Novel pyrazole derivatives as neutral CB1 antagonists with significant activity towards food intake

European Journal of Medicinal Chemistry

Volumn 62, Issue , 2013, Pages 256-269

  Manca, Ilaria ^a   Mastinu, Andrea ^b   Olimpieri, Francesca ^c   Falzoi, Matteo ^d,e   Sani, Monica ^d,f   Ruiu, Stefania ^b   Loriga, Giovanni ^b   Volonterio, Alessandro ^c,f   Tambaro, Simone ^a   Bottazzi, Mirko Emilio Heiner ^b   Zanda, Matteo ^f,g   Pinna, Gérard Aimè ^h   Lazzari, Paolo ^a,d,h  

^a Neuroscienze PharmaNess Scarl   (Italy)

^b INSTITUTE OF TRANSLATIONAL PHARMACOLOGY   (Italy)

^c Dipartimento di Chimica Materiali e Ingegneria Chimica Giulio Natta   (Italy)

^d Edificio 3 ^*  (Italy)

^e Dipartimento di Scienze della Vita e dell'Ambiente   (Italy)

^f CNR   (Italy)

^g UNIVERSITY OF ABERDEEN   (United Kingdom)

^h UNIVERSITY OF SASSARI   (Italy)

Author keywords

Cannabinoids; CB1 receptor; Fluorinated ligands; Food intake

Indexed keywords

5 (4 CHLOROPHENYL) 1 (2,4 DICHLOROPHENYL) 3 (2 CYCLOHEXYL 1 HYDROXYETHYL) 4 METHYL 1H PYRAZOLE; 5 (4 CHLOROPHENYL) 1 (2,4 DICHLOROPHENYL) 3 [2 CYCLOHEXYL 1 FLUOROVINYL] 4 METHYL 1H PYRAZOLE; CANNABINOID 1 RECEPTOR ANTAGONIST; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG SCREENING; ENANTIOMER; FOOD INTAKE; IN VIVO STUDY; MOUSE; NONHUMAN;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; EATING; MALE; MICE; MOLECULAR STRUCTURE; PYRAZOLES; RECEPTOR, CANNABINOID, CB1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84873033581     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.12.056     Document Type: Article

References (66)

