当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > High affinity ligands and potent antagonists for the α1D-adrenergic receptor. Novel 3,8-disubstituted [1]benzothieno[3,2-d]pyrimidine derivatives.

High affinity ligands and potent antagonists for the α1D-adrenergic receptor. Novel 3,8-disubstituted [1]benzothieno[3,2-d]pyrimidine derivatives.

Abstract：

:A new series of high affinity ligands and antagonists for the α1D-adrenergic receptor (AR) has been discovered. New molecules present a [1]benzothieno[3,2-d]pyrimidin-2,4(1H,3H)-dione or a [1]benzothieno[3,2-d]pyrimidin-4(3H)-one scaffold and bear a 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl moiety in the 3-position and various amide substituents in the 8-position. In binding assays at the three human cloned α1A-, α1B-, and α1D-AR subtypes, they showed high affinity values, particularly for the α1D-AR subtype. Compound 22 (RX18), N(1)-methyl-N(5)-[3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2,4-dioxo-1,2,3,4-tetrahydro[1]benzothieno[3,2-d]pyrimidin-8-yl]-N(1)-(phenylmethyl)pentanediamide, was the most interesting in the series displaying very high affinity (pKi = 10.25) and potent antagonism (pKb = 9.15) when tested in a functional assay at the α1D-AR.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Romeo G,Salerno L,Pittalà V,Modica MN,Siracusa MA,Materia L,Buccioni M,Marucci G,Minneman KP

doi

10.1016/j.ejmech.2014.06.057

subject

Has Abstract

pub_date

2014-08-18 00:00:00

pages

419-32

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00586-8

journal_volume

83

pub_type

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