Optimization of a series of quinazolinone-derived antagonists of CXCR3

被引：32

作者：

Liu, Jiwen ^{[1
]}

Fu, Zice ^{[1
]}

Li, An-Rong ^{[1
]}

Johnson, Michael ^{[1
]}

Zhu, Liusheng ^{[1
]}

Marcus, Andrew ^{[1
]}

Danao, Jay ^{[1
]}

Sullivan, Tim ^{[1
]}

Tonn, George ^{[1
]}

Collins, Tassie ^{[1
]}

Medina, Julio ^{[1
]}

机构：

[1] Amgen Inc, 1120 Vet Blvd, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

CXCR3; IP10; ITAC; MIG; CXCL9; CXCL10; CXCL11; Chemokine receptor; GPCR; Antagonist; Quinazolinone; SAR; CHEMOKINE RECEPTOR CXCR3; MULTIPLE-SCLEROSIS; EXPRESSION; IDENTIFICATION; DERIVATIVES; DISCOVERY; FLUORINE; CXCL10; IP-10;

D O I：

10.1016/j.bmcl.2009.07.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5114 / 5118

页数：5

共 32 条

[1] CXCR3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection
Agostini, C
Calabrese, F
Rea, F
Facco, M
Tosoni, A
Loy, M
Binotto, G
Valente, M
Trentin, L
Semenzato, G
[J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (05) : 1703 - 1711
[2] Identification and structure-activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists
Allen, Daniel R.
Bolt, Amanda
Chapman, Gayle A.
Knight, Roland L.
Meissner, Johannes W. G.
Owen, David A.
Watson, Robert J.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (03) : 697 - 701
[3] Palladium-catalysed α-arylation of esters and amides under microwave conditions
Bentz, E
Moloney, MG
Westaway, SM
[J]. TETRAHEDRON LETTERS, 2004, 45 (40) : 7395 - 7397
[4] Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists
Bongartz, Jean-Pierre
Buntinx, Mieke
Coesemans, Erwin
Hermans, Bart
Van Lommen, Guy
Van Wauwe, Jean
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (21) : 5819 - 5823
[5] Gene Expression Analysis of Host Innate Immune Responses during Lethal H5N1 Infection in Ferrets
Cameron, Cheryl M.
Cameron, Mark J.
Bermejo-Martin, Jesus F.
Ran, Longsi
Xu, Luoling
Turner, Patricia V.
Ran, Ran
Danesh, Ali
Fang, Yuan
Chan, Pak-Kei M.
Mytle, Nutan
Sullivan, Timothy J.
Collins, Tassie L.
Johnson, Michael G.
Medina, Julio C.
Rowe, Thomas
Kelvin, David J.
[J]. JOURNAL OF VIROLOGY, 2008, 82 (22) : 11308 - 11317
[6] Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonists
Cole, AG
Stroke, IL
Brescia, MR
Simhadri, S
Zhang, JJ
Hussain, Z
Snider, M
Haskell, C
Ribeiro, S
Appell, KC
Henderson, I
Webb, ML
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (01) : 200 - 203
[7] COLLINS TL, 2007, CHEMOKINE BIOL BASIC, V2, P79
[8] DETECTION OF A GAMMA-INTERFERON-INDUCED PROTEIN IP-10 IN PSORIATIC PLAQUES
GOTTLIEB, AB
LUSTER, AD
POSNETT, DN
CARTER, DM
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 168 (03) : 941 - 948
[9] The many roles for fluorine in medicinal chemistry
Hagmann, William K.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (15) : 4359 - 4369
[10] Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3
Hayes, Martin E.
Breinlinger, Eric C.
Wallace, Grier A.
Grongsaard, Pintipa
Miao, Wenyan
McPherson, Michael J.
Stoffel, Robert H.
Green, David W.
Roth, Gregory P.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (07) : 2414 - 2419

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