Bioisosteric replacements of the pyrazole moiety of rimonabant: Synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists

Journal of Medicinal Chemistry

Volumn 48, Issue 6, 2005, Pages 1823-1838

  Lange, Jos H M ^a   Van Stuivenberg, Herman H ^a   Coolen, Hein K A C ^a   Adolfs, Tiny J P ^a   McCreary, Andrew C ^a   Keizer, Hiskias G ^a   Wals, Henri C ^a   Veerman, Willem ^a   Borst, Alice J M ^a   De Looff, Wouter ^a   Verveer, Peter C ^a   Kruse, Chris G ^a  

^a Solvay Pharmaceuticals Inc   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 CHLOROPHENYL) 2 (2,4 DICHLOROPHENYL) 5 METHYL N (PIPERIDIN 1 YL) 1H IMIDAZOLE 4 CARBOXAMIDE; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; IMIDAZOLE DERIVATIVE; PYRAZOLE; PYRAZOLE DERIVATIVE; RIMONABANT; THIAZOLE DERIVATIVE; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CHEMICAL STRUCTURE; CONFORMATION; DRUG SELECTIVITY; DRUG SYNTHESIS; HYDROGEN BOND; HYPOTENSION; HYPOTHERMIA; IN VITRO STUDY; MOLECULAR MODEL; NONHUMAN; POLYMERIZATION; RECEPTOR BINDING; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ADMINISTRATION, ORAL; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; CYCLOHEXANOLS; HYPOTENSION; HYPOTHERMIA; IMIDAZOLES; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PIPERIDINES; PYRAZOLES; RADIOLIGAND ASSAY; RATS; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TRIAZOLES;

EID: 20144379406     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040843r     Document Type: Article

References (57)

