Synthesis and Biological Evaluation of C-5 Methyl Substituted 4-Arylthio and 4-Aryloxy-3-Iodopyridin-2(1H)-one Type Anti-HIV Agents

被引：23

作者：

Guillemont, Jerome ^{[1
]}

Benjahad, Abdellah ^{[2
]}

Oumouch, Said ^{[2
]}

Decrane, Laurence ^{[1
]}

Palandjian, Patrice ^{[1
]}

Vernier, Daniel ^{[1
]}

Queguiner, Laurence ^{[1
]}

Andries, Koen ^{[3
]}

de Bethune, Marie-Pierre ^{[4
]}

Hertogs, Kurt ^{[4
]}

Grierson, David S. ^{[2
]}

Nguyen, Chi Hung ^{[2
]}

机构：

[1] Dept Med Chem, TIBOTEC, F-27430 Val De Reuil, France

[2] Ctr Univ Orsay, CNRS, Inst Curie, UMR 176,Lab Pharmacochim,Sect Rech, F-91405 Orsay, France

[3] Johnson & Johnson Pharmaceut Res & Dev, Virol Drug Discovery, B-2340 Beerse, Belgium

[4] TIBOTEC, B-2800 Mechelen, Belgium

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 23期

关键词：

REVERSE-TRANSCRIPTASE INHIBITORS; IN-VITRO EVALUATION; PYRIDINONE DERIVATIVES; ANTIRETROVIRAL THERAPY; 1-<(2-HYDROXYETHOXY)METHYL>-6-(PHENYLTHIO)THYMINE HEPT; ANTIVIRAL ACTIVITY; MUTANT STRAINS; POTENT; ANALOGS; HETEROCYCLES;

D O I：

10.1021/jm900802y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of C-5 methyl substituted 4-arylthio- and 4-aryloxy-3-iodopyridin-2(1H)-ones hits been synthesized its new pyridinone analogues for their evaluation as anti-HIV inhibitors. The optimization at the 5-position wits developed through an efficient use of the key intermediates 5-ethoxycarbonyl- and 5-cyano-pyridin-2(1H)-ones (14 and 15). Biological studies revealed that several compounds show potent HIV-1 reverse transcriptase inhibitory properties, for example, compounds 93 and 99 are active at 0.6-50 nM against wild type HIV-1 and a panel of major simple/double HIV mutant strains.

引用

页码：7473 / 7487

页数：15

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