Synthesis, in vitro and in vivo evaluation of 1,3,5-triazines as cannabinoid CB2 receptor agonists

European Journal of Pharmaceutical Sciences

Volumn 67, Issue , 2015, Pages 85-96

  Yrjölä, Sari ^a   Sarparanta, Mirkka ^b   Airaksinen, Anu J ^b   Hytti, Maria ^a   Kauppinen, Anu ^a,c   Pasonen Seppänen, Sanna ^a   Adinolfi, Barbara ^d,e   Nieri, Paola ^e   Manera, Clementina ^e   Keinänen, Outi ^b   Poso, Antti ^a,f   Nevalainen, Tapio J ^a   Parkkari, Teija ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

^b UNIVERSITY OF HELSINKI   (Finland)

^c KUOPIO UNIVERSITY HOSPITAL   (Finland)

^d CNR   (Italy)

^e UNIVERSITY OF PISA   (Italy)

^f UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

Cannabinoid receptor; CB2R agonists; Radioligand; Triazines

Indexed keywords

4 [ 4 (CYCLOPENTYLAMINO) 6 ETHOXY 1,3,5 TRIAZIN 2 YL]THIOMORPHOLINE 1,1 DIOXIDE; 4 [ 4 ETHOXY 6 ( 4 METHYLPIPERIDIN 1 YL) 1,3,5 TRIAZIN 2 YL]THIOMORPJOLINE 1,1 DIOXIDE; 4 [( 4 ADAMANTAN 1 YLAMINO) 6 ETHOXY 1,3,5 TRIAZIN 2 YL] THIOMORPHOLINE 1,1 DIOXIDE; 6 IODO 3 (4 METHOXYBENZOYL) 2 METHYL 1 (2 MORPHOLINOETHYL)INDOLE; ANDROGEN; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR AGONIST; DEXANABINOL; FLUORINE 18; N (ADAMANTAN 1 YL) 4 ETHOXY 6 ( 4 METHYLPIPERAZIN 1 YL) 1,3,5 TRIAZIN 2 AMINE; N (ADAMANTAN 1 YL) 4 ETHOXY 6 ( 4 METHYLPIPERAZIN 1 YL) 1,3,5 TRIAZINE 2 AMINE; N (ADAMANTAN 1 YL) 4 ETHOXY 6 (PIPERAZIN 1 YL) 1,3,5 TRIAZIN 2 AMINE; N CYCLOPENTYL 4 ETHOXY 6 ( 4 METHYLPIPERAZIN 1 YL) 1,3,5 TRIAZIN 2 AMINE; N CYCLOPENTYL 4 ETHOXY 6 (PIPERAZIN 1 YL) 1,3,5 TRIAZIN 2 AMINE; N CYCLOPENTYL 4 ETHOXY 6 MORPHOLINO 1,3,5 TRIAZIN 2 AMINE; N CYCLOPENTYL 4 ETHOXY 6 [ 4 ( 2 FLUORO 18 ETHYL)PIPERAZIN 1 YL] 1,3,5 TRIAZIN 2 AMINE; N [ADAMANTAN 1 YL] 4 ETHOXY 6 [ 4 ( 2 FLUOROETHYL)PIPERAZIN 1 YL] 1,3,5 TRIAZIN 2 AMINE; PIPERAZINE DERIVATIVE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG; WATER; ANTINEOPLASTIC AGENT; CANNABINOID RECEPTOR AGONIST; FLUORINE; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); OCTANOL;

ANIMAL EXPERIMENT; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG POTENCY; DRUG SOLUBILITY; DRUG STABILITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LNCAP CELL LINE; MALE; MELANOMA CELL; MELANOMA CELL LINE; NONHUMAN; OXIDATIVE STRESS; PIGMENT EPITHELIUM; POSITRON EMISSION TOMOGRAPHY; PROSTATE; RAT; AGONISTS; ANIMAL; CELL LINE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; METABOLISM; SOLUBILITY; SPRAGUE DAWLEY RAT; SYNTHESIS; TISSUE DISTRIBUTION; TUMOR CELL LINE;

1-OCTANOL; ANIMALS; ANTINEOPLASTIC AGENTS; CANNABINOID RECEPTOR AGONISTS; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; FLUORINE RADIOISOTOPES; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); HUMANS; MALE; RATS, SPRAGUE-DAWLEY; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; SOLUBILITY; TISSUE DISTRIBUTION; TRIAZINES; WATER;

