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Article: Design, synthesis, and structure-activity relationships of a new series of α-adrenergic agonists: Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(1',2',3',4'- tetrahydronaphthalene)]

TitleDesign, synthesis, and structure-activity relationships of a new series of α-adrenergic agonists: Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(1',2',3',4'- tetrahydronaphthalene)]
Authors
Issue Date1995
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
Citation
Journal Of Medicinal Chemistry, 1995, v. 38 n. 20, p. 4056-4069 How to Cite?
AbstractThe contractions induced by a partial α1-adrenoceptor agonist in cutaneous veins, such as the saphenous vein, show a particular sensitivity to changes in local temperature: the contractility to a partial α1- adrenoceptor agonist increases when the temperature is raised, a response that contrasts to that noted with full α1- and α2-adrenoceptor agonists. This observation may be of importance for the treatment of the symptoms of venous insuffiency, favored during warm summer days. A new series of full and partial α-adrenergic agonists was designed and synthesized, the spiro[(1,3- diazacyclopent-1-ene)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]7a-kk or spiro-imidazolines. Using in vitro (femoral artery and saphenous vein) and in vivo (pithed rat) biological evaluations, structure-activity relationships could be defined which allowed the discovery of a full α2-agonist (34b), a full α1-agonist (7s), and a nonselective partial α1/α2-agonist (7aa) endowed with an outstanding veinotonic selectivity as compared to its effect on mean arterial pressure. The latter compound is presently undergoing extensive pharmacological and toxicological evaluations, as a clinical candidate.
Persistent Identifierhttp://hdl.handle.net/10722/171152
ISSN
2015 Impact Factor: 5.589
2015 SCImago Journal Rankings: 2.529
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCordi, AAen_US
dc.contributor.authorLacoste, JMen_US
dc.contributor.authorDescombes, JJen_US
dc.contributor.authorCourchay, Cen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorLaubie, Men_US
dc.contributor.authorVerbeuren, TJen_US
dc.date.accessioned2012-10-30T06:12:25Z-
dc.date.available2012-10-30T06:12:25Z-
dc.date.issued1995en_US
dc.identifier.citationJournal Of Medicinal Chemistry, 1995, v. 38 n. 20, p. 4056-4069en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://hdl.handle.net/10722/171152-
dc.description.abstractThe contractions induced by a partial α1-adrenoceptor agonist in cutaneous veins, such as the saphenous vein, show a particular sensitivity to changes in local temperature: the contractility to a partial α1- adrenoceptor agonist increases when the temperature is raised, a response that contrasts to that noted with full α1- and α2-adrenoceptor agonists. This observation may be of importance for the treatment of the symptoms of venous insuffiency, favored during warm summer days. A new series of full and partial α-adrenergic agonists was designed and synthesized, the spiro[(1,3- diazacyclopent-1-ene)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]7a-kk or spiro-imidazolines. Using in vitro (femoral artery and saphenous vein) and in vivo (pithed rat) biological evaluations, structure-activity relationships could be defined which allowed the discovery of a full α2-agonist (34b), a full α1-agonist (7s), and a nonselective partial α1/α2-agonist (7aa) endowed with an outstanding veinotonic selectivity as compared to its effect on mean arterial pressure. The latter compound is presently undergoing extensive pharmacological and toxicological evaluations, as a clinical candidate.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmcen_US
dc.relation.ispartofJournal of Medicinal Chemistryen_US
dc.subject.meshAdrenergic Alpha-Agonists - Chemical Synthesis - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDogsen_US
dc.subject.meshImidazoles - Chemical Synthesis - Pharmacologyen_US
dc.subject.meshMaleen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.titleDesign, synthesis, and structure-activity relationships of a new series of α-adrenergic agonists: Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(1',2',3',4'- tetrahydronaphthalene)]en_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/jm00020a021en_US
dc.identifier.pmid7562941-
dc.identifier.scopuseid_2-s2.0-0028838408en_US
dc.identifier.volume38en_US
dc.identifier.issue20en_US
dc.identifier.spage4056en_US
dc.identifier.epage4069en_US
dc.identifier.isiWOS:A1995RY25500021-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCordi, AA=7003462164en_US
dc.identifier.scopusauthoridLacoste, JM=7103018360en_US
dc.identifier.scopusauthoridDescombes, JJ=6602832507en_US
dc.identifier.scopusauthoridCourchay, C=6507690963en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridLaubie, M=7006492390en_US
dc.identifier.scopusauthoridVerbeuren, TJ=7007006534en_US

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