1. J. Antel, P.C. Gregory, and U. Nordheim CB1 cannabinoid receptor antagonists for treatment of obesity and prevention of comorbid metabolic disorders J. Med. Chem. 49 2006 4008 4016
2. C.C. Felder, K.E. Joyce, E.M. Briley, M. Glass, K.P. Mackie, K.J. Fahey, G.J. Cullinan, D.C. Hunden, D.W. Johnson, M.O. Chaney, G.A. Koppel, and M. Brownstein LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation J. Pharmacol. Exp. Ther. 284 1998 291 297
3. S.Y. Kang, S.H. Lee, H.J. Seo, M.E. Jung, K. Ahn, J. Kim, and J. Lee Tetrazole-biarylpyrazole derivatives as cannabinoid CB1 receptor antagonists Bioorg. Med. Chem. Lett. 18 2008 2385 2389
4. J.H.M. Lange, H.K.A.C. Coolen, H.H. van Stuivenberg, J.A.R. Dijksman, A.H.J. Herremans, E. Ronken, H.G. Keizer, K. Tipker, A.C. McCreary, W. Veerman, H.C. Wals, B. Stork, P.C. Verveer, A.P. den Hartog, N.M.J. de Jong, T.J.P. Adolfs, J. Hoogendoorn, and C.G. Kruse Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB1 cannabinoid receptor antagonists J. Med. Chem. 47 2004 627 643
5. J.H.M. Lange, and C.G. Kruse Keynote review: medicinal chemistry strategies to CB1 cannabinoid receptor antagonists Drug Discov. Today 10 2005 693 702
6. J.H.M. Lange, H.H. van Stuivenberg, W. Veerman, H.C. Wals, B. Stork, H.K.A.C. Coolen, A.C. McCreary, T.J.P. Adolfs, and C.G. Kruse Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity Bioorg. Med. Chem. Lett. 15 2005 4794 4798
7. M. Rinaldi-Carmona, F. Barth, M. Héaulme, D. Shire, B. Calandra, C. Congy, S. Martinez, J. Maruani, G. Néliat, D. Caput, P. Ferrara, P. Soubrié, J.C. Brelère, and G. Le Fur SR141716A, a potent and selective antagonist of the brain cannabinoid receptor FEBS Lett. 350 1994 240 244
8. H.H. Seltzman Recent CB1 cannabinoid receptor antagonists and inverse agonists Drug Dev. Res. 70 2009 601 615
9. K.S. Sink, V.K. Vemuri, J. Wood, A. Makriyannis, and J.D. Salamone Oral bioavailability of the novel cannabinoid CB1 antagonist AM6527: effects on food-reinforced behavior and comparisons with AM4113 Pharmacol. Biochem. Behav. 91 2009 303 306
10. H. Wang, R.A. Duffy, G.C. Boykow, S. Chackalamannil, and V.S. Madison Identification of novel cannabinoid CB1 receptor antagonists by using virtual screening with a pharmacophore model J. Med. Chem. 51 2008 2439 2446
11. P. Lazzari, A. Pau, S. Tambaro, B. Asproni, S. Ruiu, G. Pinna, A. Mastinu, M.M. Curzu, R. Reali, M.E.H. Bottazzi, G.A. Pinna, and G. Murineddu Cent. Nerv. Syst. Agents Med. Chem. 12 2012 254 276
12. A.C. Howlett, F. Barth, T.I. Bonner, G. Cabral, P. Casellas, W.A. Devane, C.C. Felder, M. Herkenham, K. Mackie, B.R. Martin, R. Mechoulam, and R.G. Pertwee International union of pharmacology. XXVII. Classification of cannabinoid receptors Pharmacol. Rev. 54 2002 161 202
13. R.G. Pertwee Cannabinoid receptors and pain Prog. Neurobiol. 63 2001 569 611
14. A. Porcella, C. Maxia, G.L. Gessa, and L. Pani The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies Eur. J. Neurosci. 13 2001 409 412
15. T.W. Klein Cannabinoid-based drugs as anti-inflammatory therapeutics Nat. Rev. Immunol. 5 2005 400 411
16. J.C. Blanchard, F. Menard, Use of Central Cannabinoid Receptor Antagonist for Preparing Medicines Designed to Facilitate Smoking Cessation, US Patent 6,930,122, Sanofi-Aventis, Paris (FR), 2005.
17. M.A.M. Carai, G. Colombo, and G.L. Gessa Rimonabant: the first therapeutically relevant cannabinoid antagonist Life Sci. 77 2005 2339 2350
18. K. Jordan, C. Kasper, and H.J. Schmoll Chemotherapy-induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment Eur. J. Cancer 41 2005 199 205
19. M.D. Van Sickle, L.D. Oland, W. Ho, C.J. Hillard, K. Mackie, J.S. Davison, and K.A. Sharkey Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret Gastroenterology 121 2001 767 774
20. J. Fernández-Ruiz The endocannabinoid system as a target for the treatment of motor dysfunction Br. J. Pharmacol. 156 2009 1029 1040
21. J.E. Kelsey, O. Harris, and J. Cassin The CB1 antagonist rimonabant is adjunctively therapeutic as well as monotherapeutic in an animal model of Parkinson's disease Behav. Brain Res. 203 2009 304 307
22. C. Blazquez, A. Carracedo, L. Barrado, P.J. Real, J.L. Fernandez-Luna, G. Velasco, M. Malumbres, and M. Guzman Cannabinoid receptors as novel targets for the treatment of melanoma FASEB J. 20 2006 E2199 E2208
