Document Detail

3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.
MedLine Citation:
PMID:  2374139     Owner:  NLM     Status:  MEDLINE    
The synthesis and in vitro and in vivo characteristics of 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1, CP-93,129) are described. This rotationally restricted phenolic analogue of RU-24,969 is a potent (15 nM) and selective (200x vs the 5-HT1A receptor, 150x vs the 5HT1D receptor) functional agonist for the 5-HT1B receptor. Direct infusion of 1 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regulating feeding behavior in rodents. 3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1) has also been shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor. The source of the selectivity of 1 appears to lie in the ability of a pyrrolo[3,2-b]pyrid-5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole.
J E Macor; C A Burkhart; J H Heym; J L Ives; L A Lebel; M E Newman; J A Nielsen; K Ryan; D W Schulz; L K Torgersen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  33     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-08-30     Completed Date:  1990-08-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2087-93     Citation Subset:  IM    
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
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MeSH Terms
Adenylate Cyclase / antagonists & inhibitors
Chemical Phenomena
Eating / drug effects
Forskolin / pharmacology
Guinea Pigs
Hippocampus / enzymology
Indoles / pharmacology*
Molecular Structure
Paraventricular Hypothalamic Nucleus / drug effects,  physiology
Pyridines / chemical synthesis,  metabolism,  pharmacology*
Pyrroles / chemical synthesis,  metabolism,  pharmacology*
Receptors, Serotonin / drug effects,  physiology
Serotonin / pharmacology,  physiology*
Substantia Nigra / metabolism
Reg. No./Substance:
0/Indoles; 0/Pyridines; 0/Pyrroles; 0/Receptors, Serotonin; 127792-75-0/3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; 50-67-9/Serotonin; 66428-89-5/Forskolin; 74163-68-1/5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; EC Cyclase

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

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