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一种膦酸酯前药的合成与体外评价：双（新戊酰氧甲基）9-（2-膦酰甲氧基乙基）腺嘌呤

Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine.

作者信息

Starrett J E, Tortolani D R, Hitchcock M J, Martin J C, Mansuri M M

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.

出版信息

Antiviral Res. 1992 Sep;19(3):267-73. doi: 10.1016/0166-3542(92)90084-i.

DOI:10.1016/0166-3542(92)90084-i
PMID:1332606
Abstract

9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold better than PMEA against HSV-1, and equipotent against HIV and HCMV. The toxicity of 2 was studied in both resting and growing cells.

摘要

9-(2-膦酰甲氧基乙基)腺嘌呤（PMEA；1）与新戊酰氯甲酯进行酰化反应，得到双(新戊酰氧基甲基)PMEA（2）。该酯前药对单纯疱疹病毒2型（HSV-2）的体外效力增强，比母体化合物高150倍以上。化合物2对HSV-1的抗病毒活性比PMEA高50倍，对HIV和人巨细胞病毒（HCMV）的活性相当。在静息细胞和生长细胞中都研究了化合物2的毒性。

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