2-(Arylmethyl)-3-substituted quinuclidines as selective α7 nicotinic receptor ligands

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 8, 2005, Pages 2073-2077

  Mazurov, Anatoly ^a   Klucik, Jozef ^a   Miao, Lan ^a   Phillips, Teresa Y ^a   Seamans, Angela ^a   Schmitt, Jeffrey D ^a   Hauser, Terry A ^a   Johnson Jr , Raymond T ^a   Miller, Craig ^a  

^a TARGACEPT INC   (United States)

Author keywords

Quinuclidine; 7 Nicotinic receptor ligands

Indexed keywords

AMIDE; CARBAMIC ACID; LIGAND; N (1 AZABICYCLO[2.2.2]OCT 3 YL)BENZO[B]FURAN 2 CARBOXAMIDE; NICOTINIC AGENT; NICOTINIC RECEPTOR; QUINUCLIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CENTRAL NERVOUS SYSTEM; CONCENTRATION (PARAMETERS); DESENSITIZATION; GANGLION; HUMAN; MUSCLE; NONHUMAN; PHARMACOPHORE;

EID: 16244422671     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.02.045     Document Type: Article

References (37)

1. M. Bencherif, and J.D. Schmitt Curr. Drug Targets-CNS Neurological Disord. 1 2002 349
2. J.D. Schmitt Curr. Med. Chem. 7 2000 749
3. J.D. Schmitt, and M. Bencherif Ann. Rep. Med. Chem. 35 2000 41
4. M.B. Marrero, R.L. Papke, B.S. Bhatti, S. Shaw, and M. Bencherif J. Pharmacol. Exp. Ther. 309 2004 16
5. L. Toma, D. Barlocco, and A. Gelain Exp. Opin. Ther. Pat. 14 2004 1029
6. W.H. Bunnelle, M.J. Dart, and M.R. Schrimpf Curr. Topics Med. Chem. 4 2004 299
7. M. Bencherif, M.E. Lovette, K.W. Fowler, S. Arrington, L. Reeves, W.S. Caldwell, and P.M. Lippiello J. Pharmacol. Exp. Ther. 279 1996 1413
8. M. Bencherif, A.J. Bane, C.H. Miller, G.M. Dull, and G.J. Gatto Eur. J. Pharmacol. 409 2000 45
9. R.L. Papke, J.C. Webster, P.M. Lippiello, M. Bencherif, and M.M. Francic J. Neurochem. 75 2000 204
10. G. Gatto, G.A. Bohme, W.S. Caldwell, S.R. Letchworth, V.M. Traina, M.C. Obinu, M. Laville, M. Reibaud, L. Pradier, G. Dunbar, and M. Bencherif CNS Drug Rev. 10 2004 147
11. B. S.; Hawkins, G. D.; Breining, S. R.; Phillips, T. Y.; Mazurov, A. A.; Miller, C. H. Abstract of Papers, 228th National Meeting of the American Chemical Society, Philadelphia, PA; American Chemical Society: Washington, DC, 2004; Abstract 11
12. M. Van Kampen, K. Selbach, R. Schneider, E. Schiegel, F. Boess, and R. Schreiber Psychopharmacology 172 2004 375
13. Schmitt, J. D.; Crooks, P. A.; Dull, G. M. U.S. Patent 6,432,975, Chem. Abstr. 2002, 136, 202100
14. B. Gauthier, J. Ranault, R. Cavier, P. Gayral, and G. Dreyfuss Ann. Pharm. Fr. 38 1980 359
15. Macor, J.; Wu, E. PCT Int. Appl., WO 9730998, 1997; Chem. Abstr. 1997, 131, 579721
16. R. Naito, M. Takeuchi, K. Morihira, M. Hayakawa, K. Ikeda, T. Shibanuma, and Y. Isomura Chem. Pharm. Bull. 46 1998 1286
17. M. Langlois, J.L. Soulier, M. Allainmat, S. Shen, and C. Gallais Bioorg. Med. Chem. Lett. 3 1993 1555
18. R.L. Papke, and J.S. Thinschmidt Neurosci. Lett. 256 1998 163
19. G. Mullen, J. Napier, M. Balestra, T. DeCory, G. Hale, J. Macor, R. Mack, J. Loch III, E. Wu, A. Kover, P. Verhoest, A. Sampognaro, E. Phillips, Y. Zhu, R. Murray, R. Griffith, J. Blosser, D. Gurley, A. Machulskis, J. Zongrone, A. Rosen, and J. Gordon J. Med. Chem. 43 2000 4045
