当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 2-[(4-phenylpiperazin-1-yl)methyl]imidazo(di)azines as selective D4-ligands. Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a potent and selective D4 partial agonist.

2-[(4-phenylpiperazin-1-yl)methyl]imidazo(di)azines as selective D4-ligands. Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a potent and selective D4 partial agonist.

Abstract：

:A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional experiments indicated neutral antagonists or weak partial agonist effects for most of the target compounds, the 2-methoxyphenyl substituted 2-piperazinylmethylimidazopyridine 3c (PIP3EA) displayed substantial agonist efficacy in mitogenesis experiments and GTPgammaS binding tests, resulting in EC50 values of 3.0 (46%) and 4.5 nM (57%), respectively. Our D4 agonist 3c induced penile erection in vivo when administered to rats. This effect was inhibited by L-745,870 a D4 selective antagonist, confirming the mechanistic pathway.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Enguehard-Gueiffier C,Hübner H,El Hakmaoui A,Allouchi H,Gmeiner P,Argiolas A,Melis MR,Gueiffier A

doi

10.1021/jm060166w

subject

Has Abstract

pub_date

2006-06-29 00:00:00

pages

3938-47

issue

13

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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