Microwave assisted practical synthesis of 4-imino-3-phenyl-3,4-dihydro-1H-chromeno[2,3-d]pyrimidine-2(5H)-thione derivatives and exploration of their biological activities

Ali Bouattour,Jean-Pierre Bazureau,Anne Corlu,Mehdi Fakhfakh,Houcine Ammar,Souhir Abid,Rémy Le Guével,Stéphane Bach,Ludovic Paquin,Sandrine Ruchaud

doi:10.24820/ark.5550190.p010.040

Abstract

The synthesis of a series of new 4-imino-3,4-dihydro-1H-chromeno[2,3-d]pyrimidine-2(5H)-thiones 6(a-f) without substituent in C-5 position using microwave dielectric heating is reported. These new compounds were obtained in three steps with good overall yields (21-50%). _figure presented_. ©ARKAT USA, Inc.

Highlights

The interest for 4H-chromenes and their derivatives increased since the two last decades because this class of compounds are components of many naturally occurring products and have been subjected to structural modifications for potential medicinal properties
We studied the chemical reactivity of the 2-amino group of chromene-3-carbonitrile with aryl isothiocyanate under microwave dielectric heating in order to produce novel 4-imino-3,4-dihydro-1H-chromene[2,3-d]pyrimidine
Owing to that our synthetic strategy involved the preparation of iminocoumarin-3-carbonitriles 3 as starting materials, we selected a series of aromatic aldehydes 1(a-f) bearing diethylamino- or methoxy- groups at various positions for the introduction of molecular diversity on the expected compounds

Summary

Introduction

The interest for 4H-chromenes and their derivatives increased since the two last decades because this class of compounds are components of many naturally occurring products and have been subjected to structural modifications for potential medicinal properties. As examples (Figure 1), the racemic 15-(3-methoxyphenyl)9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-14-imine (I) was identified as novel inhibitor of acetylcholine esterase (hAChE IC50 58 nM) and butyrylcholine esterase (hBuChe IC50 302 nM) with a selectivity of 5.2. This compound presented very weak activity in Aβ1-42 aggregation for Alzheimer's disease therapy. It is noteworthy that the antitubercular (Mycobacterium tuberculosis) and antimicrobial (Gram-positive and Gramnegative bacterial species) activities of these compounds have been investigated In this context, we decided to develop a series of 2-amino-4H-[1]chromene-3-carbonitrile without substituent in C-4 position via the 3-cyanoiminocoumarin route.. 2(5H)-thione derivatives (Figure 1) and to evaluate their impact respectively on protein kinase activity and antiproliferative activity with representative tumoral cell lines for possible detection of biological properties

Results and Discussion

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Conclusions