Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine

J Med Chem. 1992 Aug 7;35(16):2958-69. doi: 10.1021/jm00094a005.

K L Yu ¹, J J Bronson, H Yang, A Patick, M Alam, V Brankovan, R Datema, M J Hitchcock, J C Martin

Affiliations

Affiliation

1 Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660.

PMID: 1323678 DOI: 10.1021/jm00094a005

Abstract

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)-3] and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6 microM, 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.

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