The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors that have potential value in the treatment of HIV/AIDS. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties. A series of novel ADAMs were therefore designed and synthesized in order to replace the metabolically labile methyl ester moieties of the existing ADAM lead compounds with hydrolytically stable, fused isoxazolone, isoxazole, oxazolone, or cyano substituents on the aromatic rings. The methyl ester and methoxy substituents on both of the aromatic rings in the parent compound 1 were successfully replaced with metabolically stable moieties with retention of anti-HIV activity and a general decrease in cytotoxicity.
-
【Replacement of the metabolically labile methyl esters in the alkenyldiarylmethane series of non-nucleoside reverse transcriptase inhibitors with isoxazolone, isoxazole, oxazolone, or cyano substituents.].
【用异恶唑酮，异恶唑，恶唑酮或氰基取代基代替非核苷类逆转录酶抑制剂的烯基二芳基甲烷系列中的代谢不稳定的甲酯。】
复制标题
收藏
DOI：10.1021/jm060449o文章类型：杂志文章
复制DOI
译文
：烯基二芳基甲烷（ADAM）是一类独特的非核苷类逆转录酶抑制剂，在治疗HIV / AIDS中具有潜在价值。然而，ADAM的潜在用途受到代谢不稳定的甲基酯部分的存在的限制。因此，设计并合成了一系列新颖的ADAM，以在芳香环上用水解稳定的稠合异恶唑酮，异恶唑，恶唑酮或氰基取代基取代现有ADAM铅化合物的代谢不稳定的甲基部分。母体化合物1的两个芳香环上的甲酯和甲氧基取代基均成功地被代谢稳定的部分所取代，并保留了抗HIV活性并普遍降低了细胞毒性。