1. (a) Mechoulam, R.; Feigenbaum, J. J. Towards cannabinoid drugs. Prog. Med. Chem. 1987, 24, 159-207.
2. (b) Mechoulam, R.; Hanus, L.; Fride, I. Towards cannabinoid drugs - revisited. Prog. Med. Chem. 1998, 35, 199-243.
3. Matsuda, L. A.; Lolait, S. J.; Brownstein, B. J.; Young, A. C.; Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990, 356, 561-564.
4. Munro, S.; Thomas, K. L.; Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993, 365, 61-62.
5. (a) Wilson, R.; Nicoll, R. A. Endocannabinoid signaling in the brain. Science 2002, 296, 678-682.
6. (b) Palmer, S. L.; Thakur, G. A.; Makriyannis, A. Cannabinergic ligands. Chem. Phys. Lipids 2002, 121, 3-19.
7. (c) Razdan, R. K.; Mahadevan, A. Recent advances in the synthesis of endocannabinoid related ligands. Chem. Phys. Lipids 2002, 121, 21-33.
8. (d) De Petrocellis, L.; Cascio, M. G.; Di Marzo, V. The endocannabinoid system: A general view and latest additions. Br. J. Pharmacol. 2004, 141, 765-774.
9. (a) Breivogel, C. S.; Griffin, G.; Di Marzo, V.; Martin, B. R. Evidence for a new G protein-Coupled Cannabinoid receptor in mouse brain. Mol. Pharmacol. 2001, 60, 155-163.
10. (b) Wiley, J. L.; Martin, B. R. Cannabinoid pharmacology; Implications for additional cannabinoid receptor subtypes. Chem. Phys. Lipids 2002, 121, 57-63.
11. Herkenham, M. Localisation of cannabinoid receptors in brain and periphery. In Cannabinoid Receptors; Pertwee R. G., Ed.; Academic Press: New York, 1995; pp 145-166.
12. (a) Robson, P. Therapeutic aspects of cannabis and cannabinoids. Br. J. Psychiatry 2001, 178, 107-115.
13. (b) Croxford, J. L. Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 2003, 17, 179-202.
14. (c) Glass, M. The role of cannabinoids in neurodegenerative diseases. Progr. Neuro-Psychopharmacol., Biol. Psychiat. 2001, 25, 743-765.
15. (d) Consroe, P. Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol. Disease 1998, 5, 534-551.
16. (e) Drysdale, A. J.; Platt, B. Cannabinoids; Mechanisms and therapeutic applications in the CNS. Curr. Med. Chem. 2003, 10, 2719-2732.
17. Adam, J.; Cowley, P. Recent advances in the cannabinoids. Expert Opin. Ther. Pat. 2002, 12, 1475-1489.
18. Pertwee, R. G. Neuropharmacology and therapeutic potential of cannabinoids. Addiction Biol. 2000, 5, 37-46.
19. Gomez, R.; Navarro, M.; Ferrer, B.; Trigo, J. M.; Bilbao, A.; Del Arco, I.; Cippitelli, A.; Nava, F.; Piomelli, D.; De Fonseca, F. R. A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J. Neurosci. 2002, 22, 9612-9617.
20. Hall, W. Cannabis and psychosis. Drug Alcohol Rev. 1998, 17, 433-444.
21. Hungund, B. L.; Basavarajappa, B. S.; Vadasz, C.; Kunos, G.; de Fonseca, F. R.; Colombo, G.; Serra, S.; Parsons, L.; Koob, G. F. Ethanol, endocannabinoids, and the cannabinoidergic signaling system. Alcohol Clin. Exp. Res. 2002, 26, 565-574.
22. Pertwee, R. G. Cannabinoids and the gastrointestinal tract. Gut 2001, 48, 859-867.
23. (a) Palmer, S. L.; Thakur, G. A.; Makriyannis, A. Cannabinergic ligands. Chem. Phys. Lipids 2002, 121, 3-19.
24. (b) Reggio, P. H. Pharmacophores for ligand recognition and activation/inactivation of the cannabinoid receptors. Curr. Pharm. Des. 2003, 9, 1607-1633.
25. 1 cannabinoid receptor antagonists. Curr. Opin. Drug Discovery Dev. 2004, 7, 498-506.
26. 1 cannabinoid receptor antagonists. J. Med. Chem. 2004, 47, 627-643.
27. Lan, R.; Liu, Q.; Fan, P.; Lin, S.; Fernando, S. R.; McCallion, D.; Pertwee, R.; Makriyannis, A. Structure - activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem. 1999, 42, 769-776.
28. Nakamura-Palacios, E. M.; Moerschbaecher, J. M.; Barker, L. A. The pharmacology of SR 141716A: A review. CNS Drug Rev. 1999, 5, 43-58.
29. 1 receptor antagonist N-(piperidinyl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). J. Med. Chem. 2002, 45, 2708-2719.
30. 1 cannabinoid receptor. Biochem. Pharmacol. 2000, 60, 1315-1323.
31. 18F] SR 144385: A selective radioligand for positron emission tomographic studies of brain cannabinoid receptors. J. Labelled Compds. Radiopharm. 1999, 42, 589-596.
32. Katoch-Rouse, R.; Pavlova, O. A.; Caulder, T. Hoffman, A. F.; Mukhin, A. G.; Horti, A. G. Synthesis, structure - activity relationship, and evaluation of SR 141716 analogues: Development of central cannabinoid receptor ligands with lower lipophilicity. J. Med. Chem. 2003, 46, 642-645.
