IRAK-4 inhibitors.: Part III:: A series of imidazo[1,2-a] pyridines

被引:51
作者
Buckley, George M. [1 ]
Fosbeary, Richard [1 ]
Fraser, Joanne L. [1 ]
Gowers, Lewis [1 ]
Higueruelo, Alicia P. [1 ]
James, Lynwen A. [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 ]
机构
[1] UCB, Cambridge CB21 6GS, England
关键词
IRAK; IRAK-4; inhibitor; kinase; kinase inhibitor; imidazo[1,2-a] pyridine; inflammation; anti-inflammatory; ligand efficiency; IL-1; TNF-alpha; TNF alpha; immunity;
D O I
10.1016/j.bmcl.2008.04.042
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Following the identification of a potent IRAK inhibitor through routine project cross screening, a novel class of IRAK-4 inhibitor was established. The SAR of imidazo[1,2-a] pyridino-pyridines and benzimidazolo-pyridines was explored. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3656 / 3660
页数:5
相关论文
共 13 条
  • [1] BUCKLEY GM, 2008, BIOORG MED CHEM LETT
  • [2] Reactivity of 3-iodoimidazo[1,2-a]pyridines using a Suzuki-type cross-coupling reaction
    Enguehard, C
    Renou, JL
    Collot, V
    Hervet, M
    Rault, S
    Gueiffier, A
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2000, 65 (20) : 6572 - 6575
  • [3] Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes
    Hollenberg, PF
    [J]. DRUG METABOLISM REVIEWS, 2002, 34 (1-2) : 17 - 35
  • [4] Ligand efficiency: a useful metric for lead selection
    Hopkins, AL
    Groom, CR
    Alex, A
    [J]. DRUG DISCOVERY TODAY, 2004, 9 (10) : 430 - 431
  • [5] The influence of drug-like concepts on decision-making in medicinal chemistry
    Leeson, Paul D.
    Springthorpe, Brian
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (11) : 881 - 890
  • [6] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
    Lipinski, CA
    Lombardo, F
    Dominy, BW
    Feeney, PJ
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 1997, 23 (1-3) : 3 - 25
  • [7] Azaindole derivatives with high affinity for the dopamine D4 receptor:: Synthesis, ligand binding studies and comparison of molecular electrostatic potential maps
    Löber, S
    Hübner, H
    Gmeiner, P
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (01) : 97 - 102
  • [8] The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling
    Lye, E
    Mirtsos, C
    Suzuki, N
    Suzuki, S
    Yeh, WC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (39) : 40653 - 40658
  • [9] Global mapping of pharmacological space
    Paolini, Gaia V.
    Shapland, Richard H. B.
    van Hoorn, Willem P.
    Mason, Jonathan S.
    Hopkins, Andrew L.
    [J]. NATURE BIOTECHNOLOGY, 2006, 24 (07) : 805 - 815
  • [10] Roberts WG, 2005, CANCER RES, V65, P957