Indole-phenol-bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analog of labetalol
- 1 June 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 29 (6) , 1009-1015
- https://doi.org/10.1021/jm00156a019
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.This publication has 11 references indexed in Scilit:
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