| pubmed-article:10425096 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0036751 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0038477 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C1510827 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0682770 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0728938 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0205549 | lld:lifeskim |
| pubmed-article:10425096 | lifeskim:mentions | umls-concept:C0243072 | lld:lifeskim |
| pubmed-article:10425096 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:10425096 | pubmed:dateCreated | 1999-8-31 | lld:pubmed |
| pubmed-article:10425096 | pubmed:abstractText | A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxamide derivatives bearing a piperazine moiety was synthesized. Their in vitro 5-HT(4), 5-HT(3), and D(2) receptors affinities were evaluated by radioligand binding assay. For selected compounds functional studies at the 5-HT(4) receptor were made by using precontracted (by carbachol) preparations of rat esophageal tunica muscularis mucosae (TMM). The influence of the 3-substituent of the benzimidazole ring, the 4-substituent of the piperazine moiety, and the alkylene spacer was studied. Compounds with an ethyl or a cyclopropyl substituent in the 3-position of the benzimidazole ring showed moderate to high affinity (K(i) = 6.7-75.4 nM) for the 5-HT(4) receptor with selectivity over 5-HT(3) and D(2) receptors and moderate antagonist activity (pK(b) = 6.19-7.73). Compounds with an isopropyl substituent in the 3-benzimidazole position exhibited moderate and selective 5-HT(4) affinity (K(i) >/= 38.9 nM) and a partial agonist activity (5a, i.a. = 0.94) higher than that of the reference compound BIMU 8 (i.a. = 0.70). This reversal of the pharmacological activity due only to a small structural difference might confirm the existence of two binding sites on the 5-HT(4) receptor. In the alkylene spacer, a two-methylene chain is favorable to optimize the affinity and the antagonist or the partial agonist activity. In the ethyl and cyclopropyl series, 5-HT(4) antagonist activity seems to be unrelated to the size of the 4-substituent of the piperazine moiety, whereas a methyl group is optimal for high partial agonist activity in the isopropyl series; however, the presence of a butyl substituent is a favorable pattern for 5-HT(4) antagonism and even causes a reversal of the pharmacological profile in the isopropyl series (5h, pK(b) = 7.94). N-Butyl quaternization of 5a led to an improvement in affinity for the 5-HT(4) receptor and mantained the high partial agonist activity (5r, K(i) = 66.3 nM, i.a. = 0.93). | lld:pubmed |
| pubmed-article:10425096 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10425096 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10425096 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10425096 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:10425096 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:TapiaII | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:LabeagaLL | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:OrjalesAA | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:MosqueraRR | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:Alonso-CiresL... | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:López-Tudanca... | lld:pubmed |
| pubmed-article:10425096 | pubmed:author | pubmed-author:InnerárityAA | lld:pubmed |
| pubmed-article:10425096 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10425096 | pubmed:day | 29 | lld:pubmed |
| pubmed-article:10425096 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:10425096 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10425096 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10425096 | pubmed:pagination | 2870-80 | lld:pubmed |
| pubmed-article:10425096 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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| pubmed-article:10425096 | pubmed:meshHeading | pubmed-meshheading:10425096... | lld:pubmed |
| pubmed-article:10425096 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10425096 | pubmed:articleTitle | 2,3-Dihydro-2-oxo-1H-benzimidazole-1-carboxamides with selective affinity for the 5-HT(4) receptor: synthesis and structure-affinity and structure-activity relationships of a new series of partial agonist and antagonist derivatives. | lld:pubmed |
| pubmed-article:10425096 | pubmed:affiliation | Departamento de Investigación, FAES, S.A., Máximo Aguirre 14, 48940 Leioa, Vizcaya, Spain. | lld:pubmed |
| pubmed-article:10425096 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10425096 | pubmed:publicationType | In Vitro | lld:pubmed |
| pubmed-article:10425096 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:10425096 | lld:chembl |
