Source:http://linkedlifedata.com/resource/pubmed/id/20851599
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
2010-10-19
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pubmed:abstractText |
A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds' structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT(3) receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methyl-5-HT, which was expressed in the form of pA(2) value. All the synthesized compounds showed antagonism towards 5-HT(3) receptor; based on this result, a structure-activity relationship was derived, which reveals that the aromatic residue in 5-HT(3) receptor antagonists may have hydrophobic interaction with 5-HT(3) receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA(2) values exhibited good anti-depressant-like activity as compared to the vehicle-treated group.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1464-3405
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6773-6
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pubmed:meshHeading |
pubmed-meshheading:20851599-Amides,
pubmed-meshheading:20851599-Animals,
pubmed-meshheading:20851599-Depression,
pubmed-meshheading:20851599-Drug Design,
pubmed-meshheading:20851599-Guinea Pigs,
pubmed-meshheading:20851599-Mice,
pubmed-meshheading:20851599-Quinoxalines,
pubmed-meshheading:20851599-Receptors, Serotonin, 5-HT3,
pubmed-meshheading:20851599-Serotonin Antagonists,
pubmed-meshheading:20851599-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:20851599-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
Design, synthesis and structure-activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression.
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pubmed:affiliation |
Pharmacy Group, FD-III, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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