Isothiourea analogues of histamine as potent agonists or antagonists of the histamine H3-receptor

Article abstract of DOI:10.1016/0223-5234(92)90185-4

The synthesis and H₃-activity of a series of isothiourea analogues of histamine have been described. It has been shown that S-[2-(4(5)-imidazolyl)ethylisothiourea (VUF 8325) is a potent H₃-agonist measured as the electrically evoked contraction of the guinea-pig ileum. Upon methylation of the imidazole system or the isothiourea moiety a decrease in affinity was observed leading to either weak agonists or weak antagonists. Introduction of N-(phenylalkyl) substituents at the isothiourea part gives rise to highly potent H₃-antagonists. Particularly the 4-chlorobenzyl group appeared to be favourable in the series described resulting in a histamine H₃-antagonist with a pA₂-value of 9.9.