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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
23695049 - Dopaminergic symptoms in migraine.
7501649 - Role of 5-ht receptor subtypes in the modulation of dorsal periaqueductal gray generate...
1675609 - Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-ht1a rec...
25447299 - Delta opioid receptors expressed in forebrain gabaergic neurons are responsible for snc...
1886079 - Molecular design of novel ligands for 5-ht1a receptors.
8808139 - Elicited pgo waves in rats: lack of 5-ht1a inhibition in putative pontine generator reg...
9919489 - Alpha-tocopherol protects the peroxidative modification of ldl to be recognized by ldl ...
12832529 - Na-k-cl cotransporter contributes to glutamate-mediated excitotoxicity.
9519799 - Characterization of muscarinic receptors mediating the contraction of the urinary detru...
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    
Affiliation:
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / antagonists & inhibitors
Animals
Chemical Phenomena
Chemistry
Cyclization
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*
Rats
Receptors, Serotonin / drug effects,  physiology
Serotonin / pharmacology,  physiology*
Substantia Nigra / metabolism
Chemical
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 4.6.1.1/Adenylate Cyclase

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


Previous Document:  A simple method for mouse embryo cryopreservation in a low toxicity vitrification solution, without ...
Next Document:  Antiandrogenic steroidal sulfonylpyrazoles.