EID: 84912544318     PISSN: 09280987     EISSN: 18790720     Source Type: Journal    
DOI: 10.1016/j.ejps.2014.11.003     Document Type: Article

References (34)

1. N. Aaltonen, J.R. Savinainen, C.R. Ribas, J. Rönkkö, A. Kuusisto, J. Korhonen, D. Navia-Paldanius, J. Häyrinen, P. Takabe, H. Käsnänen, T. Pantsar, T. Laitinen, M. Lehtonen, S. Pasonen-Seppänen, A. Poso, T. Nevalainen, and J.T. Laitinen Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase Chem. Biol. 20 3 2013 379 390
2. 11C]-NE40 in healthy subjects Mol. Imag. Biol. 15 4 2013 384 390
3. C. Blázquez, A. Carracedo, L. Barrado, P.J. Real, J.L. Fernández-Luna, G. Velasco, M. Malumbres, and M. Guzmán Cannabinoid receptors as novel targets for the treatment of melanoma FASEB J. 20 14 2006 2633 2635
4. M. Duncan, A. Mouihate, K. Mackie, C.M. Keenan, N.E. Buckley, J.S. Davison, K.D. Patel, Q.J. Pittman, and K.A. Sharkey Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats Am. J. Physiol. Gastrointest Liver Physiol. 295 1 2008 G78 G87
5. N. Evens, B. Bosier, B.J. Lavey, J.A. Kozlowski, P. Vermaelen, L. Baudemprez, R. Busson, D.M. Lambert, K. Van Laere, A.M. Verbruggen, and G.M. Bormans Labelling and biological evaluation of [(11)C]methoxy-Sch225336: a radioligand for the cannabinoid-type 2 receptor Nucl. Med. Biol. 35 7 2008 793 800
6. N. Evens, C. Vandeputte, G.G. Muccioli, D.M. Lambert, V. Baekelandt, A.M. Verbruggen, Z. Debyser, K. Van Laere, and G.M. Bormans Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging Bioorg. Med. Chem. 19 15 2011 4499 4505
7. N. Evens, C. Vandeputte, C. Coolen, P. Janssen, R. Sciot, V. Baekelandt, A.M. Verbruggen, Z. Debyser, K. Van Laere, and G.M. Bormans Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer Nucl. Med. Biol. 39 3 2012 389 399
8. M. Fujinaga, K. Kumata, K. Yanamoto, K. Kawamura, T. Yamasaki, J. Yui, A. Hatori, M. Ogawa, Y. Yoshida, N. Nengaki, J. Maeda, and M.R. Zhang Radiosynthesis of novel carbon-11-labeled triaryl ligands for cannabinoid-type 2 receptor Bioorg. Med. Chem. Lett. 20 5 2010 1565 1568
9. M. Gao, M. Wang, K.D. Miller, G.D. Hutchins, and Q.H. Zheng Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging Bioorg. Med. Chem. 18 6 2010 2099 2106
10. S. Han, J. Thatte, D.J. Buzard, and R.M. Jones Therapeutic utility of cannabinoid receptor type 2 (CB2) selective agonists J. Med. Chem. 56 21 2013 8224 8256
11. B. Herrera, A. Carracedo, M. Diez-Zaera, T. Gómez del Pulgar, M. Guzmán, and G. Velasco The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway Exp. Cell Res. 312 11 2006 2121 2131
12. L. Hortala, J. Arnaud, P. Roux, D. Oustric, L. Boulu, F. Oury-Donat, P. Avenet, T. Rooney, D. Alagille, O. Barret, G. Tamagnan, and F. Barth Synthesis and preliminary evaluation of a new fluorine-18 labelled triazine derivative for PET imaging of cannabinoid CB2 receptor Bioorg. Med. Chem. Lett. 24 1 2014 283 287
13. A.G. Horti, Y. Gao, H.T. Ravert, P. Finley, H. Valentine, D.F. Wong, C.J. Endres, A.V. Savonenko, and R.F. Dannals Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2) Bioorg. Med. Chem. 18 14 2010 5202 5207
14. W. Jia, V.L. Hegde, N.P. Singh, D. Sisco, S. Grant, M. Nagarkatti, and P.S. Nagarkatti Δ9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria Mol. Cancer Res. 4 8 2006 549 562
15. D.M. Lambert, and C.J. Fowler The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications J. Med. Chem. 48 16 2005 5059 5087
