doi: 10.1021/jm00099a007.
Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one
Affiliations
- PMID: 1279173
- DOI: 10.1021/jm00099a007
Item in Clipboard
Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one
J Med Chem.
.
Abstract
A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methy lpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.
Similar articles
-
Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogues.J Med Chem. 1993 Apr 16;36(8):953-66. doi: 10.1021/jm00060a002. J Med Chem. 1993. PMID: 7683054
-
Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.J Med Chem. 1993 Jan 22;36(2):249-55. doi: 10.1021/jm00054a009. J Med Chem. 1993. PMID: 7678654
-
Pyridinone derivatives: specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity.Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6863-7. doi: 10.1073/pnas.88.15.6863. Proc Natl Acad Sci U S A. 1991. PMID: 1713693 Free PMC article.
-
The genetic and functional basis of HIV-1 resistance to nonnucleoside reverse transcriptase inhibitors.Arch Virol Suppl. 1994;9:11-7. doi: 10.1007/978-3-7091-9326-6_2. Arch Virol Suppl. 1994. PMID: 7518271 Review.
-
Clinical experience with non-nucleoside reverse transcriptase inhibitors: L-697,661 and nevirapine.Adv Exp Med Biol. 1996;394:291-8. doi: 10.1007/978-1-4757-9209-6_26. Adv Exp Med Biol. 1996. PMID: 8815693 Review. No abstract available.
Cited by
-
A review on synthetic chalcone derivatives as tubulin polymerisation inhibitors.J Enzyme Inhib Med Chem. 2022 Dec;37(1):9-38. doi: 10.1080/14756366.2021.1976772. J Enzyme Inhib Med Chem. 2022. PMID: 34894980 Free PMC article. Review.
-
L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase.Antimicrob Agents Chemother. 1995 Dec;39(12):2602-5. doi: 10.1128/AAC.39.12.2602. Antimicrob Agents Chemother. 1995. PMID: 8592986 Free PMC article.
-
Quantitative structure-activity relationship analysis of pyridinone HIV-1 reverse transcriptase inhibitors using the k nearest neighbor method and QSAR-based database mining.J Comput Aided Mol Des. 2005 Apr;19(4):229-42. doi: 10.1007/s10822-005-4789-8. J Comput Aided Mol Des. 2005. PMID: 16163450
-
Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of Thiourea Derivatives Based on 3-Aminopyridin-2(1H)-Ones.Molecules. 2024 Jul 31;29(15):3627. doi: 10.3390/molecules29153627. Molecules. 2024. PMID: 39125032 Free PMC article.
-
Global 3D-QSAR methods: MS-WHIM and autocorrelation.J Comput Aided Mol Des. 2000 Mar;14(3):293-306. doi: 10.1023/a:1008142124682. J Comput Aided Mol Des. 2000. PMID: 10756483
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Chemical Information