33. (a) Thornber, C. W. Isosterism and molecular modification in drug design. Chem. Soc. Rev. 1979, 8, 563-580.
34. (b) Chen, X.; Wang, W. The use of bioisosteric groups in lead optimization. In Annual Reports in Medicinal Chemistry; Doherty, A. M., Ed.; Elsevier Academic Press: Amsterdam, 2003; Vol. 38, pp 333-346.
35. Tsuji, K.; Nakamura, K.; Konishi, N.; Tojo, T.; Ochi, T.; Senoh, H.; Matsuo, M. Studies on antiinflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives. Chem. Pharm. Bull. 1997, 45, 987-995.
36. Kudo, N.; Furuta, S.; Taniguchi, M.; Endo, T.; Sato, K. Synthesis and herbicidal activity of 1,5-diarylpyrazole derivatives. Chem. Pharm. Bull. 1999, 47, 857-868.
37. Lipinski, C. A. Bioisosterism in drug design. In Annual Reports in Medicinal Chemistry; Bailey, D. M. Ed.; Academic Press: New York, 1986; Vol. 21, pp 283-291.
38. Tanaka, A.; Sakai, H.; Motoyama, Y.; Ishikawa, T.; Takasugi, H. Antiplatelet agents based on cyclooxygenase inhibition without ulcerogenesis. Evaluation and synthesis of 4,5-bis(4-methoxyphenyl)-2-substituted-thiazoles. J. Med. Chem. 1994, 37, 1189-1199.
39. Khanna, I. K.; Yu, Y.; Huff, R. M.; Weier, R. M.; Xu, X.; Koszyk, F. J.; Collins, P. W.; Cogburn, J. N.; Isakson, P. C.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Yuan, J.; Yang, D.; Zhang, Y. Y. Selective cyclooxygenase-2 inhibitors: Heteroaryl modified 1,2-diarylimidazoles are potent, orally active antiinflammatory agents. J. Med. Chem. 2000, 43, 3168-3185.
40. (a) Seifert, P.; Vogel, E.; Rossi, A.; Schinz, H. Einige Reaktionen an Derivaten von α-Ketosäuren und α-Ketosäureestern. Helv. Chim. Acta 1950, 33, 725-736.
41. (b) Plouvier, B.; Bailly, C.; Houssin, R.; Henichart, J.-P. Synthesis of two new thiazole-containing oligopeptides as potential DNA minor groove binding analogues of netropsin. Heterocycles 1991, 32, 693-701.
42. Levin, J. I.; Turos, E.; Weinreb, S. M. An alternative procedure for the aluminum-mediated conversion of esters to amides. Synth. Commun. 1982, 12, 989-993.
43. Snieckus, V. Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics. Chem. Rev. 1990, 90, 879-933.
44. Gerard, C. M.; Mollereau, C.; Vassart, G.; Parmentier M. Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem. J. 1991, 279, 129-134.
45. Showalter, V. M.; Compton, D. R.; Martin, B. R.; Abood, M. E. Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): Identification of cannabinoid receptor subtype selective ligands. J. Pharmacol. Exp. Ther. 1996, 278, 989-999.
46. Bayewitch, M.; Rhee, R. H.; Avidorreis, T.; Breuer, A.; Mechoulam, R.; Vogel, Z. (-)-Delta(9)-Tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase. J. Biol. Chem. 1996, 271, 9902-9905.
47. 1 receptor antagonists related to SR141716. Bioorg. Med. Chem. Lett. 2004, 14, 1151-1154.
48. Wagner, J. A.; Jarai, Z.; Batkai, S.; Kunos, G. Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB1 receptors. Eur. J. Pharmacol. 2001, 423, 203-210.
49. Rawls, S. M.; Cabassa, J.; Geller, E. B.; Adler, M. W. CB1 receptors in the preoptic anterior hypothalamus regulate WIN 55212-2 [(4,5-dihydro-2-methyl- 4-(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij] quinolin-6-one]-induced hypothermia. J. Pharmacol. Exp. Ther. 2002, 301, 963-968.
50. Hurst, D. P.; Lynch, D. L.; Barnett-Norris, J.; Hyatt, S. M.; Seltzman, H. H.; Zhong, M.; Song, Z.-H.; Nie, J.; Lewis, D.; Reggio, P. H. 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. 2002, 62, 1274-1287.
51. An alternative denotation is proposed since the common cis/ trans definition is not consistent in all the heterocyclic cores.
52. 1 receptor constitutes an agonist/inverse agonist binding region. J. Med. Chem. 2003, 46, 5139-5152.
53. Kelder, J.; Grootenhuis, P. D. J.; Bayada, D. M.; Delbressine, L. P. C.; Ploemen, J.-P. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm. Res. 1999, 16, 1514-1519.
54. Lin, J. H. How significant is the role of P-glycoprotein in drug absorption and brain uptake? Drugs Today 2004, 40, 5-22.
55. Ogata, M.; Matsumoto, H.; Takahashi, K.; Shimizu, S.; Kida, S.; Murabayashi, A.; Shiro, M.; Tawara, K. Synthesis and oral antifungal activity of novel azolylpropanolones and related compounds. J. Med. Chem. 1987, 30, 1054-1068.
56. Takahashi, K.; Shimizu, S.; Ogata, M. A convenient synthesis of 1H-1,2,4-triazol-1-yl-propan-3-one derivatives by modified Mannich reaction. Synth. Commun. 1987, 17, 809-815.
57. Tripos Inc., St. Louis, MO 63144.