Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X7 receptor

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6370-6374

  Abberley, Lee ^a   Bebius, Aude ^a   Beswick, Paul J ^a   Billinton, Andy ^a   Collis, Katharine L ^a   Dean, David K ^a   Fonfria, Elena ^a   Gleave, Robert J ^a   Medhurst, Stephen J ^a   Michel, Anton D ^a   Moses, Andrew P ^a   Patel, Sadhana ^a   Roman, Shilina A ^a   Scoccitti, Tiziana ^a   Smith, Beverley ^a   Steadman, Jon G A ^a   Walter, Daryl S ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Antagonist; P2X7; Pain

Indexed keywords

2 OXO N (PHENYLMETHYL) 4 IMIDAZOLIDINECARBOXAMIDE; CELECOXIB; PURINERGIC P2X7 RECEPTOR; PURINERGIC RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTHRALGIA; ARTICLE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG IDENTIFICATION; IN VIVO STUDY; NONHUMAN; RAT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; HALF-LIFE; HAPLORHINI; IMIDAZOLINES; PURINERGIC ANTAGONISTS; RATS; RECEPTORS, PURINERGIC P2X7;

EID: 77958031377     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.101     Document Type: Article

References (35)

1. G. Collo, S. Neidhart, E. Kawashima, M. Kosco-Vibois, R.A. North, and G. Buell Neuropharmacology 36 1997 1277
2. F. DiVirgilio, V. Vishwanath, and D. Ferrari M.P. Abbraccio, M. Williams, Handbook of Experimental Pharmacology Vol. 151 2001 Springer 355 373
3. H.P. Buisman, T.H. Steinberg, J. Fischbarg, S.C. Silverstein, S.A. Vogelzang, C. Ince, D.L. Ypey, and P.C. Leijh Proc. Natl. Acad. Sci. U.S.A. 85 1988 7988
4. D. Ferrari, C. Pizzirani, E. Adinolfi, R.M. Lemoli, A. Curti, M. Idzko, E. Panther, and F. Di Virgilio J. Immunol. 176 2006 3877
5. D. Fields, and G. Burnstock Nat. Rev. Neurosci. 7 2006 423
6. I.P. Chessel, J.P. Hatcher, C. Bountra, A.D. Michel, J.P. Hughes, P. Green, J. Egerton, M. Murfin, J. Richardson, W.L. Peck, C.B.A. Grahames, M.A. Casula, Y. Yiangou, R. Birch, P. Anand, and G.N. Buell Pain 114 2005 386
7. P.M. Honore, D. Donnelly-Roberts, M. Namovic, G. Hsieh, C. Zhu, J. Mikusa, G. Hernandez, C. Zhong, D.M. Gauvin, P. Chandran, R. Harris, A.P. Medrano, W. Carroll, K. Marsh, J.P. Sullivan, C.R. Faltynek, and M.F. Jarvis J. Pharmacol. Exp. Ther. 319 2006 1376
8. D.C. Broom, D.J. Matson, E. Bradshaw, M.E. Buck, R. Meade, S. Coombs, M. Matchett, K.K. Ford, W. Yu, J. Yuan, S.H. Sun, R. Ochoa, J.E. Krause, D.J. Wustrow, and D.N. Cortright J. Pharmacol. Exp. Ther. 327 2008 620
9. A. Perez-Medrano, D.L. Donnelly-Roberts, P. Honore, G.C. Hsieh, M.T. Namovic, S. Peddi, Q. Shuai, Y. Wang, C.R. Faltynek, M.F. Jarvis, and W.A. Carroll J. Med. Chem. 52 2009 3366
10. D.W. Nelson, R.J. Gregg, M.E. Kort, A. Perez-Medrano, E.A. Voight, Y. Wang, G. Grayson, M.T. Namovic, D.L. Donnelly-Roberts, W. Niforatos, P. Honore, M.F. Jarvis, C.R. Faltynek, and W.A. Carroll J. Med. Chem. 49 2006 3659
11. W.A. Carroll, D. Donnelly-Roberts, and M.F. Jarvis Purinergic Signalling 5 2009 63
12. R. Romagnoli, P.G. Baraldi, O. Cruz-Lopez, C. Lopet-Cara, D. Preti, P.A. Borea, and S. Gessi Expert Opin. Ther. Targets 12 2008 647
