Literature DB >> 17477516

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.

Gerard M P Giblin1, Celestine T O'Shaughnessy, Alan Naylor, William L Mitchell, Andrew J Eatherton, Brian P Slingsby, D Anthony Rawlings, Paul Goldsmith, Andrew J Brown, Carl P Haslam, Nick M Clayton, Alex W Wilson, Iain P Chessell, Andrew R Wittington, Richard Green.   

Abstract

Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.

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Year:  2007        PMID： 17477516     DOI： 10.1021/jm061195+

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  28 in total

1.  The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief.

Authors:  Jenny L Wilkerson; Erin D Milligan
Journal:  ISRN Anesthesiol       Date:  2011

2.  Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.

Authors:  Ai-Ling Li; Xiaoyan Lin; Amey S Dhopeshwarkar; Ana Carla Thomaz; Lawrence M Carey; Yingpeng Liu; Spyros P Nikas; Alexandros Makriyannis; Ken Mackie; Andrea G Hohmann
Journal:  Mol Pharmacol       Date:  2018-11-30       Impact factor: 4.436

3.  CoMFA and CoMSIA analyses on 1,2,3,4-tetrahydropyrrolo[3,4-b]indole and benzimidazole derivatives as selective CB2 receptor agonists.

Authors:  Elena Cichero; Sara Cesarini; Luisa Mosti; Paola Fossa
Journal:  J Mol Model       Date:  2010-02-20       Impact factor: 1.810

4.  In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models.

Authors:  B B Yao; G C Hsieh; J M Frost; Y Fan; T R Garrison; A V Daza; G K Grayson; C Z Zhu; M Pai; P Chandran; A K Salyers; E J Wensink; P Honore; J P Sullivan; M J Dart; M D Meyer
Journal:  Br J Pharmacol       Date:  2007-11-12       Impact factor: 8.739

5.  Synthesis and pharmacology of 1-deoxy analogs of CP-47,497 and CP-55,940.

Authors:  John W Huffman; Alicia L S Thompson; Jenny L Wiley; Billy R Martin
Journal:  Bioorg Med Chem       Date:  2007-09-22       Impact factor: 3.641

Review 6.  An overview of the cannabinoid type 2 receptor system and its therapeutic potential.

Authors:  Bihua Bie; Jiang Wu; Joseph F Foss; Mohamed Naguib
Journal:  Curr Opin Anaesthesiol       Date:  2018-08       Impact factor: 2.706

Review 7.  Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain.

Authors:  J Guindon; A G Hohmann
Journal:  Br J Pharmacol       Date:  2007-11-12       Impact factor: 8.739

8.  Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists.

Authors:  Matteo Gianella-Borradori; Ivy Christou; Carole J R Bataille; Rebecca L Cross; Graham M Wynne; David R Greaves; Angela J Russell
Journal:  Bioorg Med Chem       Date:  2014-11-08       Impact factor: 3.641

9.  Antinociceptive effects of tetrazole inhibitors of endocannabinoid inactivation: cannabinoid and non-cannabinoid receptor-mediated mechanisms.

Authors:  S Maione; E Morera; I Marabese; A Ligresti; L Luongo; G Ortar; V Di Marzo
Journal:  Br J Pharmacol       Date:  2008-07-28       Impact factor: 8.739

10.  Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors.

Authors:  Peng Yang; Kyaw-Zeyar Myint; Qin Tong; Rentian Feng; Haiping Cao; Abdulrahman A Almehizia; Mohammed Hamed Alqarni; Lirong Wang; Patrick Bartlow; Yingdai Gao; Jürg Gertsch; Jumpei Teramachi; Noriyoshi Kurihara; Garson David Roodman; Tao Cheng; Xiang-Qun Xie
Journal:  J Med Chem       Date:  2012-10-31       Impact factor: 7.446
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