2-Aminophenones, a common precursor to &ITN&IT-aryl isatins and acridines endowed with bioactivities

TETRAHEDRON

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Article

Brikci-Nigassa, Nahida Mokhtari^1,2  Bentabed-Ababsa, Ghenia²  Erb, William¹  Chevallier, Floris¹  Picot, Laurent³  Vitek, Lucille³  Fleury, Audrey³  Thiery, Valerie³  Souab, Mohamed⁴  Robert, Thomas⁴  Ruchaud, Sandrine⁴  Bach, Stephane⁴  Roisnel, Thierry¹  Mongin, Florence¹ 

[1] Univ Rennes, CNRS, ISCR, UMR 6226, F-35000 Rennes, France

[2] Univ Oran 1 Ahmed Ben Bella, Fac Sci Exactes & Appl, Lab Synth Organ Appl, BP 1524 El Mnaouer, Oran 31000, Algeria

[3] Univ La Rochelle, UMRi CNRS 7266, Lab Littoral Environm & Soc, F-17042 La Rochelle, France

[4] UPMC Univ Paris 06, Sorbonne Univ, CNRS,USR3151,Stn Biol Roscoff, Prot Phosphorylat & Human Dis Unit,Plateforme Cri, Pl Georges Teissier, F-29688 Roscoff, France

关键词: Isatin;    Acridin;    N-arylation;    Copper;    Kinase inhibition;    Antiproliferative activity;    Melanoma cells;   

DOI  :  10.1016/j.tet.2018.02.038

来源: Elsevier

【 摘 要 】

Because N-arylation of isatin only worked with iodoferrocene (and in low yield), we employed N-arylation of 2-aminophenones and subsequent oxidative cyclization to access various N-arylated isatins. In the course of this work, we observed that N-arylation using 2-iodofuran, 2-iodobenzofuran and 2-iodobenzothiophene did not lead to the expected derivatives, but to (benzo)furo- and (benzo)thieno [2,3-b]quinolines. Separate cyclization was also performed under acidic conditions on 2-(arylamino) phenones in order to obtain acridines and related compounds. Most of the synthesized compounds were screened for their antiproliferative activity in A2058 melanoma cells, and against a panel of disease-relevant kinases such as mammalian CDK5/p25, PIM1, CLK1, DYRK1A, GSK3 alpha/beta, Haspin and leishmanial CK1. The biological results are reported. (C) 2018 Elsevier Ltd. All rights reserved.

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