Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol.
Article Details
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Asselin AA, Humber LG, Crosilla D, Oshiro G, Wojdan A, Grimes D, Heaslip RJ, Rimele TJ, Shaw CC
Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol.
J Med Chem. 1986 Jun;29(6):1009-15.
- PubMed ID
- 3012084 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Labetalol Beta-1 adrenergic receptor Kd (nM) 31.62 N/A N/A Details