23. S.Y. Lim, S.M. Davidson, D.M. Yellon, and C.C.T. Smith The cannabinoid CB1 receptor antagonist, rimonabant, protects against acute myocardial infarction Basic Res. Cardiol. 104 2009 781 792
24. M.A. Huestis, S.J. Boyd, S.J. Heishman, K.L. Preston, D. Bonnet, G. Le Fur, and D.A. Gorelick Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users Psychopharmacology 194 2007 505 515
25. B. Le Foll, and S.R. Goldberg Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence J. Pharmacol. Exp. Ther. 312 2005 875 883
26. K. Mackie Cannabinoid receptors as therapeutic targets Annu. Rev. Pharmacol. Toxicol. 46 2006 101 122
27. F. Teixeira-Clerc, B. Julien, P. Grenard, J.T. Van Nhieu, V. Deveaux, L. Li, V. Serriere-Lanneau, C. Ledent, A. Mallat, and S. Lotersztajn CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis Nat. Med. 12 2006 671 676
28. M. Gary-Bobo, G. Elachouri, J.F. Gallas, P. Janiak, P. Marini, C. Ravinet-Trillou, M. Chabbert, N. Cruccioli, C. Pfersdorff, C. Roque, M. Arnone, T. Croci, P. Soubrie, F. Oury-Donat, J.P. Maffrand, B. Scatton, F. Lacheretz, G. Le Fur, J.M. Herbert, and M. Bensaid Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats Hepatology 46 2007 122 129
29. S. Succu, M.S. Mascia, F. Sanna, T. Melis, A. Argiolas, and M.R. Melis The cannabinoid CB1 receptor antagonist SR 141716A induces penile erection by increasing extra-cellular glutamic acid in the paraventricular nucleus of male rats Behav. Brain Res. 169 2006 274 281
30. J.P. Després, A. Golay, and L. Sjöström Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia N. Engl. J. Med. 353 2005 2121 2134
31. A.J. Scheen, N. Finer, P. Hollander, M.D. Jensen, and L.F. Van Gaal Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study Lancet 368 2006 1660 1672
32. D. Jones End of the line for cannabinoid receptor 1 as an anti-obesity target? Nat. Rev. Drug Discov. 7 2008 961 962
33. R.G. Pertwee Emerging strategies for exploiting cannabinoid receptor agonists as medicines Br. J. Pharmacol. 156 2009 397 411
34. F. Akbas, C. Gasteyger, A. Sjödin, A. Astrup, and T.M. Larsen A critical review of the cannabinoid receptor as a drug target for obesity management Obes. Rev. 10 2009 58 67
35. T.L. Horvath The unfolding cannabinoid story on energy homeostasis: central or peripheral site of action? Int. J. Obes. 30 2006 S30 S32
36. J. LoVerme, A. Duranti, A. Tontini, G. Spadoni, M. Mor, S. Rivara, N. Stella, C. Xu, G. Tarzia, and D. Piomelli Synthesis and characterization of a peripherally restricted CB1 cannabinoid antagonist, URB447, that reduces feeding and body-weight gain in mice Bioorg. Med. Chem. Lett. 19 2009 639 643
37. J.M. Receveur, A. Murray, J.M. Linget, P.K. Nørregaard, M. Cooper, E. Bjurling, P.A. Nielsen, and T. Högberg Conversion of 4-cyanomethyl-pyrazole-3-carboxamides into CB1 antagonists with lowered propensity to pass the blood-brain-barrier Bioorg. Med. Chem. Lett. 20 2010 453 457
38. K.S. Sink, P.J. McLaughlin, J.A.T. Wood, C. Brown, P. Fan, V.K. Vemuri, Y. Pang, T. Olzewska, G.A. Thakur, A. Makriyannis, L.A. Parker, and J.D. Salamone The novel cannabinoid CB1 receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats Neuropsychopharmacology 33 2008 946 955
39. D. Hurst, U. Umejiego, D. Lynch, H. Seltzman, S. Hyatt, M. Roche, S. McAllister, D. Fleischer, A. Kapur, and M. Abood Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: importance of the C-3 carboxamide oxygen/lysine3. 28(192) interaction J. Med. Chem. 49 2006 5969 5987
40. S.D. McAllister, G. Rizvi, S. Anavi-Goffer, D.P. Hurst, J. Barnett-Norris, D.L. Lynch, P.H. Reggio, and M.E. Abood An aromatic microdomain at the cannabinoid CB1 receptor constitutes an agonist/inverse agonist binding region J. Med. Chem. 46 2003 5139 5152
41. S.D. McAllister, Q. Tao, J. Barnett-Norris, K. Buehner, D.P. Hurst, F. Guarnieri, P.H. Reggio, K.W. Nowell Harmon, G.A. Cabral, and M.E. Abood A critical role for a tyrosine residue in the cannabinoid receptors for ligand recognition Biochem. Pharmacol. 63 2002 2121 2136
42. D.P. Hurst, D.L. Lynch, J. Barnett-Norris, S.M. Hyatt, H.H. Seltzman, M. Zhong, Z.H. Song, J. Nie, D. Lewis, and P.H. Reggio N-(Piperidin-1-yl)-5-(4- chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor Mol. Pharmacol. 62 2002 1274 1287
