Document Report Card

ID: ALA1123192

Journal: J Med Chem

Title: Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol.

Authors: Asselin AA, Humber LG, Crosilla D, Oshiro G, Wojdan A, Grimes D, Heaslip RJ, Rimele TJ, Shaw CC.

Abstract: The synthesis of 5-[hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]-1H-indole-7- carboxamide, 5, a pyrrolo analogue of labetalol, is described. Compound 5 was found to reduce blood pressure in spontaneously hypertensive rats with an ED50 of 5 mg/kg po, without causing any decrease in heart rate. Isolated tissue studies with 5 shows that it is a nonselective beta-adrenoceptor antagonist and that it is a weaker alpha-adrenoceptor antagonist with a relative selectivity for alpha 1-receptors. Additionally, the compound displayed significant beta-adrenoceptor intrinsic sympathomimetic activity. Evidence is presented that the beta-adrenoceptor antagonist and agonist properties of 5 are mediated via hydrogen-bond formation with the receptor.

CiteXplore: 3012084

DOI: 10.1021/jm00156a019