16. C. Lombard, M. Nagarkatti, and P.S. Nagarkatti Targeting cannabinoid receptors to treat leukemia: role of cross-talk between extrinsic and intrinsic pathways in Δ9-tetrahydrocannabinol (THC)-induced apoptosis of Jurkat cells Leuk Res. 29 8 2005 915 922
17. D. Lu, Z. Meng, G.A. Thakur, P. Fan, J. Steed, C.L. Tartal, D.P. Hurst, P.H. Reggio, J.R. Deschamps, D.A. Parrish, C. George, T.U. Järbe, R.J. Lamb, and A. Makriyannis Adamantyl cannabinoids: a novel class of cannabinergic ligands J. Med. Chem. 48 14 2005 4576 4585
18. L. Mu, D. Bieri, R. Slavik, K. Drandarov, A. Müller, S. Cermak, M. Weber, R. Schibli, S.D. Krämer, and S.M. Ametamey Radiolabeling and in vitro/in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoid type 2 receptor J. Neurochem. 126 5 2013 616 624
19. D.K. Nomura, J.Z. Long, S. Niessen, H.S. Hoover, S.W. Ng, and B.F. Cravatt Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis Cell 140 1 2010 49 61
20. P. Pacher, and G. Kunos Modulating the endocannabinoid system in human health and disease - successes and failures FEBS J. 280 9 2013 1918 1943
21. P. Pacher, and R. Mechoulam Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog. Lipid Res. 50 2 2011 193 211
22. P. Pacher, S. Bátkai, and G. Kunos The endocannabinoid system as an emerging target of pharmacotherapy Pharmacol. Rev. 58 3 2006 389 462
23. R.G. Pertwee Pharmacology of cannabinoid CB1 and CB2 receptors Pharmacol. Ther. 74 2 1997 129 180
24. G. Repetto, A. del Peso, and J.L. Zurita Neutral red uptake assay for the estimation of cell viability/cytotoxicity Nat. Protoc. 3 7 2008 1125 1131
25. S.A. Rieder, A. Chauhan, U. Singh, M. Nagarkatti, and P. Nagarkatti Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression Immunobiology 215 8 2010 598 605
26. T. Rühl, W. Deuther-Conrad, S. Fischer, R. Günther, L. Hennig, H. Krautscheid, and P. Brust Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation Org. Med. Chem. Lett. 2 1 2012 32
27. S. Sarfaraz, F. Afaq, V.M. Adhami, and H. Mukhtar Cannabinoid receptor as a novel target for the treatment of prostate cancer Cancer Res. 65 5 2005 1635 1641
28. J.R. Savinainen, S.M. Saario, R. Niemi, T. Järvinen, and J.T. Laitinen An optimized approach to study endocannabinoid signaling: evidence against constitutive activity of rat brain adenosine A1 and cannabinoid CB1 receptors Br. J. Pharmacol. 140 2003 1451 1459
29. J.R. Savinainen, T. Kokkola, O.M.H. Salo, A. Poso, T. Järvinen, and J.T. Laitinen Identification of WIN55212-3 as a competitive neutral antagonist of the human cannabinoid CB2 receptor Br. J. Pharmacol. 45 2005 636 645
30. 18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor Nucl. Med. Biol. 39 4 2012 593 600
31. Y. Wei, X. Wang, and L. Wang Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells Mol. Vis. 15 2009 1243 1251
32. D.R. Welch, J.E. Bisi, B.E. Miller, D. Conaway, E.A. Seftor, K.H. Yohem, L.B. Gilmore, R.E. Seftor, M. Nakajima, and M.J. Hendrix Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line Int. J. Cancer 47 1991 227 237
33. Yrjölä, S., Kalliokoski, T., Navia-Paldanius, D., Laitinen, T., Nevalainen, T., Poso, A., 2011. Ligand-based virtual screening for cannabinoid ligands. In: Poster session presented at: 21st Annual symposium of the International Cannabinoid Research Society 2011 July 5-10, St. Charles, IL, USA.
34. S. Yrjölä, T. Kalliokoski, T. Laitinen, A. Poso, T. Parkkari, and T. Nevalainen Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of 2,4,6-trisubstituted 1,3,5-triazines as CB2 agonists Eur. J. Pharm. Sci. 48 1-2 2013 9 20