Synthesis and α4β2 nicotinic affinity of 2- pyrrolidinylmethoxyimines and prolinal oxime ethers

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 23, 2004, Pages 5827-5830

  Pallavicini, Marco ^a   Moroni, Barbara ^a   Bolchi, Cristiano ^a   Clementi, Francesco ^b   Fumagalli, Laura ^a   Gotti, Cecilia ^b   Vailati, Silvia ^b   Valoti, Ermanno ^a   Villa, Luigi ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b CNR   (Italy)

Author keywords

Affinity; Bioisostere; Ligand; nAChR; Neuronal nicotinic acetylcholine receptor; Nicotine; Oxime ether

Indexed keywords

2 ETHYLIDENEAMINOOXYMETHYL 1 METHYLPYRROLIDINE; 2 ISOPROPYLIDENEAMINOOXYMETHYL 1 METHYLPYRROLIDINE; 3 METHYL 5 (1 METHYL 2 PYRROLIDINYL)ISOXAZOLE; ETHER DERIVATIVE; IMINE; ISOXAZOLINE DERIVATIVE; LIGAND; MUSCARINIC RECEPTOR; NICOTINE; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG; DRUG DERIVATIVE; NICOTINIC RECEPTOR ALPHA4BETA2; PROLINAL; PROLINE; PYRROLIDINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; DRUG SELECTIVITY; DRUG SYNTHESIS; ANIMAL; BRAIN CORTEX; METABOLISM; PHYSIOLOGY; PROTEIN BINDING; RAT; SYNTHESIS;

ANIMALS; CEREBRAL CORTEX; IMINES; PROLINE; PROTEIN BINDING; PYRROLIDINES; RATS; RECEPTORS, NICOTINIC;

EID: 7244234606     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.09.044     Document Type: Article

References (29)

1. C. Gotti, D. Fornasari, and F. Clementi Prog. Neurobiol. 53 1997 199
2. J. Lindstrom Neuronal Nicotinic Receptors, Handbook of Experimental Pharmacology Vol. 144 2000 Springer Berlin
3. R.C. Hogg, M. Raggenbass, and D. Bertrand Rev. Physiol. Biochem. Pharmacol. 147 2003 1
4. J.D. Schmitt Curr. Med. Chem. 7 2000 749
5. J.E. Tønder, and P.H. Olesen Curr. Med. Chem. 8 2001 651
6. O. Nicolotti, M. Pellegrini-Calace, C. Altomare, A. Carotti, A. Carrieri, and F. Sanz Curr. Med. Chem. 9 2002 1
7. R.P. Sheridan, R. Nilakantan, J.S. Dixon, and R. Venkataragharan J. Med. Chem. 29 1986 899
8. R.B. Barlow, and O. Johnson Br. J. Pharmacol. 98 1989 799
9. D.T. Manallack, T. Gallagher, and D.J. Livingstone J. Devillers Neural Networks in QSAR and Drug Design Vol. 177-208 1996 Academic London
10. M.A. Abreo, N.-H. Lin, D.S. Garvey, D.E. Gunn, A.M. Hettinger, J.T. Wasicak, P.A. Pavlik, Y.C. Martin, D.L. Donnelly-Roberts, D.J. Anderson, J.P. Sullivan, M. Williams, S.P. Arneric, and M.W. Holladay J. Med. Chem. 39 1996 817
11. A. Groppetti, M.L. Zappia, O. Pirola, and S. Rossi Il Farmaco 21 1966 51
12. H. Tecle, D.J. Lauffer, R.E. Davis, T. Mirzadegan, D.W. Moreland, R.D. Schwarz, A.J. Thomas, C. Raby, D. Eubanks, M.R. Brann, and J.C. Jaean Bioorg. Med. Chem. Lett. 5 1995 637
13. R. Plate, J.M. Plaum, Th. de Boer, and J.S. Andrews Bioorg. Med. Chem. 4 1996 239
14. Cereda, E.; Pellegrini, C.; Sagrada, A.; Schiavi, G. B. WO 94/00448, 1994; Chem. Abstr. 1994, 122, 290728
15. D.S. Garvey, J.T. Wasicak, M.W. Decker, J.D. Brioni, M.J. Buckley, J.P. Sullivan, G.M. Carrera, M.W. Holladay, S.P. Arneric, and M. Williams J. Med. Chem. 37 1994 1055
16. C.F. Hammer, S.R. Heller, and J.H. Craig Tetrahedron 28 1972 239 253
17. 3 95/5/1
18. 3 shows the presence of comparable quantities of both the ammonium and the oxyimmonium species
19. 3, 300 MHz): δ 7.43 (q, J = 6.2 Hz, ∼0.5H), 6.74 (q, J = 5.5 Hz, ∼0.5H), 4.14 (dd, J = 11.0, 6.2 Hz, ∼0.5H), 4.08 (dd, J = 10.6, 5.5 Hz, ∼0.5H), 4.04 (dd, J = 11.0, 5.5 Hz, ∼0.5H), 3.98 (dd, J = 10.6, 5.5 Hz, ∼0.5H), 3.08 (m, 1H), 2.48-2.60 (m, 1H), 2.43 (s, ∼1.5H), 2.41 (s, ∼1.5H), 2.25 (m, 1H), 1.84 (d, J = 6.2 Hz, 3H), 2.00-1.56 (m, 4H)
20. 3, 300 MHz): δ 10.95 (br s, 1H), 8.89 (s, 2H), 6.79 (q, J = 5.5 Hz, 1H), 4.66 (dd, J = 8.8, 13.0 Hz, 1H), 4.34 (dd, J = 13.0, 2.9 Hz, 1H), 3.98 (m, 1H), 3.62 (m, 1H), 3.06 (s, 3H), 2.99 (m, 1H), 2.29 (m, 2H), 2.12 (m, 2H), 1.80 (d, J = 5.5 Hz, 3H)
21. 3 97/3/0.5
22. 3, 300 MHz): δ 6.71 (d, J = 5.9 Hz, 1H), 4.30 (septet, J = 6.2 Hz, 1H), 3.39 (dd, J = 15.1, 7.0 Hz, 1H), 3.07 (m, 1H), 2.33 (s, 3H), 2.18 (dd, J = 18.6, 8.1 Hz, 1H), 2.10-2.20 (m, 1H), 1.72-1.92 (m, 2H), 1.61 (m, 1H), 1.22 (d, J = 6.2 Hz, 6H)
23. 1H NMR identical to that of (Z)-(S)-3
24. G.C. Kleinspehn, J.A. Jung, and S.A. Studniarz J. Org. Chem. 32 1967 460 462
25. C.E. Holloway, and C.P.J. Vuik Tetrahedron Lett. 1979 1017 1020
26. G.J. Karabatsos, R.A. Taller, and F.M. Vane J. Am. Chem. Soc. 85 1963 2326 2327
27. G.J. Karabatsos, and N. His Tetrahedron 23 1967 1079 1095
28. L. Li, W. Zhong, N. Zacharias, C. Gibbs, H.A. Lester, and D.A. Dougherty Chem. Biol. 8 2001 47
29. The conformational analyses were performed using Monte Carlo approach that produced 1000 conformers for each molecule by rotating its flexible torsions. All the obtained geometries were optimized and clustered according to their similarity