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Reactivity under Microwave Irradiation of 2-Amino 4H-chromene-3-carbonitrile as Tool for the Construction of Potential Bioactive Derivatives
* 1 , 2 , 2 , 2 , 2 , 1 , 3 , 3 , 4 , 4
1  Institut des Sciences Chimiques de Rennes, ISCR UMR 6226, groupe CORINT, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, 263 Av. du Gén. Leclerc, CS 74205, 35042 Rennes Cedex (France)
2  Laboratoire de Chimie Appliquée: Hétérocycles Corps Gras & Polymères, Université de Sfax, Route Soukra BP 1171, 3000 Sfax (Tunisie)
3  ImPACcell platform, SFR Biosit, Université de Rennes 1, Bât. 8, Campus de Villejean, 2 Av. du Prof. Léon Bernard, CS 34317, 35043 Rennes Cedex (France)
4  Station Biologique de Roscoff, USR 3151, CNRS-UPMC, Kissf platform, Place Georges Tessier, BP 74, 29682 Roscoff (France)

Published: 01 November 2017 by MDPI in 3rd International Electronic Conference on Medicinal Chemistry session ECMC-3

4H-Chromenes (or 4H-benzopyranes) and their derivatives are components of many naturally occurring products, which have also been submitted to structural modifications to increase molecular diversity for potential medicinal properties. In this context and starting from the 2-amino-2H-benzopyran-3-carbonitrile platform, it was possible to built easily (20 min.) a new class of 4-imino-3-phenyl-3,4-dihydro-1H-chromeno[2,3-d]pyrimidine-2(5H)-thiones (55-70%) under microwave irradiation at 120°C in pyridine medium. Treatment of the amino-4H-chromene platform with orthoester gave the corresponding methanimidate intermediate, which is converted into formamidine derivatives (63-85%) from various cyclic secondary amines or into N-3 substituted 4H-benzopyrano[2,3-d]pyrimidine-4(5H)-imines (49-94%) under microwave irradiation (50-120 °C, 30 min.). The biological properties of all products were explored by in vitro cancer assays against a panel of seven tumor cell lines (Huh 7D12, Caco2, MDA-MB231, HCT116, PC3, NCI-H727, HaCat, fibroblasts which are representative of different cancers: leukemia, melanona, and cancers of liver, colon, breast, prostate, lung, and kidney) and also by in vitro Serine/Threonine protein kinase inhibition assays (HsCDK5-p25, GSK3a/b, CLK1, HsHaspin, HsPIM1, HsAurora B). Some of these 2-imino- or 2-amino-2H-benzopyran-3-carbonitriles are active against tumor cell lines (Huh7, Caco 2, HCT 116) or protein kinases (CLK1).

Keywords: microwave / chromeno[2,3-d]pyrimidine / benzopyran-2-yl methanimidate/ formamidine.