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

J Med Chem. 1986 Jun;29(6):1009-15. doi: 10.1021/jm00156a019.


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.

MeSH terms

  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart Rate / drug effects
  • Hydrogen Bonding
  • In Vitro Techniques
  • Labetalol / analogs & derivatives*
  • Rats
  • Rats, Inbred SHR
  • Receptors, Adrenergic, beta / drug effects
  • Structure-Activity Relationship


  • Antihypertensive Agents
  • Receptors, Adrenergic, beta
  • Labetalol