| pubmed-article:9484496 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C0021242 | lld:lifeskim |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C0025219 | lld:lifeskim |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C0065911 | lld:lifeskim |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C1441547 | lld:lifeskim |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C0682770 | lld:lifeskim |
| pubmed-article:9484496 | lifeskim:mentions | umls-concept:C1283195 | lld:lifeskim |
| pubmed-article:9484496 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:9484496 | pubmed:dateCreated | 1998-3-17 | lld:pubmed |
| pubmed-article:9484496 | pubmed:abstractText | Tetrahydrocyclopent[b]indoles, tetrahydrocarbazoles, and hexahydrocyclohept[b]indoles have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was compared in a radioligand binding assay using chicken brain membranes and agonist and antagonist potency measured in clonal Xenopus laevis melanophore cells. Comparison of the N-acyl-3-amino-6-methoxytetrahydrocarbazoles (2) with N-acyl-4-(aminomethyl)-6-methoxy-9-methyltetrahydrocarbazoles (9) showed that the latter have much higher binding affinities for the chicken brain receptor. Comparison of N-acyl-1-(aminomethyl)-7-methoxy-4-methyltetrahydrocyclopent[b]ind oles (10), 6-methoxytetrahydrocarbazoles (9), and N-acyl-10-(aminomethyl)-2-methoxy-5-methylhexahydrocyclohept[b]ind oles (11) showed that the tetrahydrocarbazoles had the highest binding affinity with the cyclohept[b]indoles and the cyclopent[b]indoles having rather lower affinities. All of these observations are in agreement with our postulated model of melatonin orientation at the binding pocket in which the 3-amidoethane side chain is in a conformation close to the 5-methoxyl group, as is shown in the X-ray crystallographic structure of 9m and in the energy-minimized computed structures. Separation of the enantiomers of members from each of these three systems was accomplished by chiral HPLC. It was found that in all cases the (-)-enantiomer had a higher binding affinity than the (+)-enantiomer. An X-ray crystallographic analysis of the two enantiomers of 9a showed that the (+)-enantiomer had the (R) absolute stereochemistry. Since the sign of the Cotton curves, determined from circular dichroism studies, was the same for all (+)-enantiomers, it is assumed that the absolute stereochemistry at these centers is identical. In the Xenopus melanophore assay, the tetrahydrocarbazoles 2 (R = H) were mainly weak antagonists, while those with R = OMe were agonists. The biological behavior of the tetrahydrocarbazoles 9 (R = H) depended on R1, some being agonists and some antagonists, whereas those with R = OMe were generally agonists. Variation of the R and R1 groups in compounds of type 9 produced both agonists and antagonists. The tetrahydrocylopentaindoles 10 had similar biological properties to the corresponding analogues of 9, but the hexahydrocycloheptaindoles 11 showed a much greater propensity to be antagonists. In all cases the (S)-enantiomers were found to be more potent agonists than the (R)-enantiomers. | lld:pubmed |
| pubmed-article:9484496 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9484496 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9484496 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9484496 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:9484496 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:DaviesD JDJ | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:DaviesJJ | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:SugdenDD | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:TocherD ADA | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:TanM JMJ | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:GarrettL JLJ | lld:pubmed |
| pubmed-article:9484496 | pubmed:author | pubmed-author:VonhoffSS | lld:pubmed |
| pubmed-article:9484496 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9484496 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:9484496 | pubmed:volume | 41 | lld:pubmed |
| pubmed-article:9484496 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9484496 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9484496 | pubmed:pagination | 451-67 | lld:pubmed |
| pubmed-article:9484496 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:9484496 | pubmed:meshHeading | pubmed-meshheading:9484496-... | lld:pubmed |
| pubmed-article:9484496 | pubmed:meshHeading | pubmed-meshheading:9484496-... | lld:pubmed |
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| pubmed-article:9484496 | pubmed:meshHeading | pubmed-meshheading:9484496-... | lld:pubmed |
| pubmed-article:9484496 | pubmed:year | 1998 | lld:pubmed |
| pubmed-article:9484496 | pubmed:articleTitle | Mapping the melatonin receptor. 5. Melatonin agonists and antagonists derived from tetrahydrocyclopent[b]indoles, tetrahydrocarbazoles and hexahydrocyclohept[b]indoles. | lld:pubmed |
| pubmed-article:9484496 | pubmed:affiliation | Department of Chemistry, University College London, U.K. | lld:pubmed |
| pubmed-article:9484496 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:9484496 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:9484496 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:9484496 | lld:pubmed |
