Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4732-5. doi: 10.1016/j.bmcl.2011.06.071. Epub 2011 Jun 23.
Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate.
氧化苦参碱（1）是一种天然抗乙型肝炎病毒（HBV）药物，它通过与核苷不同的机制下调宿主热应激同源物 70（Hsc70）的表达。以 Hsc70 为靶点抗 HBV，设计、合成了 26 种新型 N-取代苦参碱类似物，并以 1 为先导化合物，对其调节 Hsc70mRNA 表达的活性进行了评价。构效关系研究表明：（i）11 位的羧基是活性所必需的；（ii）在 3 的 12 位氮原子上引入取代基，特别是取代苄基，可能显著提高活性。在这些类似物中，具有 N-对甲氧基苄基的化合物 9p 与 1 相比，具有增加的抗 HBV 作用。我们认为 9p 是一种很有前途的抗 HBV 候选药物。
