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9-芳基嘌呤的高效合成及抗肠道病毒活性。

Efficient synthesis and anti-enteroviral activity of 9-arylpurines.

机构信息

Instituto de Química Médica (IQM-CSIC), Madrid, Spain.

出版信息

Eur J Med Chem. 2012 Mar;49:279-88. doi: 10.1016/j.ejmech.2012.01.022. Epub 2012 Jan 17.

Abstract

To further explore the anti-enteroviral activity of 9-aryl-6-chloropurines, three different series of compounds with a dialkylamino, (alkyl)amido, or oxazolidinone substituent at the aryl ring have been synthesized, in most cases with the aid of microwave-assisted synthesis. The resulting compounds efficiently inhibit Coxsackie virus type B3 (CVB3) replication with EC(50) values varying from 3 to 15 μM, and with no significant toxicity in Vero cells. The most potent compounds also selectively inhibit the replication of other enteroviruses including Coxsackie virus B4 and Echo virus 11. The cross-resistance studies performed with different 9-aryl-6-chloropurines indicate that they all belong to the same pharmacological family and differ from other CVB3 drugs such as enviroxime.

摘要

为了进一步探索 9-芳基-6-氯嘌呤的抗肠道病毒活性,我们合成了三个不同系列的化合物,这些化合物在芳环上带有二烷基氨基、(烷基)酰胺基或恶唑烷酮取代基,大多数情况下借助微波辅助合成。结果表明,这些化合物能够有效地抑制柯萨奇病毒 B3(CVB3)的复制,EC50 值在 3 到 15 μM 之间,对 Vero 细胞没有明显的毒性。最有效的化合物还能选择性地抑制其他肠道病毒(包括柯萨奇病毒 B4 和埃可病毒 11)的复制。对不同的 9-芳基-6-氯嘌呤进行的交叉耐药性研究表明,它们都属于同一类药理学家族,与其他 CVB3 药物(如依诺昔姆)不同。

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