Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 9, 2010, Pages 2770-2775

  Lange, Jos H M ^a   van der Neut, Martina A W ^a   Borst, Alice J M ^a   Yildirim, Mahmut ^a   van Stuivenberg, Herman H ^a   van Vliet, Bernard J ^a   Kruse, Chris G ^a  

^a Solvay Pharmaceuticals Inc   (Netherlands)

Author keywords

Cannabinoid CB1 receptor; Lipophilicity; Metasite; P Glycoprotein; Polar surface area; Rimonabant; Site of metabolism prediction; Subtype selectivity

Indexed keywords

AMIDE; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR ANTAGONIST; CANNABINOID RECEPTOR ANTAGONIST; GLYCOPROTEIN P; IMIDAZOLE DERIVATIVE; RIMONABANT; UNCLASSIFIED DRUG; 4 IMIDAZOLECARBOXAMIDE; 5 AMINO 4 IMIDAZOLECARBOXAMIDE; DRUG DERIVATIVE; IMIDAZOLE-4-CARBOXAMIDE; SULFONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG POTENCY; DRUG SYNTHESIS; DRUG TRANSPORT; HYPOTENSION; MOLECULAR PROBE; MOUSE; NONHUMAN; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; ANIMAL; CHEMISTRY; DISEASE MODEL; DRUG ANTAGONISM; INVERSE AGONISM; METABOLISM; ORAL DRUG ADMINISTRATION; RAT; SYNTHESIS;

RODENTIA;

ADMINISTRATION, ORAL; AMINOIMIDAZOLE CARBOXAMIDE; ANIMALS; DISEASE MODELS, ANIMAL; DRUG INVERSE AGONISM; HYPOTENSION; IMIDAZOLES; MICE; RATS; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 77950949471     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.03.068     Document Type: Article

References (47)