13. L.J. Chambers, A.J. Stevens, A.P. Moses, A.D. Michel, B. Slingsby, D.S. Walter, D.J. Davies, D.J. Livermore, E. Fonfria, E.H. Demont, M. Vimal, P.J. Theobald, P.J. Beswick, R.J. Gleave, S.A. Roman, S. Senger, and S. Roomans Bioorg. Med. Chem. Lett. 20 2010 3161
14. P.J. Beswick, A. Billinton, L.J. Chambers, D.K. Dean, E. Fonfria, R.J. Gleave, S.J. Medhurst, A.D. Michel, A.P. Moses, S. Patel, S.A. Roman, S. Roomans, S. Senger, A.J. Stevens, and D.S. Walter Bioorg. Med. Chem. Lett. 20 2010 4653
15. M.H. Abdi, P.J. Beswick, A. Billinton, L.J. Chambers, A. Charlton, S.D. Collins, K.L. Collis, D.K. Dean, E. Fonfria, R.J. Gleave, C.L. Lejeune, D.G. Livermore, S.J. Medhurst, A.D. Michel, A.P. Moses, L. Page, S. Patel, S.A. Roman, S. Senger, B. Slingsby, J.G.A. Steadman, A.J. Stevens, and D.S. Walter Bioorg. Med. Chem. Lett. 20 2010 5080
16. C. Abad-Zapatero Expert Opin. Drug Disc. 2 2007 469
17. P.D. Leeson, and B. Springthorpe Nat. Rev. Drug Disc. 6 2007 881
18. The same concept was independently proposed by researchers at Pfizer and termed lipE T. Ryckmans, M.P. Edwards, V.A. Horne, A. Monica Correia, D.R. Owen, L.R. Thompson, I. Tran, M.F. Tutt, and T. Young Bioorg. Med. Chem. Lett. 15 2009 4406
19. Details of clinical studies with compound 2 will be disclosed in a future publication.
20. All experiments were performed in accordance with the United Kingdom Animals (Scientific Procedures) Act, 1986 under Project Licence as well as under the review and approval of the GlaxoSmithKline Procedures Review Panel. GlaxoSmithKline safety regulations were adhered to at all times.
21. Compounds shown in Table 2 were prepared using the methods described in WO2008 003697 A1, WO 2008 119685 A1, and WO 2008 119825 A1.
22. max values of 100%. Full details of the assay protocol can be found in patent application WO 2007 141267 A1. All reported pIC50s deviate from the mean value by <0.3.
23. S.E. Clarke, and P. Jeffrey Xenobiotica 31 2001 591
24. See WO 2008 119825 A1 for full experimental details.
25. S. Saijo, M. Wada, J.-I. Himizu, and A. Ishida Chem. Pharm. Bull. 28 1980 1459
26. M.P. Doyle, and J.T. Colyer Tetrahedron: Asymmetry 14 2003 3601
27. K. Hayashi, K. Nunami, J. Kato, N. Yoneda, M. Kubo, T. Ochiai, and R. Ishida J. Med. Chem. 32 1989 289
28. F. Lombardo, R.S. Obach, M.Y. Shalaeva, and F. Gao J. Med. Chem. 47 2004 1242
29. S.A. Hitchcock, and L.D. Pennington J. Med. Chem. 49 2006 7560
30. Calculated log D values were obtained using ACD Labs software v8.0.
31. Q. Wang, J.D. Rager, K. Weinstein, P.S. Kardos, G.L. Dobson, J. Li, and I.J. Hidalgo Int. J. Pharm. 288 2005 349
32. http://www.cerep.fr.
33. FeSSIF: Fed-state-simulated intestinal fluid E. Galia, E. Nicolaides, D. Horter, R. Lobenberg, C. Reppas, and J.B. Dressman Pharm. Res. 15 1998 698
34. A.W. Wilson, S.J. Medhurst, C.I. Dixon, N.C. Bontoft, L.A. Winyard, K.T. Brackenborough, J. De Alba, C.J. Clarke, M.J. Gunthorpe, G.A. Hicks, C. Bountra, D.S. McQueen, and I.P. Chessell Eur. J. Pain 10 2006 537
35. B. Sperlagh, E.S. Vizi, K. Wirkner, and P. Illes Prog. Neurobiol. 78 2006 327