Author/Authors :
Stephen J. Hodson، نويسنده , , Eric C. Bigham، نويسنده , , Deanna T. Garrison، نويسنده , , Michael J. Gobel، نويسنده , , Paul E. Irving، نويسنده , , James A. Liacos، نويسنده , , Frank Navas III، نويسنده , , David L. Saussy Jr.، نويسنده , , Bryan W. Sherman، نويسنده , , Jason D. Speakeand، نويسنده , , Michael J. Bishop، نويسنده ,
Abstract :
Literature reports suggest that disruption of an interhelical salt bridge is critical for α1-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 α1-adrenoceptors in vitro, and potent, selective α1A-adrenoceptor agonists have been identified in this series. These imidazoles demonstrate similar potencies and α1-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 α1-adrenoceptors.
