| pubmed-article:10632037 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C0038477 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C2917246 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C0178528 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C0053183 | lld:lifeskim |
| pubmed-article:10632037 | lifeskim:mentions | umls-concept:C0243072 | lld:lifeskim |
| pubmed-article:10632037 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:10632037 | pubmed:dateCreated | 2000-2-14 | lld:pubmed |
| pubmed-article:10632037 | pubmed:abstractText | New benzimidazole-4-carboxamides 1-16 and -carboxylates 17-26 were synthesized and evaluated for binding affinity at serotonergic 5-HT4 and 5-HT3 receptors in the CNS. Most of the synthesized compounds exhibited moderate-to-very high affinity (in many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor. SAR observations and structural analyses (molecular modeling, INSIGHT II) indicated that the presence of a voluminous substituent in the basic nitrogen atom of the amino moiety and a distance of ca. 8.0 A from this nitrogen to the aromatic ring are of great importance for high affinity and selectivity for 5-HT4 receptors. These results confirm our recently proposed model for recognition by the 5-HT4 binding site. Amides 12-15 and esters 24 and 25 bound at central 5-HT4 sites with very high affinity (Ki = 0.11-2.9 nM) and excellent selectivity over serotonin 5-HT3, 5-HT2A, and 5-HT1A receptors (Ki > 1000-10,000 nM). Analogues 12 (Ki(5-HT4) = 0.32 nM), 13 (Ki(5-HT4) = 0.11 nM), 14 (Ki(5-HT4) = 0.29 nM) and 15 (Ki(5-HT4) = 0.54 nM) were pharmacologically characterized as selective 5-HT4 antagonists in the isolated guinea pig ileum (pA2 = 7.6, 7.9, 8.2 and 7.9, respectively), with a potency comparable to the 5-HT4 receptor antagonist RS 39604 (pA2 = 8.2). The benzimidazole-4-carboxylic acid derivatives described in this paper represent a novel class of potent and selective 5-HT4 receptor antagonists. In particular, compounds 12-15 could be interesting pharmacological tools for the understanding of the role of 5-HT4 receptors. | lld:pubmed |
| pubmed-article:10632037 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10632037 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10632037 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10632037 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:10632037 | pubmed:issn | 0968-0896 | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:MartínM IMI | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:AlfaroM JMJ | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:VisoAA | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:MorcilloM JMJ | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:MurciaMM | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:OrensanzLL | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:López-Rodrígu... | lld:pubmed |
| pubmed-article:10632037 | pubmed:author | pubmed-author:BenhamúBB | lld:pubmed |
| pubmed-article:10632037 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10632037 | pubmed:volume | 7 | lld:pubmed |
| pubmed-article:10632037 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10632037 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10632037 | pubmed:pagination | 2271-81 | lld:pubmed |
| pubmed-article:10632037 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
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| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
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| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
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| pubmed-article:10632037 | pubmed:meshHeading | pubmed-meshheading:10632037... | lld:pubmed |
| pubmed-article:10632037 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10632037 | pubmed:articleTitle | Benzimidazole derivatives. Part 1: Synthesis and structure-activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists. | lld:pubmed |
| pubmed-article:10632037 | pubmed:affiliation | Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain. mluzlr@eucmax.sim.ucm.es | lld:pubmed |
| pubmed-article:10632037 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10632037 | pubmed:publicationType | In Vitro | lld:pubmed |
| pubmed-article:10632037 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
