Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaline and quinazoline derivatives as CB2 receptor agonists

被引：85

作者：

Saari, Raimo ^{[1
]}

Torma, Jonna-Carita ^{[1
]}

Nevalainen, Tapio ^{[1
]}

机构：

[1] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, FIN-70211 Kuopio, Finland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 02期

基金：

芬兰科学院;

关键词：

Receptors; Agonists; Cannabinoid receptor 2; Quinoline; Isoquinoline; Quinoxaline; Quinazoline; Microwave irradiation; NEUROPATHIC PAIN; CANNABINOID CB1; LIGAND; IDENTIFICATION; ANTAGONISTS; ACTIVATION; KINASE;

D O I：

10.1016/j.bmc.2010.11.059

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [S-35]GTP gamma S binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC50 = 7.8; E-max = 75%). The isoquinolin-1-yl(3-trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC50 = 5.8; E-max = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC50 = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：939 / 950

页数：12

共 26 条

[1] Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective Agonists [J].

Ashton, John C. ;

Wright, Jason L. ;

McPartland, John M. ;

Tyndall, Joel D. A. .

CURRENT MEDICINAL CHEMISTRY, 2008, 15 (14) :1428-1443

[2] Some derivatives of isocoumarin and isocarbostyril. [J].

Bain, D ;

Perkin, WH ;

Robinson, R .

JOURNAL OF THE CHEMICAL SOCIETY, 1914, 105 :2392-2404

[3] Synthesis of a prodrug designed to release multiple inhibitors of the epidermal growth factor receptor tyrosine kinase and an alkylating agent: A novel tumor targeting concept [J].

Banerjee, R ;

Rachid, Z ;

McNamee, J ;

Jean-Claude, BJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (25) :5546-5551

[4]

Brewster R. Q., 1943, ORG SYNTH, V2, P445

[5] Synthesis of substituted pyridines by the reactions of halopyridines with sulfur, oxygen and carbon nucleophiles under focused microwave irradiation [J].

Cherng, YH .

TETRAHEDRON, 2002, 58 (24) :4931-4935

[6] Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists [J].

Chu, Guo-Hua ;

Saeui, Christopher T. ;

Worm, Karin ;

Weaver, Damian G. ;

Goodman, Allan J. ;

Broadrup, Robert L. ;

Cassel, Joel A. ;

DeHaven, Robert N. ;

LaBuda, Christopher J. ;

Koblish, Michael ;

Brogdon, Bernice ;

Smith, Steve ;

Le Bourdonnec, Bertrand ;

Dolle, Roland E. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (20) :5931-5935

[7] The synthesis of a novel inhibitor of B-Raf kinase [J].

Denni-Dischert, D ;

Marterer, W ;

Bänziger, M ;

Yusuff, N ;

Batt, D ;

Ramsey, T ;

Geng, P ;

Michael, W ;

Wang, RMB ;

Taplin, F ;

Versace, R ;

Cesarz, D ;

Perez, LB .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2006, 10 (01) :70-77

[8] Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naive rats and in rat models of inflammatory and neuropathic pain [J].

Elmes, SJR ;

Jhaveri, MD ;

Smart, D ;

Kendall, DA ;

Chapman, V .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 20 (09) :2311-2320

[9] Discovery of 2-[(2,4-Dichlorophenyl)amino]-N-[(tetrahydro-2H-pyran-4-yl)methyl]-4-(trifluoromethyl)-5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain [J].

Giblin, Gerard M. P. ;

O'Shaughnessy, Celestine T. ;

Naylor, Alan ;

Mitchell, William L. ;

Eatherton, Andrew J. ;

Slingsby, Brian P. ;

Rawlings, D. Anthony ;

Goldsmith, Paul ;

Brown, Andrew J. ;

Haslam, Carl P. ;

Clayton, Nick M. ;

Wilson, Alex W. ;

Chessell, Iain P. ;

Wittington, Andrew R. ;

Green, Richard .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (11) :2597-2600

[10] Discovery of 1-[4-(3-Chlorophenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a Brain Penetrant 5-Azaindole CB2 Agonist for the Treatment of Chronic Pain [J].

Giblin, Gerard M. P. ;

Billinton, Andrew ;

Briggs, Michael ;

Brown, Andrew J. ;

Chessell, Iain P. ;

Clayton, Nick M. ;

Eatherton, Andrew J. ;

Goldsmith, Paul ;

Haslam, Carl ;

Johnson, Matthew R. ;

Mitchell, William L. ;

Naylor, Alan ;

Perboni, Alcide ;

Slingsby, Brian P. ;

Wilson, Alex W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (19) :5785-5788

← 1 2 3 →