α2 Adrenoceptor Agonists as Potential Analgesic Agents. 1. (Imidazolylmethyl)oxazoles and -thiazoles

A series of (imidazolylmethyl)oxazoles and -thiazoles were prepared and evaluated as α 2 adrenoceptor agonists. These compounds were also tested in in vivo paradigms that are predictive of analgesic activity. Variations in both the imidazole and thiazole portions of the molecule were investigated. Some of the more potent compounds such as 22, 26, 45, and 53 displayed α 2 receptor binding in the 10-20 nM range and also had significant antinociceptive activity in the mouse abdominal irritant test (MAIT).