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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1987-10-9
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pubmed:abstractText |
cis-10-Hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b -octahydrobenzo[f]quinoline (4) is a centrally acting serotonin (5-HT) receptor agonist of moderate potency. Due to its semirigid character and the obvious similarity between (4aR,10bS)-4 and more potent, centrally acting 5-HT receptor agonist cis-(1S,2R)-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (2), we carried out the preparation (via resolution of 6, a precursor of 4) and the pharmacological testing of the enantiomers of 4. We were able to show that the active enantiomers of 4 and 2 coincide in terms of stereochemistry, i.e., that it is the 4aR,10bS enantiomer of 4 that is the more active one. The absolute configuration was assigned on the basis of single-crystal X-ray analysis of the precursor (+)-6 of the active enantiomer (-)-4. Conformational analysis with molecular mechanics (MM2) calculations were performed on the N-methyl analogues of compounds cis-(1S,2R)-2 (cis-(1S,2R)-3) and cis-(4aR,10bS)-4 (cis-(4aR,10bS)-7). Both ammonium and free amine forms were subjected to these calculations. The results show a preference for the N-equatorial conformation, which is corroborated by the X-ray structure of (+)-6.HCl. The relatively low potency of compound cis-(4aR,10bS)-4 might be explained by unfavorable direction of the N-lone pair (or ammonium hydrogen) bond in this compound as compared to cis-(1S,2R)-2 and trans-(4aR,10bR)-5, which can be predicted to be the more active enantiomer of compound 5.
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pubmed:grant | |
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 |
Sep
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1567-73
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:3625704-Animals,
pubmed-meshheading:3625704-Chemistry, Physical,
pubmed-meshheading:3625704-Hydroxyquinolines,
pubmed-meshheading:3625704-Male,
pubmed-meshheading:3625704-Models, Molecular,
pubmed-meshheading:3625704-Physicochemical Phenomena,
pubmed-meshheading:3625704-Rats,
pubmed-meshheading:3625704-Rats, Inbred Strains,
pubmed-meshheading:3625704-Receptors, Dopamine,
pubmed-meshheading:3625704-Receptors, Serotonin,
pubmed-meshheading:3625704-Serotonin,
pubmed-meshheading:3625704-Structure-Activity Relationship,
pubmed-meshheading:3625704-X-Ray Diffraction
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pubmed:year |
1987
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pubmed:articleTitle |
Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b- octahydrobenzo[f]quinoline : central serotonin stimulating properties.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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