Document Detail

Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol.
MedLine Citation:
PMID:  3012084     Owner:  NLM     Status:  MEDLINE    
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.
A A Asselin; L G Humber; D Crosilla; G Oshiro; A Wojdan; D Grimes; R J Heaslip; T J Rimele; C C Shaw
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  29     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1986 Jun 
Date Detail:
Created Date:  1986-07-07     Completed Date:  1986-07-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1009-15     Citation Subset:  IM    
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MeSH Terms
Antihypertensive Agents / chemical synthesis,  pharmacology*
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Guinea Pigs
Heart Rate / drug effects
Hydrogen Bonding
Labetalol / analogs & derivatives*
Rats, Inbred SHR
Receptors, Adrenergic, beta / drug effects
Structure-Activity Relationship
Reg. No./Substance:
0/Antihypertensive Agents; 0/Receptors, Adrenergic, beta; 36894-69-6/Labetalol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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