Synthesis and SAR study of diphenylbutylpiperidines as cell autophagy inducers

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 1, 2011, Pages 234-239

  Chen, Gang ^a   Xia, Hongguang ^a   Cai, Yu ^a   Ma, Dawei ^a   Yuan, Junying ^a,b   Yuan, Chengye ^a  

^a SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY   (China)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Autophagy; Diphenylbutylpiperidines; Inducers; SAR study; Synthesis

Indexed keywords

DIPHENYLBUTYLPIPERIDINE DERIVATIVE;

ARTICLE; AUTOPHAGY; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

AUTOPHAGY; CELL LINE, TUMOR; HUMANS; PIPERIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78650511065     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.11.029     Document Type: Article

References (29)

1. T. Shintani, and D.J. Klionsky Science 306 2004 990
2. N. Mizushima, B. Levine, A.M. Cuervo, and D.J. Klionsky Nature 451 2008 1069
3. J.J. Lum, R.J. DeBerardinis, and C.B. Thompson Nat. Rev. Mol. Cell. Biol. 6 2005 439
4. T. Hara, K. Nakamura, M. Matsui, A. Yamamoto, Y. Nakahara, R. Suzuki-Migishima, M. Yokoyama, K. Mishima, I. Saito, H. Okano, and N. Mizushima Nature 441 2006 885
5. L. Zhang, J. Yu, H. Pan, P. Hu, Y. Hao, W. Cai, H. Zhu, A. Yu, X. Xie, D. Ma, and J. Yuan Proc. Natl. Acad. Sci. U.S.A. 104 2007 19023
6. A. Williams, S. Sarkar, P. Cuddon, E.K. Ttofi, S. Saiki, F.H. Siddiqi, L. Jahreiss, A. Fleming, D. Pask, P. Goldsmith, C.J. O'Kane, R.A. Floto, and D.C. Rubinsztein Nat. Chem. Biol. 4 2008 295
7. H. Xia, L. Zhang, G. Chen, T. Zhang, J. Liu, M. Jin, X. Ma, D. Ma, and J. Yuan Autophagy 6 2010 1
8. P. Seeman, T. Lee, M. Chau-Wong, and K. Wong Nature 261 1976 717
9. R.J. Gould, K.M.M. Murphy, I.J. Reynolds, and S.H. Snyder Proc. Natl. Acad. Sci. U.S.A. 80 1983 5122
10. C.J. Grantham, M.J. Main, and M.B. Cannell Br. J. Pharmacol. 111 1994 483
11. D.W.Y. Sah, and B.P. Bean Mol. Pharmacol. 45 1994 84
12. J.J. Enyeart, B.A. Biagi, R.N. Day, S.S. Sheu, and R.A. Maurer J. Biol. Chem. 265 1990 16373
13. J.P. Galizzi, M. Fosset, G. Romey, P. Laudron, and M. Lazdunski Proc. Natl. Acad. Sci. U.S.A. 83 1986 7513
14. V.F. King, M.L. Garcia, J.L. Shevell, R.S. Slaughter, and G.J. Kaczorowski J. Biol. Chem. 264 1989 5633
15. J.W. Hulshof, H.F. Vischer, H.F. Verheij, M.H.P. Fratantoni, M.J. Smit, I.J.P. de Esch, and R. Leurs Bioorg. Med. Chem. 14 2006 7213
16. K. Sindelar, M. Rajsner, I. Cervena, V. Valenta, J.O. Jilek, B. Kakac, J. Holubek, E. Svatek, F. Miksik, and M. Protiva Collect. Czech. Chem. Commun. 38 1973 3879
17. C. Botteghi, M. Marchetti, S. Paganelli, and F. Persi-Paoli Tetrahedron 57 2001 1631
18. J.W. Hulshof, P. Casarosa, M.P.B. Menge, L.M. Kuusisto, H. van der Goot, M.J. Smit, I.J.P. de Esch, and R. Leurs J. Med. Chem. 48 2005 6461
19. M. Rajsner, A. Dlabac, and M. Protira Collect. Czech. Chem. Commun. 46 1981 1530
20. For the synthesis of the left side of compound 12b, see Ref.: S.S. Kulp, V.B. Fish, and N.R. Easton J. Med. Chem. 6 1963 516
21. The structure of the left side of compound 12d is the same as compound 5 (R = 4-F).
22. The carboxylic acid group in the left of compound 12e can be prepared from compound 4 (R = 4-F) by hydrogenation, Jones oxidation.
23. For the synthesis of these left sides of compounds 12f-i, see Ref.: P.A.J. Janssen, C. van der Westeringh, A.H.M. Jageneau, P.J.A. Demoen, B.K.F. Hermans, G.H.P. van Daele, K.H.L. Schellekens, C.A.M. van der Eycken, and C.J.E. Niemegeerx J. Med. Chem. 1 1959 281
24. The left side of compound 12j can be synthesized from the same route as showed in Scheme 1 with the starting material δ-valerolactone instead of γ-butyrolactone.
25. N. Kashali, M.F. Polat, R. Altundas, and Y. Kara Helv. Chim. Acta 91 2008 67
26. In this Letter we mainly used the left side with three carbon chain due to its easy preparation.
27. 3) by removing the Boc group with trifluoroacetic acid, and hydrogenation of compound 16e can give compound 16f.
28. The right side of compound 16j is commercially available.
29. N. Castagnoli Jr., J.M. Rimoldi, J. Bloomquist, and K.P. Castagnoli Chem. Res. Toxicol. 10 1997 924