Document Report Card

ID: ALA1134368

Journal: J Med Chem

Title: Alpha(2) adrenoceptor agonists as potential analgesic agents. 3. Imidazolylmethylthiophenes.

Authors: Boyd RE, Press JB, Rasmussen CR, Raffa RB, Codd EE, Connelly CD, Li QS, Martinez RP, Lewis MA, Almond HR, Reitz AB.

Abstract: A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the alpha(2) adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the alpha(2D) adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED(50) doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4.

CiteXplore: 11300868

DOI: 10.1021/jm0003891