
-
1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents.Bioorg Med Chem. 2011 Oct 1;19(19):5794-802. doi: 10.1016/j.bmc.2011.08.025. Epub 2011 Aug 17. Bioorg Med Chem. 2011. PMID: 21903401 Free PMC article.
-
Identification of binding sites and favorable ligand binding moieties by virtual screening and self-organizing map analysis.BMC Bioinformatics. 2015 Mar 21;16:93. doi: 10.1186/s12859-015-0518-z. BMC Bioinformatics. 2015. PMID: 25888251 Free PMC article.
-
FluoroFusion: NHC-Catalyzed Nucleophilic Aromatic Substitution Reaction Unveils Functional Perfluorinated Diarylmethanones.Org Lett. 2024 Mar 22;26(11):2338-2342. doi: 10.1021/acs.orglett.4c00677. Epub 2024 Mar 8. Org Lett. 2024. PMID: 38458971 Free PMC article.
-
6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase.Bioorg Med Chem Lett. 2011 Apr 15;21(8):2400-2. doi: 10.1016/j.bmcl.2011.02.069. Epub 2011 Feb 18. Bioorg Med Chem Lett. 2011. PMID: 21392991 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