20. Papke, R. L. Personal communication
21. Stereoselective reduction of 2-substituted quinuclidin-3-ones with aluminum isopropoxide under nonequilibrating conditions and formation of predominantly cis-isomer has been documented in a few articles, for example, E.J. Warawa, N.J. Mueller, and R. Jules J. Med. Chem. 17 1974 497
22. C.J. Swain, E.M. Seward, M.A. Cascieri, T.M. Fong, R. Herbert, D.E. MacIntyre, K.J. Merchant, S.N. Owen, A.P. Owens, V. Sabin, M. Teall, M.B. VanNiel, B.J. Williams, S. Sadowski, C. Strader, R.G. Ball, and R. Baker J. Med. Chem. 38 1995 4793
23. For a discussion of stereochemical assignments and NMR data on analogous 2-benzylquinuclidin-3-ol, see E.J. Warawa, and J.R. Campbell J. Org. Chem. 39 1974 3511
24. Reductive amination of 2-substituted quinuclidin-3-ones results in formation of cis-isomer as a major product, see G. Viti, D. Giannotti, R. Nanncini, G. Balacco, and V. Pestellini Tetrahedron Lett. 35 1994 5939
25. E.J. Warawa, N.J. Mueller, and J.S. Fleming J. Med. Chem. 18 1975 587
26. Phillips, E.; Schmiesing, R., PCT Int. Appl. WO2001060821; Chem. Abstr. 2001, 135, 180708
27. Meyers, J. K.; Rogers, B. N.; Groppi, V. E.; Piotrowski, D. W.; Bodnar, A. L.; Jacobsen, E. J.; Corbett, J. W.; PCT Int. Appl. WO2002015662; Chem. Abstr. 2002, 136, 200333
28. Myers, J. K.; Groppi, V. E.; Piotrowski, D. W.; PCT Int. Appl. WO2002016356; Chem. Abstr. 2002, 136, 200335
29. Nozulak, J., PCT Int. Appl. WO2001085727; Chem. Abs. 2001, 135, 358082
30. Mazurov, A.; Klucik, J.; Miao, L.; Phillips, T. Y.; Seamans, A.; Schmitt, J. D.; Miller, C. Abstract of Paper, 228th National Meeting of the American Chemical Society, Society, Philadelphia, PA; American Chemical Society: Washington, DC, 2004; Abstract 83
31. Mazurov, A. A.; Klucik, J.; Miao, L.; Seamans, A. S.; Phillips, T. Y.; Schmitt, J. J. D.; Miller, C. H. U.S. Patent Appl. Publ. US 2004002513; Chem. Abstr. 2004, 140, 77298
32. i = 41.8 nM)
33. 3OD): cis-8l, 1.98-2.42 (m, 5H), 3.40-3.87 (m, 6H), 4.32 (m, 1H), 4.55 (dd, 1H), 7.38 (m, 1H), 7.52 (m, 2H), 7.62 (m, 1H), 7.78 (d, 1H), 7.99 (m, 1H), 8.65 (d, 1H), 8.87 (d, 1H), 9.17 (s, 1H); trans-8l, 1.92-2.48 (m, 5H), 3.20-3.58 (m, 6H), 3.81 (m, 1H), 4.54 (dd, 1H), 7.39 (m, 1H), 7.55 (m, 3H), 7.72 (m, 2H), 8.00 (d, 1H), 8.47 (d, 1H), 8.6 (s, 1H)
34. i Values were determined from one to three competitive inhibition curves for each compound. Seven to eleven concentrations of each compound were utilized to define each inhibition curve with triplicate samples at each concentration. Where multiple competitive inhibition curves were available, SEM has been calculated and provided
35. A.R.L. Davies, D.J. Hardick, I.S. Blagbrough, B.V.L. Potter, A.J. Wolstenholme, and S. Wonnacott Neuropharmacology 38 1999 679
36. M. Bencherif, A.J. Bane, C.H. Miller, G.M. Dull, and G.J. Gatto Eur. J. Pharm. 409 2000 45
37. X. Pei, T.H. Gupta, B. Badio, W.L. Padgett, and J.W. Daly J. Med. Chem. 41 1998 2047