HISTAMINE ANALOGS .33. 2-PHENYLHISTAMINES WITH HIGH HISTAMINE H-1-AGONISTIC ACTIVITY

被引：36

作者：

ZINGEL, V ^{[1
]}

ELZ, S ^{[1
]}

SCHUNACK, W ^{[1
]}

机构：

[1] FREE UNIV BERLIN, FAC PHARM, KONIGIN LUISE STR 2&4, W-1000 BERLIN 33, GERMANY

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 25卷 / 08期

关键词：

2-phenylhistamines; H[!sub]1[!/sub]-agonists; histamine H[!sub]1[!/sub]-receptor;

D O I：

10.1016/0223-5234(90)90132-M

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Phenylhistamines with various substituents at the phenyl ring were synthesized and the influence of substitution in ortho, meta or para position on histamine H1-agonistic activity was investigated. Compounds with high activity occurred in the meta phenyl series. Increased activity in the guinea-pig ileum assay was achieved by monosubstitution with halogen on the phenyl ring. 2-[2-(3-Fluorophenyl)-4-imidazolyl]ethanamine (12) is the most potent highly selective H1-agonist known so far, showing 87% relative potency compared with histamine and full efficacy at the H1-receptor. Relative activities of the 3-chloro analogue (11) and the 3-methyl analogue (13) are 81% and 29%, respectively. Histamine H2-activity could not be detected. 2-Phenylhistamines are available via reaction of the corresponding benzimidates with 2-oxo-4-phthalimido-1-butyl acetate (6) in liquid ammonia. © 1990.

引用

页码：673 / 680

页数：8

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