Ishimata Nao, Ito Hideyuki, Tai Akihiro
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3533-6. doi: 10.1016/j.bmcl.2016.06.028. Epub 2016 Jun 11.
Methyl vanillate (1) showed strong degranulation inhibitory activity among vanillin derivatives tested. In order to find structure-activity relationships for developing anti-allergic agents with simple structures and potent activity, we synthesized several vanillic acid (VA) ester derivatives with C1-C4 and C8 alkyl chains and evaluated their degranulation inhibitory activities. The most active compound of VA ester derivatives was derivative 5 with a C4 straight alkyl chain, and derivative 5 exhibited approximately three-fold greater inhibitory activity than that of 1. Moreover, we designed 8 types of analogs based on 5, and we found that the minimum structure for potent degranulation inhibitory activity requires direct connection of the butyl ester moiety on the benzene ring and at least one hydroxyl group on the benzene ring. Butyl meta or para hydroxyl benzoate (10 or 11) has a simpler structure than that of 5 and exhibited more potent degranulation inhibitory activity than that of 5.
香草酸甲酯（1）在所测试的香草醛衍生物中表现出很强的脱颗粒抑制活性。为了找到结构-活性关系，以开发结构简单且活性强的抗过敏剂，我们合成了几种具有C1-C4和C8烷基链的香草酸（VA）酯衍生物，并评估了它们的脱颗粒抑制活性。VA酯衍生物中活性最高的化合物是具有C4直链烷基的衍生物5，衍生物5的抑制活性比1高约三倍。此外，我们基于5设计了8种类似物，发现具有强效脱颗粒抑制活性的最小结构要求苯环上的丁酯部分直接相连且苯环上至少有一个羟基。间位或对位羟基苯甲酸丁酯（10或11）的结构比5更简单，且表现出比5更强的脱颗粒抑制活性。
