NG-Acylated Imidazolylpropylguanidines as Potent Histamine H4 Receptor Agonists: Selectivity by Variation of the NG-Substituent

被引：47

作者：

Igel, Patrick ^{[1
]}

Schneider, Erich ^{[2
]}

Schnell, David ^{[2
]}

Elz, Sigurd ^{[1
]}

Seifert, Roland ^{[3
]}

Buschauer, Armin ^{[1
]}

机构：

[1] Univ Regensburg, Dept Pharmaceut Med Chem, Fac Chem & Pharm, D-93053 Regensburg, Germany

[2] Univ Regensburg, Dept Pharmacol & Toxicol, Fac Chem & Pharm, D-93053 Regensburg, Germany

[3] Hannover Med Sch, Inst Pharmacol, D-30625 Hannover, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 08期

关键词：

H-4-RECEPTOR AGONIST; 1ST POTENT; H-2-RECEPTOR; H-1-RECEPTOR; BINDING; H4;

D O I：

10.1021/jm9000693

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3-(1H-Imidazol-4-yl)propylguanidine (SK&F 91486, 4) was identified as a potent partial agonist at the human histamine H-3 receptor (hH(3)R) and human histamine H-4 receptor (hH(4)R). With the aim to increase selectivity for the hH4R, the guanidine group in 4 was acylated. N-1-Acetyl-N-2-[3-(1H-imidazol-4-yl)propyl]guanidine (UR-PI288, 13) was a potent full agonist at the hH(4)R (pEC(50) = 8.31; alpha = 1.00), possessing more than 1000- and 100-fold selectivity relative to the hH(1)R and hH(2)R, respectively, and possessing only low intrinsic activity (alpha = 0.27) at the hH(3)R.

引用

页码：2623 / 2627

页数：5

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