Synthesis and dopamine receptor modulating activity of 3-substituted γ-lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide

被引：45

作者：

Dolbeare, K

Pontoriero, GF

Gupta, SK

Mishra, RK

Johnson, RL ^{[1
]}

机构：

[1] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA

[2] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 05期

关键词：

D O I：

10.1021/jm020441o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

gamma-Lactam. peptidomimetic 2 of Pro-Leu-Gly-NH2 (PLG) was substituted at the 3-position with isobutyl, butyl, and benzyl moieties to give the PLG peptidomimetics 3-5, respectively. These compounds were synthesized to test the hypothesis that attaching a hydrophobic moiety to the lactam ring to mimic the isobutyl side chain of the leucyl residue of PLG would increase the dopamine receptor modulating activity of such peptidomimetics. These peptidomimetics were tested for their ability to enhance the binding of [H-3]-N-propylnorapomorphine to dopamine receptors isolated from bovine striatal membranes. The rank order of effectiveness of the 3-substituent was benzyl > n-butyl > isobutyl > H.

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页码：727 / 733

页数：7

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