SYNTHESIS AND ANTIVIRAL ACTIVITY OF METHYL-DERIVATIVES OF 9-[2-(PHOSPHONOMETHOXY)ETHYL]GUANINE

被引：49

作者：

YU, KL

BRONSON, JJ

YANG, HK

PATICK, A

ALAM, M

BRANKOVAN, V

DATEMA, R

HITCHCOCK, MJM

MARTIN, JC

机构：

[1] Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Connecticut 06492-7660, 5 Research Parkway, Wallingford

[2] Gilead Sciences, Foster City, California

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 16期

关键词：

D O I：

10.1021/jm00094a005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti-human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'-methyl-PMEG [(R)-31 and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6-mu-M, respectively. The corresponding (S)-2'-methyl-PMEG [(S)-3] was found to be less potent against HIV. In addition, the (R) and (S) enantiomers of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine (HPMPG, 8) were prepared for comparison of biological activity, and shown to be active and equipotent against herpesviruses, but inactive against HIV.

引用

页码：2958 / 2969

页数：12

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