IRAK-4 inhibitors. Part 1: A series of amides

被引：36

作者：

Buckley, George M. ^{[1
]}

Gowers, Lewis ^{[1
]}

Higueruelo, Alicia Perez ^{[1
]}

Jenkins, Kerry ^{[1
]}

Mack, Stephen R. ^{[1
]}

Morgan, Trevor ^{[1
]}

Parry, David M. ^{[1
]}

Pitt, William R. ^{[1
]}

Rausch, Oliver ^{[1
]}

Richard, Marianna D. ^{[1
]}

Sabin, Verity ^{[1
]}

Fraser, Joanne L. ^{[1
]}

机构：

[1] UCB, Dept Med Chem, Cambridge CB21 6GS, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 11期

关键词：

IRAK; IRAK-4; inhibitor; inflammation; kinase; SAR; thiazole amide; pyridine amide; Suzuki reaction; docking; microsomes; solubility; in vivo exposure;

D O I：

10.1016/j.bmcl.2008.04.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and pro. le of a series of amides are described. Some of these compounds were potent IRAK-4 inhibitors and two examples were evaluated in vivo. (C) 2008 Elsevier Ltd. All rights reserved.

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页码：3211 / 3214

页数：4

相关论文

共 11 条

[1]

BUCKLEY GM, IN PRESS BIOORG MED

[2] Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members [J].

Janssens, S ;

Beyaert, R .

MOLECULAR CELL, 2003, 11 (02) :293-302

[3] Development and validation of a genetic algorithm for flexible docking [J].

Jones, G ;

Willett, P ;

Glen, RC ;

Leach, AR ;

Taylor, R .

JOURNAL OF MOLECULAR BIOLOGY, 1997, 267 (03) :727-748

[4] IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase [J].

Li, SY ;

Strelow, A ;

Fontana, EJ ;

Wesche, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5567-5572

[5] IRAK4 in TLR/IL-1R signaling: Possible clinical applications [J].

Li, Xiaoxia .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (03) :614-618

[6] Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections [J].

Medvedev, AE ;

Lentschat, A ;

Kuhns, DB ;

Blanco, JCG ;

Salkowski, C ;

Zhang, SL ;

Arditi, MH ;

Gallin, JI ;

Vogel, SN .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (04) :521-531

[7] Pyogenic bacterial infections in humans with IRAK-4 deficiency [J].

Picard, C ;

Puel, A ;

Bonnet, M ;

Ku, CL ;

Bustamante, J ;

Yang, K ;

Soudais, C ;

Dupuis, S ;

Feinberg, J ;

Fieschi, C ;

Elbim, C ;

Hitchcock, R ;

Lammas, D ;

Davies, G ;

Al-Ghonaium, A ;

Al-Rayes, H ;

Al-Jumaah, S ;

Al-Hajjar, S ;

Al-Mohsen, IZ ;

Frayha, HH ;

Rucker, R ;

Hawn, TR ;

Aderem, A ;

Tufenkeji, H ;

Haraguchi, S ;

Day, NK ;

Good, RA ;

Gougerot-Pocidalo, MA ;

Ozinsky, A ;

Casanova, JL .

SCIENCE, 2003, 299 (5615) :2076-2079

[8] Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4 [J].

Powers, JP ;

Li, SY ;

Jaen, JC ;

Liu, JQ ;

Walker, NPC ;

Wang, ZL ;

Wesche, H .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (11) :2842-2845

[9] COMPARATIVE PROTEIN MODELING BY SATISFACTION OF SPATIAL RESTRAINTS [J].

SALI, A ;

BLUNDELL, TL .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (03) :779-815

[10] Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4 [J].

Suzuki, N ;

Suzuki, S ;

Duncan, GS ;

Millar, DG ;

Wada, T ;

Mirtsos, C ;

Takada, H ;

Wakeham, A ;

Itie, A ;

Li, SY ;

Penninger, JM ;

Wesche, H ;

Ohashi, PS ;

Mak, TW ;

Yeh, WC .

NATURE, 2002, 416 (6882) :750-754