Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-adrenergic receptor blocking properties

dc.creatorRomeiro, Luiz A. S.
dc.creatorFerreira, Marcos da Silva
dc.creatorSilva, Leandro L. da
dc.creatorCastro, Helena C.
dc.creatorMiranda, Ana L P
dc.creatorSilva, Cláudia L. M.
dc.creatorNoël, François
dc.creatorNascimento, Jéssica B.
dc.creatorAraújo, Claudia V.
dc.creatorTibiriçá, Eduardo
dc.creatorBarreiro, Eliezer J.
dc.creatorFraga, Carlos A. M.
dc.date2018-11-27T12:57:26Z
dc.date2018-11-27T12:57:26Z
dc.date2011
dc.date.accessioned2023-09-26T23:42:09Z
dc.date.available2023-09-26T23:42:09Z
dc.identifierROMEIRO, Luiz A. S. et al. Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties. European Journal of Medicinal Chemistry, v.46, p.3000-3012, April 2011.
dc.identifier0223-5234
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/30241
dc.identifier10.1016/j.ejmech.2011.04.032
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8893325
dc.descriptionWe described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [(3)H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (K(i) = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (K(B) = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (K(B) = 0.017 nM).
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectN-fenilpiperazina
dc.subjectAntagonista alfa-adrenoceptor
dc.subjectHiperplasia benigna da próstata
dc.subjectN-Phenylpiperazine
dc.subjectAlpha-adrenoceptor antagonist
dc.subjectBenign prostatic hyperplasia
dc.subjectSafrole, 1,3-Benzodioxole
dc.subjectHiperplasia Prostática
dc.subjectSafrol
dc.titleDiscovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-adrenergic receptor blocking properties
dc.typeArticle


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