PMID: 3012084Jun 1, 1986Paper

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

Journal of Medicinal Chemistry
A A AsselinC C Shaw

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.

Citations

Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Xue-Mei Yang
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Xue-Mei Yang
Oct 11, 2017·Molecular Diversity·Jamatsing D RajputRatnamala S Bendre

Related Concepts

Antihypertensive Agents
Diastolic Blood Pressure
Dose-Response Relationship, Drug
Cavia porcellus
Pulse Rate
Hydrogen Bonding
Presolol
Rats, Inbred SHR
Beta-adrenergic receptor
Structure-Activity Relationship

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