Imidazoline binding sites (IBS) profile modulation:: Key role of the bridge in determining I1-IBS or I2-IBS selectivity within a series of 2-phenoxymethylimidazoline analogues

被引：31

作者：

Gentili, F

Bousquet, P

Brasili, L

Dontenwill, M

Feldman, J

Ghelfi, F

Giannella, M

Piergentili, A

Quaglia, W

Pigini, M

机构：

[1] Univ Camerino, Dipartimento Sci Chim, I-62032 Camerino, Italy

[2] Univ Strasbourg 1, Lab Neurobiol & Pharmacol Cardiovasc, F-67000 Strasbourg, France

[3] Univ Modena, Dipartimento Sci Farmaceut, I-41100 Modena, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 11期

关键词：

D O I：

10.1021/jm021113r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The alpha- and beta-methyl derivatives of 2-phenylethylimidazoline (compounds 7 and 8) and the corresponding enantiomers were prepared and tested with the purpose of studying the role played by the ethylene bridge in modulating I-1- and I-2-IBS selectivity. The alpha-methylation appeared to be extremely critical regarding the affinity and selectivity for the I-1-IBS subtypes (I-1/I-2 = 186 for imidazoline 7) and the stereospecificity of interaction (eudismic ratio (S)-(-)7/(R)-(+)-7 = 5888). Instead, even if in a more limited fashion, the P-methylation tended toward I-2-IBS selectivity (I2I1 = 50 for imidazoline 8). The unsubstituted compound 4 (I-2/I-1 = 1479) proved to be considerably more potent and selective with respect to I-2-IBS subtypes.

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页码：2169 / 2176

页数：8

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