Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase

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dc.contributor.author Selwood, David en_US
dc.contributor.author Brummell, David en_US
dc.contributor.author Budworth, Joanna en_US
dc.contributor.author Burtin, Guillaume en_US
dc.contributor.author Campbell, Richard en_US
dc.contributor.author Chana, Surinder en_US
dc.contributor.author Charles, Ian en_US
dc.contributor.author Fernandez, Patricia en_US
dc.contributor.author Glen, Robert en_US
dc.contributor.author Goggin, Maria en_US
dc.contributor.author Hobbs, Adrian en_US
dc.contributor.author Kling, Marcel en_US
dc.contributor.author Liu, Qian en_US
dc.contributor.author Madge, David en_US
dc.contributor.author Meillerais, Sylvie en_US
dc.contributor.author Powell, Kenneth en_US
dc.contributor.author Reynolds, Karen en_US
dc.contributor.author Spacey, Graham en_US
dc.contributor.author Stables, Jeremy en_US
dc.contributor.author Tatlock, Mark en_US
dc.contributor.author Wheeler, Kerry en_US
dc.contributor.author Wishart, Grant en_US
dc.contributor.author Woo, Chi-Kit en_US
dc.contributor.editor en_US
dc.date.accessioned 2011-02-07T06:19:07Z
dc.date.available 2011-02-07T06:19:07Z
dc.date.issued 2001 en_US
dc.identifier 2009005025 en_US
dc.identifier.citation Selwood David et al. 2001, 'Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase', American Chemical Society, vol. 44, pp. 78-93. en_US
dc.identifier.issn 0022-2623 en_US
dc.identifier.other C1UNSUBMIT en_US
dc.identifier.uri http://hdl.handle.net/10453/13142
dc.description.abstract Database searching and compound screening identified !-benzyl-3-(3-dimethylaminopropyloxy). indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A ?ompr~hensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However' replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing)no significant inhibition of phosphodiesterases or nitric oxide synthases. en_US
dc.language en_US
dc.publisher American Chemical Society en_US
dc.relation.isbasedon http://dx.doi.org/10.1021/jm001034k en_US
dc.title Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase en_US
dc.parent Journal Of Medicinal Chemistry en_US
dc.journal.volume 44 en_US
dc.journal.number en_US
dc.publocation United States en_US
dc.identifier.startpage 78 en_US
dc.identifier.endpage 93 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 030400 en_US
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dc.personcode 0000061985 en_US
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dc.percentage 100 en_US
dc.classification.name Medicinal and Biomolecular Chemistry en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords NA en_US
dc.staffid en_US


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