Benzofuran derivatives as a novel class of inhibitors of mTOR signaling

European Journal of Medicinal Chemistry

Volumn 74, Issue , 2014, Pages 41-49

  Salomé, Christophe ^a   Narbonne, Vanessa ^a   Ribeiro, Nigel ^a   Thuaud, Frédéric ^a   Serova, Maria ^b   De Gramont, Armand ^b   Faivre, Sandrine ^b   Raymond, Eric ^b   Désaubry, Laurent ^a  

^a UNIVERSITÉ DE STRASBOURG   (France)

^b BEAUJON HOSPITAL   (France)

Author keywords

Benzofuran; Cytotoxicity; mTOR; mTORC1

Indexed keywords

(5 METHOXYBENZOFURAN 2 YL)(PHENYL)METHANONE; 1 [(2 BENZYL 5 HYDROXYBENZOFURAN 4 YL)METHYL]PIPERIDIN 3 OL; 1 [(2 BENZYL 5 HYDROXYBENZOFURAN 4 YL)METHYL]PIPERIDIN 4 OL; 1 [(2 BENZYL 5 HYDROXYBENZOFURAN 4 YL)METHYL]PIPERIDINE 4 CARBOXAMIDE; 1' [(2 BENZYL 5 HYDROXYBENZOFURAN 4 YL)METHYL] N [2 (2 HYDROXYETHOXY)ETHYL] [1,4' BIPIPERIDINE] 4 CARBOXAMIDE; 2 BENZOYLBENZOFURAN 5 OL; 2 BENZYL 4 (MORPHOLINOMETHYL)BENZOFURAN 5 OL; 2 BENZYL 4 [(3,4 DIHYDROISOQUINOLIN 2(1H) YL)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [(4 BENZYLPIPERAZIN 1 YL)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [(4 METHYLPIPERAZIN 1 YL)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [(4 PHENYLPIPERIDIN 1 YL)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [(DIETHYLAMINO)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [(DIMETHYLAMINO)METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[(2 HYDROXYETHYL)(METHYL)AMINO]METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[4 (PYRROLIDIN 1 YL)PIPERIDIN 1 YL]METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[4 [2 (2 HYDROXYETHOXY)ETHYL]PIPERAZIN 1 YL] METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[BENZYL(METHYL)AMINO]METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[CYCLOHEXYL(METHYL)AMINO]METHYL]BENZOFURAN 5 OL; 2 BENZYL 4 [[METHOXY(METHYL)AMINO]METHYL]BENZOFURAN 5 OL; 2 BENZYL 5 METHOXYBENZOFURAN; 2 BENZYLBENZOFURAN 5 OL; 2,2' [[(2 BENZYL 5 HYDROXYBEZOFURAN 4 YL)METHYL]AZANEDIYL]DIETHANOL; 4 [(1,4' BIPIPERIDIN) 1' YLMETHYL] 2 BENZYLBENZOFURAN 5 OL; 4 [(1,4' BIPIPERIDIN) 1' YLMETHYL] 2 PHENYLBENZOFURAN 5 OL; 4 [(1,4' BIPIPERIDIN) 1' YLMETHYL]2 [HYDROXY(PHENYL)METHYL]BENZOFURAN 5 OL; 4 [(2 BENZYL 5 HYDROXYBENZOFURAN 4 YL)METHYL]PIPERAZINE 1 CARBALDEHYDE; [4 [(1,4' BIPIPERIDIN) 1' YLMETHYL] 5 HYDROXYBENZOFURAN 2 YL](PHENYL)METHANONE; BENZOFURAN DERIVATIVE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER CELL CULTURE; CARBON NUCLEAR MAGNETIC RESONANCE; CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IC 50; IN VITRO STUDY; LIVER CELL CARCINOMA; PROTON NUCLEAR MAGNETIC RESONANCE; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

BENZOFURAN; CYTOTOXICITY; MTOR; MTORC1;

BENZOFURANS; CELL LINE, TUMOR; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; MAGNETIC RESONANCE SPECTROSCOPY; SIGNAL TRANSDUCTION; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TOR SERINE-THREONINE KINASES;

EID: 84892704829     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2013.12.020     Document Type: Article

References (13)

1. S. Albert, M. Serova, C. Dreyer, M.P. Sablin, S. Faivre, and E. Raymond New inhibitors of the mammalian target of rapamycin signaling pathway for cancer Expert Opin. Investig. Drugs 19 2010 919 930
2. S. Faivre, G. Kroemer, and E. Raymond Current development of mTOR inhibitors as anticancer agents Nat. Rev. Drug. Discov. 5 2006 671 688
3. S. Vignot, S. Faivre, D. Aguirre, and E. Raymond mTOR-targeted therapy of cancer with rapamycin derivatives Ann. Oncol. 16 2005 525 537
4. T.R. Kau, F. Schroeder, S. Ramaswamy, C.L. Wojciechowski, J.J. Zhao, T.M. Roberts, J. Clardy, W.R. Sellers, and P.A. Silver A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells Cancer Cell. 4 2003 463 476
5. I. Smukste, and B.R. Stockwell Restoring functions of tumor suppressors with small molecules Cancer Cell. 4 2003 419 420
6. J.F. Cheng, B.N. Nguyen, X. Liu, G.D. Lopaschuk, J.R. Dyck, Preparation of Heterocyclic Compounds Useful as Malonyl-CoA Decarboxylase Inhibitors, US 7696365 B2, 2005.
7. 3CN-TMSCl Tetrahedron Lett. 39 1998 7059 7062
8. V.M. Lyubchanskaya, V.S. Velezheva, I.S. Nikolaeva, E.A. Golovanova, L.M. Alekseeva, and A.N. Fomina 2-Benzyl(isobutyl)-5-hydroxybenzofuran derivatives: synthesis and antiviral activity Khim.-Farm. Zh. 23 1989 843 847
9. K.E. O'Reilly, F. Rojo, Q.-B. She, D. Solit, G.B. Mills, D. Smith, H. Lane, F. Hofmann, D.J. Hicklin, D.L. Ludwig, J. Baselga, and N. Rosen mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res. 66 2006 1500 1508
10. S.V. Bhagwat, P.C. Gokhale, A.P. Crew, A. Cooke, Y. Yao, C. Mantis, J. Kahler, J. Workman, M. Bittner, L. Dudkin, D.M. Epstein, N.W. Gibson, R. Wild, L.D. Arnold, P.J. Houghton, and J.A. Pachter Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin Mol. Cancer Ther. 10 2011 1394 1406
11. I. Kim, K. Kim, and J. Choi A direct approach to 5-hydroxybenzofurans via a platinum-catalyzed domino rearrangement/5-endo-dig cyclization reaction of quinols J. Org. Chem. 74 2009 8492 8495
12. J.F. Cheng, B.N. Nguyeng, X. Liu, G.D. Lopaschuk, J. Dyck, Heterocyclic Compounds Useful as Malonyl-CoA Decarboxylase Inhibitors, US 20050026969, 2005.
13. K. Yoshihara, D. Suzuki, Y. Susumu, Y. Hiroyoshi. M. Hisashi, S. Norio, Preparation of Guanidine Compounds as VAP-1 Inhibitors, PCT Int. Appl. WO 2012124696, 2012.