43. I.R. Greig, R.A. Ross, R.G. Pertwee, 1,5-Diarylpyrazoles as a Cannabinoid Receptor Neutral Antagonists Useful as Therapeutic Agents, US Patent 20100022611A1, University of Aberdeen, Aberdeenshire (GB), 2010.
44. R.G. Pertwee Inverse agonism and neutral antagonism at cannabinoid CB1 receptors Life Sci. 76 2005 1307 1324
45. R.G. Pertwee The pharmacology of cannabinoid receptors and their ligands: an overview Int. J. Obes. 30 2006 S13 S18
46. M. Sani, A. Volonterio, and M. Zanda The trifluoroethylamine function as peptide bond replacement ChemMedChem 2 2007 1693 1700
47. K.V. Kumar, J. Reddy, S.K. Suthrapu, C.P. Rao, P.P. Reddy, A. Bhattacharya, and R. Bandichhor Synthesis of rimonabant regioisomer Monatsh. Chem. 139 2008 1091 1093
48. C.H. Wu, M.S. Hung, J.S. Song, T.K. Yeh, M.C. Chou, C.M. Chu, J.J. Jan, M.T. Hsieh, S.L. Tseng, C.P. Chang, W.P. Hsieh, Y. Lin, Y.N. Yeh, W.L. Chung, C.W. Kuo, C.Y. Lin, H.S. Shy, Y.S. Chao, and K.S. Shia Discovery of 2-[5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5, 5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an active metabolite. A novel, potent and selective cannabinoid-1 Receptor inverse agonist with high antiobesity efficacy in DIO mice J. Med. Chem. 52 2009 4496 4510
49. G.K. Prakash, and A.K. Yudin Perfluoroalkylation with organosilicon reagents Chem. Rev. 97 1997 757 786
50. A.J. Mancuso, and D. Swern Activated dimethyl sulfoxide: useful reagents for synthesis Synthesis 1981 1981 165 185
51. K. Omura, and D. Swern Oxidation of alcohols by "activated" dimethyl sulfoxide. A preparative, steric and mechanistic study Tetrahedron 34 1978 1651 1660
52. T.T. Tidwell Oxidation of alcohols to carbonyl compounds via alkoxysulfonium ylides: the Moffatt, Swern, and related oxidations Org. React. 39 1990 297 572
53. T.T. Tidwell Oxidation of alcohols by activated dimethyl sulfoxide and related reactions: an update Synthesis 10 1990 857 870
54. S. Fries, J. Pytkowicz, and T. Brigaud Highly diastereoselective addition of organometallic reagents to a trifluoroacetaldehyde hydrazone derived from (R)-N-benzylphenylglycinol Tetrahedron Lett. 46 2005 4761 4764
55. W.H. Pirkle, and J.R. Hauske Design of chiral derivatizing agents for the chromatographic resolution of optical isomers. Asymmetric synthesis of some chiral fluoroalkylated amines J. Org. Chem. 42 1977 2436 2439
56. N.I. Ghali, D.L. Venton, S.C. Hung, and G.C. Le Breton High-yielding synthesis of monoalkylhydrazines J. Org. Chem. 46 1981 5413 5414
57. P.L. Wu, S.Y. Peng, and J. Magrath 1-Acyl-2-alkylhydrazines by the reduction of acylhydrazones Synthesis 4 1995 435 438
58. D. Perdicchia, E. Licandro, S. Maiorana, C. Baldoli, and C. Giannini A new 'one-pot' synthesis of hydrazides by reduction of hydrazones Tetrahedron 59 2003 7733 7742
59. G. Murineddu, P. Lazzari, S. Ruiu, A. Sanna, G. Loriga, I. Manca, M. Falzoi, C. Dessì, M.M. Curzu, G. Chelucci, L. Pani, and G.A. Pinna Tricyclic pyrazoles. 4. Synthesis and biological evaluation of analogues of the robust and selective CB2 cannabinoid ligand 1-(2′,4′-dichlorophenyl) -6-methyl-N-piperidin-1-yl-1,4-dihydroindeno [1,2-c] pyrazole-3-carboxamide J. Med. Chem. 49 2006 7502 7512
60. i) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction Biochem. Pharmacol. 22 1973 3099 3108
61. M.I. Davis, J. Ronesi, and D.M. Lovinger A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells J. Biol. Chem. 278 2003 48973 48980
62. R.G. Pertwee, G. Griffin, J.A.H. Lainton, and J.W. Huffman Pharmacological characterization of three novel cannabinoid receptor agonists in the mouse isolated vas deferens Eur. J. Pharmacol. 284 1995 241 247
63. V. Di Marzo, S.K. Goparaju, L. Wang, J. Liu, S. Batkal, Z. Járai, F. Fezza, G.I. Miura, R.D. Palmiter, and T. Sugiura Leptin-regulated endocannabinoids are involved in maintaining food intake Nature 2001 822 824
64. 3)]-retro-thiorphan Tetrahedron Lett. 48 2007 589 593
65. E. Schlicker, and M. Kathmann Modulation of transmitter release via presynaptic cannabinoid receptors Trends Pharmacol. Sci. 22 2001 565 572
66. S. Ruiu, G.A. Pinna, G. Marchese, J.M. Mussinu, P. Saba, S. Tambaro, P. Casti, R. Vargiu, and L. Pani Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor J. Pharmacol. Exp. Ther. 306 2003 363 370