Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Bioorg Med Chem. 2010 Feb;18(3):1076-82. doi: 10.1016/j.bmc.2009.12.046. Epub 2009 Dec 23.
On the basis of the previous results on a histamine H(4) receptor agonist 4-methylhistamine and a cyclopropane-based conformationally restricted analog CEIC (3) with potent H(3)/H(4) receptor antagonistic effect, 4-methylhistamine analogs 4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity (K(i)=38.7 nM) for the H(3) receptor, which was more potent than a well-known H(3) antagonist thioperamide. Stable tautomer and conformation of 3 and 4, which can affect the pharmacological activity, were analyzed by ab initio calculations.
基于先前关于组氨酸 H(4) 受体激动剂 4-甲基组氨酸和具有强效 H(3)/H(4) 受体拮抗作用的环丙烷基构象受限类似物 CEIC（3）的研究结果，设计并合成了 CEIC 的 4-甲基组氨酸类似物 4 和 5。化合物 4 对 H(3) 受体表现出强亲和力（K(i)=38.7 nM），比著名的 H(3) 拮抗剂噻哌酰胺更有效。通过从头计算分析了 3 和 4 的稳定互变异构体和构象，它们可以影响药理学活性。
