Sriram Dharmarajan, Yogeeswari Perumal, Myneedu Naga Sirisha, Saraswat Vivek
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, India.
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2127-9. doi: 10.1016/j.bmcl.2006.01.050. Epub 2006 Feb 3.
The synthesis of a new series of abacavir prodrugs involving N2-substitution with various substituted benzaldehyde and ketone derivatives is described. The in vitro anti-HIV activities indicated that compound (3-(2-(4-methylaminobenzylideneamino)-6-(cyclopropylamino)-9H-purin-9-yl)cyclopentyl)methanol (3) was found to be most potent compound with EC50 of 0.05 microM and CC50 of >100 microM with selectivity index of >2000. Compound 3 was found to be 32 times more potent than the parent drug (EC50 of 1.6 microM). At pH 7.4, 37 degrees C, the hydrolytic t1/2 ranged between 120 and 240 min.
描述了一系列新的阿巴卡韦前药的合成，这些前药涉及用各种取代的苯甲醛和酮衍生物进行N2-取代。体外抗HIV活性表明，化合物（3-(2-(4-甲基氨基亚苄基氨基)-6-(环丙基氨基)-9H-嘌呤-9-基)环戊基）甲醇（3）是最有效的化合物，其EC50为0.05微摩尔，CC50大于100微摩尔，选择性指数大于2000。发现化合物3的效力比母体药物高32倍（EC50为1.6微摩尔）。在pH 7.4、37℃下，水解半衰期在120至240分钟之间。
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