HOMOLOGS OF HISTAMINE AS HISTAMINE H-3 RECEPTOR ANTAGONISTS - A NEW POTENT AND SELECTIVE H-3 ANTAGONIST, 4(5)-(5-AMINOPENTYL)-1H-IMIDAZOLE

被引：39

作者：

VOLLINGA, RC

MENGE, WMPB

LEURS, R

TIMMERMAN, H

机构：

[1] Leiden / Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Department of Pharmacochemistry, 1081 HV Amsterdam, Vrije Universiteit Amsterdam

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 02期

关键词：

D O I：

10.1021/jm00002a008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The influence of alkyl chain length variation on the histamine H-3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H-3 activity, the affinities of these compounds for the H-1 and H-2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H-3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H-3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA(2) value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.

引用

页码：266 / 271

页数：6

共 21 条

[1] THE SYNTHESIS OF UNSATURATED FATTY ACIDS [J].

AHMAD, K ;

STRONG, FM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1948, 70 (05) :1699-1700

[2]

AKABORI S, 1932, J CHEM SOC JPN, V53, P207

[3] AUTO-INHIBITION OF BRAIN HISTAMINE-RELEASE MEDIATED BY A NOVEL CLASS (H-3) OF HISTAMINE-RECEPTOR [J].

ARRANG, JM ;

GARBARG, M ;

SCHWARTZ, JC .

NATURE, 1983, 302 (5911) :832-837

[4] HIGHLY POTENT AND SELECTIVE LIGANDS FOR HISTAMINE RECEPTORS-H-3 [J].

ARRANG, JM ;

GARBARG, M ;

LANCELOT, JC ;

LECOMTE, JM ;

POLLARD, H ;

ROBBA, M ;

SCHUNACK, W ;

SCHWARTZ, JC .

NATURE, 1987, 327 (6118) :117-123

[5] 2,5-DILITHIATION OF N-PROTECTED IMIDAZOLES - SYNTHESES OF 2,5-DISUBSTITUTED DERIVATIVES OF 1-METHOXYMETHYL-IMIDAZOLE, 1-TRIPHENYLMETHYL-IMIDAZOLE, AND 1-(N,N-DIMETHYLSULPHONAMIDO)-IMIDAZOLE [J].

CHADWICK, DJ ;

NGOCHINDO, RI .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1984, (03) :481-486

[6] IMETIT AND N-METHYL DERIVATIVES - THE TRANSITION FROM POTENT AGONIST TO ANTAGONIST AT HISTAMINE H-3 RECEPTORS [J].

GANELLIN, CR ;

BANGANDERSEN, B ;

KHALAF, YS ;

TERTIUK, W ;

ARRANG, JM ;

GARBARG, M ;

LIGNEAU, X ;

ROULEAU, A ;

SCHWARTZ, JC .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (10) :1231-1234

[7]

GARBARG M, 1992, J PHARMACOL EXP THER, V263, P304

[8]

Gibson M. S., 1968, ANGEW CHEM-GER EDIT, V80, P986

[9] 2 NOVEL, POTENT AND SELECTIVE HISTAMINE H-3 RECEPTOR AGONISTS [J].

HOWSON, W ;

PARSONS, ME ;

RAVAL, P ;

SWAYNE, GTG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (01) :77-78

[10] PHARMACOLOGICAL CHARACTERIZATION OF THE HUMAN HISTAMINE H-2-RECEPTOR STABLY EXPRESSED IN CHINESE-HAMSTER OVARY CELLS [J].

LEURS, R ;

SMIT, MJ ;

MENGE, WMBP ;

TIMMERMAN, H .

BRITISH JOURNAL OF PHARMACOLOGY, 1994, 112 (03) :847-854

← 1 2 3 →