1. Lambert D.M., and Fowler M. J. Med. Chem. 48 (2005) 5059
2. van Gaal L.F., Rissanen A.M., Scheen A.J., Ziegler O., and Roessner S. Lancet 365 (2005) 1389
3. Lange J.H.M., and Kruse C.G. Chem. Rec. 8 (2008) 156
4. De Bruin, N. M. W. J.; Prickaerts, J.; Lange, J. H. M.; Akkerman, S.; Andriambeloson, E.; de Haan, M.; Wijnen, J.; van Drimmelen, M.; Hissink, E.; Heijink, L.; Kruse, C. G. Neurobiol. Learn. Memory, in press. doi:10.1016/j.nlm.2010.01.010.
5. Jones D. Nat. Rev. Drug Discovery 7 (2008) 961
6. Lan R., Liu Q., Fan P., Lin S., Fernando S.R., McCallion D., Pertwee R., and Makriyannis A. J. Med. Chem. 42 (1999) 769
7. Griffith D.A., Hadcock J.R., Black S.C., Iredale P.A., Carpino P.A., DaSilva-Jardine P., Day R., DiBrino J., Dow R.L., Landis M.S., O'Connor R.E., and Scott D.O. J. Med. Chem. 52 (2009) 234
8. Lin L.S., Lanza T.J., Jewell J.P., Liu P., Shah S.K., Qi H., Tong X., Wang J., Xu S.S., Fong T.M., Shen C.-P., Lao J., Xiao J.C., Shearman L.P., Stribling D.S., Rosko K., Strack A., Marsh D.J., Feng Y., Kumar S., Samuel K., Yin W., van der Ploeg L.H.T., Goulet M.T., and Hagmann W.K. J. Med. Chem. 49 (2006) 7584
9. Lange J.H.M., Coolen H.K.A.C., van Stuivenberg H.H., Dijksman J.A.R., Herremans A.H.J., Ronken E., Keizer H.G., Tipker K., McCreary A.C., Veerman W., Wals H.C., Stork B., Verveer P.C., den Hartog A.P., de Jong N.M.J., Adolfs T.J.P., Hoogendoorn J., and Kruse C.G. J. Med. Chem. 47 (2004) 627
10. Lange J.H.M., van Stuivenberg H.H., Veerman W., Wals H.C., Stork B., Coolen H.K.A.C., McCreary A.C., Adolfs T.J.P., and Kruse C.G. Bioorg. Med. Chem. Lett. 15 (2005) 4794
11. Bifulco M., and Pisanti S. Nat. Rev. Drug Discovery 8 (2009) 594
12. Le Foll B., Gorelick D.A., and Goldberg S.R. Psychopharmacology 205 (2009) 171
13. Receveur J.-M., Murray A., Linget J.-M., NØrregaard P.K., Cooper M., Bjurling E., Nielsen P.A., and Högberg T. Bioorg. Med. Chem. Lett. 20 (2010) 453
14. Jagerovic N., Fernandez-Fernandez C., and Goya P. Curr. Top. Med. Chem. 8 (2008) 205
15. Lee H.-K., Choi E.B., and Pak C.S. Curr. Top. Med. Chem. 9 (2009) 482
16. Reggio P.H. Curr. Pharm. Des. 9 (2003) 1607
17. Lange J.H.M., and Kruse C.G. Curr. Opin. Drug Discovery Dev. 7 (2004) 498
18. Lange J.H.M., and Kruse C.G. Drug Discovery Today 10 (2005) 693
19. Wang H., Duffy R.A., Boykow G.C., Chackalamannil S., and Madison V.S. J. Med. Chem. 51 (2008) 2439
20. Foloppe N., Benwell K., Brooks T.D., Kennett G., Knight A.R., Misra A., and Monck N.J.T. Bioorg. Med. Chem. Lett. 19 (2009) 4183
21. Lange J.H.M., van Stuivenberg H.H., Coolen H.K.A.C., Adolfs T.J.P., McCreary A.C., Keizer H.G., Wals H.C., Veerman W., Borst A.J.M., De Looff W., Verveer P.C., and Kruse C.G. J. Med. Chem. 48 (2005) 1823
22. Dyck B., Goodfellow V.S., Phillips T., Grey J., Haddach M., Rowbottom M., Naeve G.S., Brown B., and Saunders J. Bioorg. Med. Chem. Lett. 14 (2004) 1151
23. Smith R.A., Fathi Z., Achebe F., Akuche C., Brown S.E., Choi S., Fan J., Jenkins S., Kluender H.C.E., Konkar A., Lavoie R., Mays R., Natoli J., O'Connor S.J., Ortiz A.A., Su N., Taing C., Tomlinson S., Tritto T., Wang G., Wirtz S.N., Wong W., Yang X.F., Ying S., and Zhang Z. Bioorg. Med. Chem. Lett. 17 (2007) 2706
24. Lange J.H.M., van der Neut M.A.W., Wals H.C., Kuil G.D., Borst A.J.M., Mulder A., den Hartog A.P., Zilaout H., Goutier W., van Stuivenberg H.H., and van Vliet B. Bioorg. Med. Chem. Lett. 20 (2010) 1084
25. Snieckus V. Chem. Rev. 90 (1990) 879
26. Gadde K.M., and Allison D.B. Circulation 114 (2006) 974
27. Zhang Q., Ma P., Wang W., Cole R.B., and Wang G. Drug Metab. Dispos. 33 (2005) 508
28. European Medicines Agency Report on Acomplia: http://www.ema.europa.eu/humandocs/PDFs/EPAR/acomplia/H-666-en6.pdf, p 10).
29. Katoch-Rouse R., Pavlova O.A., Caulder T., Hoffman A.F., Mukhin A.G., and Horti A.G. J. Med. Chem. 46 (2003) 642
30. Schinkel A.H., Wagenaar E., van Deemter L., Mol C.A.A.M., and Borst P. J. Clin. Invest. 96 (1995) 1698
31. Kelder J., Grootenhuis P.D.J., Bayada D.M., Delbressine L.P.C., and Ploemen J.-P. Pharm. Res. 16 (1999) 1514
32. Clark D.E. Drug Discovery Today 8 (2003) 927
33. Bendels S., Kansy M., Wagner B., and Huwyler J. Eur. J. Med. Chem. 43 (2008) 1581
34. Irving, A. J.; McDonald, N. A.; Harkany, T. Cannabinoids and the brain; Köfalvi, A., Ed.; Springer US; New York, 2008, p 59.
35. Lipinski C.A., Lombardo F., Dominy B.W., and Feeney P.J. Adv. Drug Delivery Rev. 23 (1997) 3
36. Leeson P.D., and Springthorpe B. Nat. Rev. Drug Discovery 6 (2007) 881
37. Waring M.J. Expert Opin. Drug Discovery 5 (2010) 235
38. Ghose A.K., Viswanadhan V.N., and Wendoloski J.J. J. Phys. Chem. A 102 (1998) 3762
39. Lange J.H.M., van der Neut M.A.W., den Hartog A.P., Wals H.C., Hoogendoorn J., van Stuivenberg H.H., van Vliet B.J., and Kruse C.G. Bioorg. Med. Chem. Lett. 20 (2010) 1752
40. Dow R.L., Hadcock J.R., Scott D.O., Schneider S.R., Paight E.S., Iredale P.A., Carpino P.A., Griffith D.A., Hammond M., and DaSilva-Jardine P. Bioorg. Med. Chem. Lett. 19 (2009) 5351
41. Cavero I., Solomon T., Buckley J.P., and Jandhyala B.S. Res. Commun. Chem. Pathol. Pharmacol. 6 (1973) 527
42. Vollmer R.R., Cavero I., Ertel R.J., Solomon T.A., and Buckley J.P. J. Pharm. Pharmacol. 26 (1974) 186
43. Wagner J.A., Jarai Z., Batkai S., and Kunos G. Eur. J. Pharmacol. 423 (2001) 203
44. Brown C.M., Reisfeld B., and Mayeno A.N. Drug Metab. Rev. 40 (2008) 1
45. Cruciani G., Carosati E., De Boeck B., Ethirajulu K., Mackie C., Howe T., and Vianello R. J. Med. Chem. 48 (2005) 6970
46. Metasite™ version 3.0.6 (2009) was used. Validation of the method by the originators has shown that the primary site of metabolism was found in the top three Metasite predictions for more than 85% of the cases.
47. 6) δ 1.35-1.41 (m, 2H), 1.61-1.66 (m, 4H), 2.80-2.84 (m, 4H), 3.52 (s, 3H), 7.38 (d, J = 8 Hz, 2H), 7.42 (dd, J = 8 and 2 Hz, 1H), 7.46 (d, J = 8 Hz, 2H), 7.57 (d, J = 2 Hz, 1H), 7.62 (d, J = 8 Hz, 1H), 9.40 (s, 1H);