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ID: ALA1134991

Journal: Bioorg Med Chem Lett

Title: Alpha(1)-adrenoceptor activation: a comparison of 4-(anilinomethyl)imidazoles and 4-(phenoxymethyl)imidazoles to related 2-imidazolines.

Authors: Hodson SJ, Bigham EC, Garrison DT, Gobel MJ, Irving PE, Liacos JA, Navas F, Saussy DL, Sherman BW, Speake JD, Bishop MJ.

Abstract: Literature reports suggest that disruption of an interhelical salt bridge is critical for alpha(1)-adrenoceptor activation, and the basic amine found in adrenergic receptor ligands is responsible for the disruption. Novel 4-(anilinomethyl)imidazoles and 4-(phenoxymethyl)imidazoles are agonists of the cloned human alpha(1)-adrenoceptors in vitro, and potent, selective alpha(1A)-adrenoceptor agonists have been identified in this series. These imidazoles demonstrate similar potencies and alpha(1)-subtype selectivities as the corresponding 2-substituted imidazolines. The extremely close SAR suggests that, in spite of the large difference in basicity, these imidazoles and imidazolines may establish the same interactions to activate alpha(1)-adrenoceptors.

CiteXplore: 12419381

DOI: 10.1016/s0960-894x(02)00753-9