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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1999-3-16
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pubmed:abstractText |
Clinically effective antimigraine drugs such as Sumatriptan have similar affinity at h5-HT1D and h5-HT1B receptors. In the search for a h5-HT1D-selective agonist as an antimigraine agent, a novel series of 3-(propylpiperazinyl)indoles have been synthesized and evaluated at h5-HT1D and h5-HT1B receptors. This class of compounds has provided subnanomolar, fully efficacious h5-HT1D agonists with up to 200-fold selectivity for the h5-HT1D receptor over the h5-HT1B receptor. Unlike other h5-HT1D-selective series, several propylpiperazines demonstrate good oral bioavailability. The optimum compound was 1-(3-[5-(1,2, 4-triazol-4-yl)-1H-indol-3-yl]propyl)-4-(2-(3-fluorophenyl)ethyl)p ipe razine (7f) which has excellent selectivity for h5-HT1D receptors over other 5-HT receptor subtypes and good oral bioavailability in three species. Compound 7f has been selected for further investigation as a potential development candidate in the treatment of migraine.
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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/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1D,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BeerM SMS,
pubmed-author:ChambersM SMS,
pubmed-author:GoodacreSS,
pubmed-author:HoltzD MDM,
pubmed-author:HungEE,
pubmed-author:JelleyR ARA,
pubmed-author:MacLeodA MAM,
pubmed-author:MatassaV GVG,
pubmed-author:RathboneDD,
pubmed-author:ReeveA JAJ,
pubmed-author:StantonJ AJA,
pubmed-author:SternfeldFF,
pubmed-author:StreetL JLJ,
pubmed-author:WattA PAP
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
691-705
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10052976-Administration, Oral,
pubmed-meshheading:10052976-Animals,
pubmed-meshheading:10052976-Biological Availability,
pubmed-meshheading:10052976-CHO Cells,
pubmed-meshheading:10052976-Cricetinae,
pubmed-meshheading:10052976-Indoles,
pubmed-meshheading:10052976-Male,
pubmed-meshheading:10052976-Migraine Disorders,
pubmed-meshheading:10052976-Models, Molecular,
pubmed-meshheading:10052976-Piperazines,
pubmed-meshheading:10052976-Radioligand Assay,
pubmed-meshheading:10052976-Rats,
pubmed-meshheading:10052976-Rats, Sprague-Dawley,
pubmed-meshheading:10052976-Receptor, Serotonin, 5-HT1B,
pubmed-meshheading:10052976-Receptor, Serotonin, 5-HT1D,
pubmed-meshheading:10052976-Receptors, Serotonin,
pubmed-meshheading:10052976-Recombinant Proteins,
pubmed-meshheading:10052976-Serotonin Receptor Agonists,
pubmed-meshheading:10052976-Structure-Activity Relationship
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pubmed:year |
1999
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pubmed:articleTitle |
3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents.
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pubmed:affiliation |
Department of Chemistry, Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, U.K.
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pubmed:publicationType |
Journal Article
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