Aslanian R, Brown J E, Shih N Y, wa Mutahi M, Green M J, She S, Del Prado M, West R, Hey J
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 1998 Aug 18;8(16):2263-8. doi: 10.1016/s0960-894x(98)00399-0.
A series of amidine substituted phenyl-, benzyl-, and phenethylimidazoles based on the known H3 agonist SK&F 91606 (4) has been synthesized and tested as ligands for the histamine H3 receptor. Insertion of a phenyl ring between the imidazole ring and the amidine moiety produces antagonists. The benzyl series was found to be the most potent and was further investigated. Compounds 9c and 18 (entries 5 and 12, Table 1) are potent ligands for the H3 receptor with K(i) values of 16 nM and 7.2 nM respectively. In vivo, both compounds were shown to be equipotent to thioperamide (2), the standard H3 antagonist.
基于已知的H3激动剂SK&F 91606（4），合成了一系列脒取代的苯基、苄基和苯乙基咪唑，并作为组胺H3受体的配体进行了测试。在咪唑环和脒部分之间插入一个苯环会产生拮抗剂。发现苄基系列活性最强，并对其进行了进一步研究。化合物9c和18（表1中的第5项和第12项）是H3受体的强效配体，K(i)值分别为16 nM和7.2 nM。在体内，这两种化合物均显示出与标准H3拮抗剂硫代哌啶（2）等效。
