doi: 10.1021/jm8002203. Epub 2008 Jul 31.
Design and synthesis of a novel series of N-alkyl isatin acylhydrazone derivatives that act as selective cannabinoid receptor 2 agonists for the treatment of neuropathic pain
Affiliations
- PMID:18666769
- DOI: 10.1021/jm8002203
Item in Clipboard
Design and synthesis of a novel series of N-alkyl isatin acylhydrazone derivatives that act as selective cannabinoid receptor 2 agonists for the treatment of neuropathic pain
Philippe Diaz et al. J Med Chem..
Display options
Format
Display options
Format
Abstract
There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain. We have synthesized a novel series of N-alkyl isatin acylhydrazone derivatives and have identified and characterized several of them as novel analogues with high functional activity and selectivity at human CB2 receptors using [(35)S]GTP-gamma-S assays. Binding affinities at human CB2 and CB1 were determined for compounds 28, 33, 40, 48, and 58. Structure-activity relationship studies of this novel series led to optimization of our lead compound, compound 33 (MDA19). Compound 33 possessed potent antiallodynic effects in a rat model of neuropathic pain but did not affect rat locomotor activity. More potent and more CB2-receptor-selective compounds, including compounds 37, 40, and 48, were also discovered.
Similar articles
- 6-Methoxy-N-alkyl isatin acylhydrazone derivatives as a novel series of potent selective cannabinoid receptor 2 inverse agonists: design, synthesis, and binding mode prediction.Diaz P, Phatak SS, Xu J, Astruc-Diaz F, Cavasotto CN, Naguib M.Diaz P, et al.J Med Chem. 2009 Jan 22;52(2):433-44. doi: 10.1021/jm801353p.J Med Chem. 2009.PMID:19115816
- Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists.Chu GH, Saeui CT, Worm K, Weaver DG, Goodman AJ, Broadrup RL, Cassel JA, DeHaven RN, LaBuda CJ, Koblish M, Brogdon B, Smith S, Le Bourdonnec B, Dolle RE.Chu GH, et al.Bioorg Med Chem Lett. 2009 Oct 15;19(20):5931-5. doi: 10.1016/j.bmcl.2009.08.063. Epub 2009 Aug 21.Bioorg Med Chem Lett. 2009.PMID:19736007
- Discovery and optimization of a novel series of N-arylamide oxadiazoles as potent, highly selective and orally bioavailable cannabinoid receptor 2 (CB2) agonists.Cheng Y, Albrecht BK, Brown J, Buchanan JL, Buckner WH, DiMauro EF, Emkey R, Fremeau RT Jr, Harmange JC, Hoffman BJ, Huang L, Huang M, Lee JH, Lin FF, Martin MW, Nguyen HQ, Patel VF, Tomlinson SA, White RD, Xia X, Hitchcock SA.Cheng Y, et al.J Med Chem. 2008 Aug 28;51(16):5019-34. doi: 10.1021/jm800463f. Epub 2008 Aug 5.J Med Chem. 2008.PMID:18680277
- Latest advances in cannabinoid receptor agonists.Thakur GA, Tichkule R, Bajaj S, Makriyannis A.Thakur GA, et al.Expert Opin Ther Pat. 2009 Dec;19(12):1647-73. doi: 10.1517/13543770903436505.Expert Opin Ther Pat. 2009.PMID:19939187Review.
- Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--a short review.Svízenská I, Dubový P, Sulcová A.Svízenská I, et al.Pharmacol Biochem Behav. 2008 Oct;90(4):501-11. doi: 10.1016/j.pbb.2008.05.010.Pharmacol Biochem Behav. 2008.PMID:18584858Review.
Cited by
- Design, synthesis, binding and docking-based 3D-QSAR studies of 2-pyridylbenzimidazoles--a new family of high affinity CB1 cannabinoid ligands.Mella-Raipán JA, Lagos CF, Recabarren-Gajardo G, Espinosa-Bustos C, Romero-Parra J, Pessoa-Mahana H, Iturriaga-Vásquez P, Pessoa-Mahana CD.Mella-Raipán JA, et al.Molecules. 2013 Apr 4;18(4):3972-4001. doi: 10.3390/molecules18043972.Molecules. 2013.PMID:23558540Free PMC article.
- 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists: design, synthesis, and binding mode prediction through ligand-steered modeling.Diaz P, Phatak SS, Xu J, Fronczek FR, Astruc-Diaz F, Thompson CM, Cavasotto CN, Naguib M.Diaz P, et al.ChemMedChem. 2009 Oct;4(10):1615-29. doi: 10.1002/cmdc.200900226.ChemMedChem. 2009.PMID:19637157Free PMC article.
- Design and evaluation of a novel fluorescent CB2 ligand as probe for receptor visualization in immune cells.Petrov RR, Ferrini ME, Jaffar Z, Thompson CM, Roberts K, Diaz P.Petrov RR, et al.Bioorg Med Chem Lett. 2011 Oct 1;21(19):5859-62. doi: 10.1016/j.bmcl.2011.07.099. Epub 2011 Aug 3.Bioorg Med Chem Lett. 2011.PMID:21855337Free PMC article.
- Prevention of paclitaxel-induced neuropathy through activation of the central cannabinoid type 2 receptor system.Naguib M, Xu JJ, Diaz P, Brown DL, Cogdell D, Bie B, Hu J, Craig S, Hittelman WN.Naguib M, et al.Anesth Analg. 2012 May;114(5):1104-20. doi: 10.1213/ANE.0b013e31824b0191. Epub 2012 Mar 5.Anesth Analg. 2012.PMID:22392969Free PMC article.
- Exploring the effectiveness of novel benzimidazoles as CB2 ligands: synthesis, biological evaluation, molecular docking studies and ADMET prediction.Tonelli M, Cichero E, Mahmoud AM, Rabbito A, Tasso B, Fossa P, Ligresti A.Tonelli M, et al.Medchemcomm. 2018 Oct 10;9(12):2045-2054. doi: 10.1039/c8md00461g. eCollection 2018 Dec 1.Medchemcomm. 2018.PMID:30647880Free PMC article.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information