The SAR studies of novel CB2 selective agonists, benzimidazolone derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 11, 2008, Pages 3310-3314

  Omura, Hirofumi ^a   Kawai, Makoto ^a   Shima, Akiko ^a   Iwata, Yasuhiro ^a   Ito, Fumitaka ^a   Masuda, Tsutomu ^a   Ohta, Atsuko ^a   Makita, Naoya ^a   Omoto, Kiyoyuki ^a   Sugimoto, Hiromi ^a   Kikuchi, Akira ^a   Iwata, Hiroshi ^a   Ando, Kazuo ^a  

^a PFIZER INC   (United States)

Author keywords

Benzimidazolone; Cannabinoid; CB2 agonist; Metabolic stability

Indexed keywords

BENZIMIDAZOLONE DERIVATIVE; CANNABINOID RECEPTOR AGONIST; QUINAZOLINONE DERIVATIVE;

ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZIMIDAZOLES; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; HUMANS; MOLECULAR STRUCTURE; RATS; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 44149096011     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.04.032     Document Type: Article

References (37)

1. Munro S., Thomas K.L., and Abu-Shaar M. Nature 365 (1993) 61
2. For general reviews of the cannabinoid, see. Pertwee R.G. Pharmacol. Ther. 74 (1997) 129
3. Pertwee R.G. Expert Opin. Invest. Drugs 9 (2000) 1553
4. Adam J., and Cowley P. Expert Opin. Ther. Patents 12 (2002) 1475
5. Goya P., and Jagerovic N. Expert Opin. Ther. Patents 10 (2000) 1529
6. Reggio P.H. Curr. Pharm. Des. 9 (2003) 1607
7. Di Carlo G., and Izzo A.A. Expert Opin. Invest. Drugs 12 (2003) 39
8. Herzog D.L. Expert Opin. Ther. Patents 14 (2004) 1435
9. Hanus L.O., and Mechoulam R. Cannabinoids Ther. (2005) 23
10. Huffman J.W., and Padgett L.W. Curr. Med. Chem. 12 (2005) 1395
11. Pavlopoulos S., Thakur G.A., Nikas S.P., and Makriyannis A. Curr. Pharm. Des. 12 (2006) 1751
12. Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., and Bonner T.I. Nature 346 (1990) 561
13. Huffman J.W. Curr. Pharm. Des. 6 (2000) 1323
14. Huffman J.W. Mini-Rev. Med. Chem. 5 (2005) 641
15. Raitio K.H., Salo O.M.H., Nevalainen T., Poso A., and Jarvinen T. Curr. Med. Chem. 12 (2005) 1217
16. Malan Jr. T.P., Ibrahim M.M., Deng H., Liu Q., Mata H.P., Vanderah T., Porreca F., and Makriyannis A. Pain 93 (2001) 239
17. Ibrahim M.M., Deng H., Zvonok A., Cockayne D.A., Kwan J., Mata H.P., Vanderah T.W., Lai J., Porreca F., Makriyannis A., and Malan Jr. T.P. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 10529
18. Makriyannis, A.; Deng, H. WO02/060447.
19. Hanus L., Breuer A., Tchilibon S., Shiloah S., Goldenberg D., Horowitz M., Pertwee R.G., Ross R.A., Mechoulam R., and Fride E. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 14228
20. Malan Jr. T.P., Ibrahim M.M., Lai J., Vanderah T.W., Makriyannis A., and Porreca F. Curr. Opin. Pharmacol. 3 (2003) 62
21. Cannabinoids for pain therapeutics, see. Di Marzo V., Bifulco M., and De Petrocellis L. Nat. Rev. Drug Discov. 3 (2004) 771
22. Huang S.M., and Walker J.M. Cannabinoids Ther. (2005) 149
23. Ben Amar M. J. Ethnopharmacol. 105 (2006) 1
24. Whiteside G.T., Lee G.P., and Valenzano K.J. Curr. Med. Chem. 14 (2007) 917
25. Compound 1:. D'Ambra T.E., Estep K.G., Bell M.R., Eissenstat M.A., Josef K.A., Ward S.J., Haycock D.A., Baizman E.R., Casiano F.M., Beglin N.C., Chippari S.M., Grego J.D., Kullnig R.K., and Daley G.T. J. Med. Chem. 35 (1992) 124
26. Compound 3:. Hynes Jr. J., Leftheris K., Wu H., Pandit C., Chen P., Norris D.J., Chen B.-C., Zhao R., Kiener P.A., Chen X., Turk L.A., Patil-Koota V., Gillooly K.M., Shuster D.J., and McIntyre K.W. Bioorg. Med. Chem. Lett. 12 (2002) 2399
27. Wrobleski S.T., Chen P., Hynes Jr. J., Lin S., Norris D.J., Pandit C.R., Spergel S., Wu H., Tokarski J.S., Chen X., Gillooly K.M., Kiener P.A., McIntyre K.W., Patil-koota V., Shuster D.J., Turk L.A., Yang G., and Leftheris K. J. Med. Chem. 46 (2003) 2110
28. Compound 4: Makriyannis, A.; Liu, Q. WO03/035005.
29. Toxicity of aniline was reported. see:. Famulok M., and Boche G. Angew. Chem., Int. Ed. Engl. 28 (1989) 468
30. Marques M.M., Mourato L.L.G., Amorim M.T., Santos M.A., Melchior Jr. W.B., and Beland F.A. Chem. Res. Toxicol. 10 (1997) 1266
31. Ando, K.; Kawai, M.; Masuda, T.; Omura, H. WO 2006/097808.
32. Nassar A.-E.F., Kamel A.M., and Clarimont C. Drug Discov. Today 9 (2004) 1020
33. Brown M.F., Bahnck K.B., Blumberg L.C., Brissette W.H., Burrell S.A., Driscoll J.P., Fedeles F., Fisher M.B., Foti R.S., Gladue R.P., Guzman-Martinez A., Hayward M.M., Lira P.D., Lillie B.M., Lu Y., Lundquist G.D., McElroy E.B., McGlynn M.A., Paradis T.J., Poss C.S., Roache J.H., Shavnya A., Shepard R.M., Trevena K.A., and Tylaska L.A. Bioorg. Med. Chem. Lett. 17 (2007) 3109
34. Similar trends were reported by other research groups. see: Refs. 2e,10b.
35. The introduction of a methyl group at 4-position on the benzimidazolone ring of compound 34 enhanced its CB2 binding activity up to 5 nM from 338 nM. Similar study of substituent effect was reported. see: Ref. 10a.
36. Spectrum data of compound 39 were described in Ref. 13.
37. See Ref. 13 for the assay protocol.