Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: Effects of substitution about the rigidifying ring

被引：16

作者：

Koenig, John R. ^{[1
]}

Liu, Huaqing ^{[1
]}

Drizin, Irene ^{[1
]}

Witte, David G. ^{[1
]}

Carr, Tracy L. ^{[1
]}

Manelli, Arlene M. ^{[1
]}

Milicic, Ivan ^{[1
]}

Strakhova, Marina I. ^{[1
]}

Miller, Thomas R. ^{[1
]}

Esbenshade, Timothy A. ^{[1
]}

Brioni, Jorge D. ^{[1
]}

Cowart, Marlon ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Neurosci Res, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 06期

关键词：

Histamine; Histamine H-4 receptor; EOSINOPHIL CHEMOTAXIS; INFLAMMATION; ANTIHISTAMINES; CELLS; PAIN; RAT;

D O I：

10.1016/j.bmcl.2010.01.131

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Three novel series of histamine H-4 receptor (H4R) antagonists containing the 2-aminopyrimidine motif are reported. The best of these compounds display good in vitro potency in both functional and binding assays. In addition, representative compounds are able to completely block itch responses when dosed ip in a mouse model of H-4-agonist induced scratching, thus demonstrating their activities as H4R antagonists. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1900 / 1904

页数：5

共 21 条

[1] Histamine receptors are hot in immunopharmacology [J].

Akdis, CA ;

Simons, FER .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 533 (1-3) :69-76

[2] Histamine H3 Receptor: A Potential Drug Target for the Treatment of Central Nervous System Disorders [J].

Alguacil, L. F. ;

Perez-Garcia, C. .

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2003, 2 (05) :303-313

[3] Structure-Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H4 Receptor Ligands [J].

Altenbach, Robert J. ;

Adair, Ronald M. ;

Bettencourt, Brian M. ;

Black, Lawrence A. ;

Fix-Stenzel, Shannon R. ;

Gopalakrishnan, Suiatha M. ;

Hsieh, Gin C. ;

Liu, Huaqing ;

Marsh, Kennan C. ;

McPherson, Michael J. ;

Milicic, Ivan ;

Miller, Thomas R. ;

Vortherms, Timothy A. ;

Warrior, Usha ;

Wetter, Jill M. ;

Wishart, Neil ;

Witte, David G. ;

Honore, Prisca ;

Esbenshade, Timothy A. ;

Hancock, Arthur A. ;

Brioni, Jorge D. ;

Cowart, Marlon D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (20) :6571-6580

[4] Total synthesis of himachalene sesquiterpenes of Aphthona and Phyllotreta flea beetles [J].

Bartelt, RJ ;

Weisleder, D ;

Momany, FA .

SYNTHESIS-STUTTGART, 2003, (01) :117-123

[5] Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in BalbC mice [J].

Bell, JK ;

McQueen, DS ;

Rees, JL .

BRITISH JOURNAL OF PHARMACOLOGY, 2004, 142 (02) :374-380

[6] Histamine induces cytoskeletal changes in human eosinophils via the H4 receptor [J].

Buckland, KF ;

Williams, TJ ;

Conroy, DM .

BRITISH JOURNAL OF PHARMACOLOGY, 2003, 140 (06) :1117-1127

[7] Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation [J].

Coruzzi, Gabriella ;

Adami, Maristella ;

Guaita, Elena ;

de Esch, Lwan J. P. ;

Leurs, Rob .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2007, 563 (1-3) :240-244

[8] Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H4 Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models [J].

Cowart, Marlon D. ;

Altenbach, Robert J. ;

Liu, Huaqing ;

Hsieh, Gin C. ;

Drizin, Irene ;

Milicic, Ivan ;

Miller, Thomas R. ;

Witte, David G. ;

Wishart, Neil ;

Fix-Stenzel, Shannon R. ;

McPherson, Michael J. ;

Adair, Ronald M. ;

Wetter, Jill M. ;

Bettencourt, Brian M. ;

Marsh, Kerman C. ;

Sullivan, James P. ;

Honore, Prisca ;

Esbenshade, Timothy A. ;

Brioni, Jorge D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (20) :6547-6557

[9] Functional expression of H4 histamine receptor in human natural killer cells, monocytes, and dendritic cells [J].

Damaj, Bassam B. ;

Becerra, Cecilia Barrena ;

Esber, Henry J. ;

Wen, Ying ;

Maghazachi, Azzam A. .

JOURNAL OF IMMUNOLOGY, 2007, 179 (11) :7907-7915

[10] The histamine H4 receptor as a new therapeutic target for inflammation [J].

de Esch, IJP ;

Thurmond, RL ;

Jongejan, A ;

Leurs, R .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2005, 26 (09) :462-469

← 1 2 3 →