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rdf:type |
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lifeskim:mentions |
umls-concept:C0035647,
umls-concept:C0040616,
umls-concept:C0063510,
umls-concept:C0205314,
umls-concept:C0220781,
umls-concept:C0243076,
umls-concept:C0597357,
umls-concept:C0600115,
umls-concept:C0679622,
umls-concept:C0887819,
umls-concept:C1883254
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pubmed:issue |
10
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pubmed:dateCreated |
1998-5-28
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pubmed:abstractText |
The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Anxiety Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BaileyFF,
pubmed-author:BlackburnT PTP,
pubmed-author:BlaneyF EFE,
pubmed-author:BromidgeS MSM,
pubmed-author:DabbsSS,
pubmed-author:DaviesD TDT,
pubmed-author:DuckworthD MDM,
pubmed-author:ForbesI TIT,
pubmed-author:HamPP,
pubmed-author:HollandVV,
pubmed-author:JonesG EGE,
pubmed-author:KennettG AGA,
pubmed-author:KingF DFD,
pubmed-author:NaylorC BCB,
pubmed-author:RileyG JGJ,
pubmed-author:SaundersD VDV,
pubmed-author:StarrSS,
pubmed-author:ThewlisK MKM,
pubmed-author:WoodM DMD,
pubmed-author:WymanP APA
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1598-612
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:9572885-Animals,
pubmed-meshheading:9572885-Anti-Anxiety Agents,
pubmed-meshheading:9572885-Conditioning, Operant,
pubmed-meshheading:9572885-Conflict (Psychology),
pubmed-meshheading:9572885-Indoles,
pubmed-meshheading:9572885-Male,
pubmed-meshheading:9572885-Models, Molecular,
pubmed-meshheading:9572885-Motor Activity,
pubmed-meshheading:9572885-Pyridines,
pubmed-meshheading:9572885-Rats,
pubmed-meshheading:9572885-Rats, Sprague-Dawley,
pubmed-meshheading:9572885-Receptor, Serotonin, 5-HT2B,
pubmed-meshheading:9572885-Receptor, Serotonin, 5-HT2C,
pubmed-meshheading:9572885-Receptors, Serotonin,
pubmed-meshheading:9572885-Serotonin Antagonists,
pubmed-meshheading:9572885-Social Behavior,
pubmed-meshheading:9572885-Structure-Activity Relationship
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pubmed:year |
1998
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pubmed:articleTitle |
Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines.
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pubmed:affiliation |
SmithKline Beecham Pharmaceuticals, Discovery Research, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, England.
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pubmed:publicationType |
Journal Article
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