Phenylpyridine-2-ylguanidines and rigid mimetics as novel inhibitors of TNFα overproduction: Beneficial action in models of neuropathic pain and of acute lung inflammation

被引：14

作者：

Bollenbach, Maud ^{[1
,5
]}

Salvat, Eric ^{[2
,3
]}

Daubeuf, Francois ^{[1
,4
,5
]}

Wagner, Patrick ^{[1
,5
]}

Yalcin, Ipek ^{[2
]}

Humo, Muris ^{[2
]}

Letellier, Baptiste ^{[2
]}

Becker, Lea J. ^{[2
]}

Bihel, Frederic ^{[1
,5
]}

Bourguignon, Jean-Jacques ^{[1
,5
]}

Villa, Pascal ^{[4
,5
]}

Obrecht, Adeline ^{[4
,5
]}

Frossard, Nelly ^{[1
,5
]}

Barrot, Michel ^{[2
]}

Schmitt, Martine ^{[1
,5
]}

机构：

[1] Univ Strasbourg, CNRS, UMR7200, Lab Innovat Therapeut, F-67401 Illkirch Graffenstaden, France

[2] Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, F-67000 Strasbourg, France

[3] Hop Univ Strasbourg, Ctr Evaluat & Traitement Douleur, F-67000 Strasbourg, France

[4] Univ Strasbourg, CNRS, PCBIS Plateforme Chim Biol Integrat UMS3286, F-67400 Illkirch Graffenstaden, France

[5] Labex MEDALIS, F-67000 Strasbourg, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 147卷

关键词：

Pyridine-2-yl guanidine; TNF alpha inhibitor; Phenotypic screening; Inflammation; Neuropathic pain; NECROSIS-FACTOR-ALPHA; PHARMACOLOGICAL EVALUATION; NEUROPEPTIDE FF; ALPHA(2)-ADRENOCEPTOR ANTAGONISTS; RECEPTOR ANTAGONIST; CYCLIC GUANIDINES; MOUSE MODELS; RAT MODEL; DERIVATIVES; PENTOXIFYLLINE;

D O I：

10.1016/j.ejmech.2018.01.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-phenylpyridin-2-yl-guanidine (5b): a new inhibitor of the overproduction of pro-inflammatory cytokines (TNF alpha and Il1 beta) was identified from a high-throughput screening of a chemical library on human peripheral blood mononuclear cells (PBMCs) after LPS stimulation. Derivatives, homologues and rigid mimetics of 5b were designed and synthesized, and their cytotoxicity and ability to inhibit TNF alpha overproduction were evaluated. Among them, compound 5b and its mimetic 12 (2-aminodihydroquinazoline) showed similar inhibitory activities, and were evaluated in vivo in models of lung inflammation and neuropathic pain in mice. In particular, compound 12 proved to be active (5 mg/kg, ip) in both models. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：163 / 182

页数：20

共 78 条

[1]

Aggarwal BB, 2013, BRIT J PHARMACOL, V169, P1672, DOI DOI 10.1111/BPH.12131

[2] Elevated levels of tumor necrosis factor-α and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain [J].

Andrade, Pablo ;

Hoogland, Govert ;

Teernstra, Onno P. ;

van Aalst, Jasper ;

van Maren, Emiel ;

Daemen, Marc A. ;

Visser-Vandewalle, Veerle .

SPINE JOURNAL, 2016, 16 (02) :243-251

[3]

[Anonymous], 2013, GlaxoSmithKline Intellectual Property (No.2) Limited, Chemical compounds, Patent No. [WO2013062945, 2013062945]

[4] Synthesis and structure activity relationship of guanidines as NPYY5 antagonists [J].

Aquino, CJ ;

Ramanjulu, JM ;

Heyer, D ;

Daniels, AJ ;

Palazzo, F ;

Dezube, M .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (10) :2691-2708

[5] The neuro-immune balance in neuropathic pain: Involvement of inflammatory immune cells, immune-like glial cells and cytokines [J].

Austin, Paul J. ;

Moalem-Taylor, Gila .

JOURNAL OF NEUROIMMUNOLOGY, 2010, 229 (1-2) :26-50

[6] Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-pyridinylguanidines [J].

Barber, CG ;

Dickinson, RP ;

Horne, VA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (02) :181-184

[7] TESTS AND MODELS OF NOCICEPTION AND PAIN IN RODENTS [J].

Barrot, M. .

NEUROSCIENCE, 2012, 211 :39-50

[8] A facile reduction of 2-aminopyrimidines with triethylsilane and trifluoroacetic acid [J].

Baskaran, S ;

Hanan, E ;

Byun, D ;

Shen, W .

TETRAHEDRON LETTERS, 2004, 45 (10) :2107-2111

[9] Regulation of peroxisome proliferator-activated receptor-α expression during lung inflammation [J].

Becker, Julien ;

Delayre-Orthez, Carine ;

Frossard, Nelly ;

Pons, Francoise .

PULMONARY PHARMACOLOGY & THERAPEUTICS, 2008, 21 (02) :324-330

[10] Chronic, but not acute, tricyclic antidepressant treatment alleviates neuropathic allodynia after sciatic nerve cuffing in mice [J].

Benbouzid, Malika ;

Choucair-Jaafar, Nada ;

Yalcin, Ipek ;

Waltisperger, Elisabeth ;

Muller, Andre ;

Freund-Mercier, Marie Jose ;

Barrot, Michel .

EUROPEAN JOURNAL OF PAIN, 2008, 12 (08) :1008-1017

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