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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
20
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pubmed:dateCreated |
1992-12-18
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pubmed:abstractText |
A series of rotationally restricted phenolic analogs of the neurotransmitter serotonin has been synthesized with the 5-hydroxyindole portion of serotonin replaced by a dihydropyrano[3,2-e]-indole (1, 3, 4, and 5) and a dihydropyrano[2,3-f]indole (2). The receptor binding profile of these compounds has been studied and compared to the natural substrate serotonin. The dihydropyrano[3,2-e]indole derivatives (1, 3, 4, and 5) possess lower affinity for 5-HT1 receptors but equal or greater affinity for 5-HT2 receptors. Like serotonin, these compounds dose-dependently stimulated phosphatidylinositol turnover in rat brain slices. Moreover, the response to 1-(2-aminoethyl)-3-methyl-8,9-dihydropyrano[3,2-]indole (5, CP-132,484) and 1-(2-aminoethyl)-8,9-dihydropyrano[3,2-e]indole (4) is selectively antagonized by 5-HT2 receptor antagonists establishing these tryptamines as selective 5-HT2 receptor agonists. The high affinity and potency of 5 for 5-HT2 receptors suggests that the C5-hydroxy group in serotonin can function as a hydrogen bond acceptor in a 5-HT2 receptor with a directionality of interaction which is down and away from C6 in serotonin (Figure 5). Furthermore, the potent affinity of these compounds for 5-HT2 receptors coupled with their poor affinity for 5-HT1 receptors indicates that the aminoethyl side chain of serotonin adopts significantly different conformations in 5-HT1 versus 5-HT2 receptors.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(1,2,5,6-tetrahydropyrid-4-yl)pyrr...,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3625-32
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:1433172-Animals,
pubmed-meshheading:1433172-Indoles,
pubmed-meshheading:1433172-Pyridines,
pubmed-meshheading:1433172-Pyrroles,
pubmed-meshheading:1433172-Rats,
pubmed-meshheading:1433172-Receptors, Serotonin,
pubmed-meshheading:1433172-Serotonin,
pubmed-meshheading:1433172-Serotonin Receptor Agonists,
pubmed-meshheading:1433172-Structure-Activity Relationship
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pubmed:year |
1992
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pubmed:articleTitle |
1-(2-Aminoethyl)-3-methyl-8,9-dihydropyrano[3,2-e]indole: a rotationally restricted phenolic analog of the neurotransmitter serotonin and agonist selective for serotonin (5-HT2-type) receptors.
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pubmed:affiliation |
Department of Medicinal Chemistry, Pfizer, Inc., Groton, Connecticut 06340.
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pubmed:publicationType |
Journal Article
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