Uses of cyclohexan‐1,3‐dione for the synthesis of tetrahydrochromeno[3,4‐c]chromen derivatives with anti‐tumor activities

Abstract

Cyclohexan‐1,3‐dione (1) was used as the key starting material, which reacted with salicylaldehyde (2) and either malononitrile (3a) or ethyl cyanoacetate (3b) in ethanol containing a catalytic amount of triethylamine to give the 3,4,7,12b‐tetrahydrochromeno[3,4‐c]chromen‐1‐one derivatives 5a,b. The latter compounds underwent Gewald's thiophene synthesis through the reaction with either malononitrile or ethyl cyanoacetate to give compounds 6a‐d, respectively. On the other hand, compound 5a was used for the synthesis of annulated chromeno[3,4‐c]chromen derivatives through its reaction with different chemical reagents. The synthesized compounds were evaluated against the six cancer cell lines A549, HT‐29, MKN‐45, U87MG, SMMC‐7721, and H460 using the standard MTT assay in vitro, with foretinib as the positive control, many compounds expressed high inhibitions. The most active compounds 5b, 6b, 6d, 7, 9b, 11a, 11b, 13, 17, 18b, 20b, 21b, 21e, and 21f were selected for inhibition of five tyrosine kinases and some selected compounds for Pim‐1 kinase inhibition. The results showed that compounds 6b, 6d, 11a, 13, 17, 20b, and 21e were the most potent compounds with the tyrosine kinases and compounds 6d, 11a, 20b, and 21e were the most potent inhibitors of Pim‐1 kinase.

Antiproliferative and Antiprostate Cancer Activities of Heterocyclic Compounds Derived from Cyclohexane-1,4-dione

“…In addition to the presence of three singlet (D 2 O exchangeable) at δ 3.37, 8.13 and 9.93 ppm for NH 2 and two NH groups, respectively. The 13 Continuing our previous work on the synthesis of thiophene or thiazole derivatives using phenyl isothiocyanate in basic dimethylformamide and subsequent heterocyclization of the intermediate potassium salt by a-haloketones, 47,48 in this work we have demonstrated such reactions with the aim of preparing heterocyclic compounds with predicted biological activity. For example, the reaction of compound 3 with phenyl isothiocyanate and potassium hydroxide in dimethylformamide gave the potassium salt intermediate 17, followed by the addition of a-chloro-…”

Design, Synthesis, Molecular Docking and Biological Studies of 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives and Their Uses in Heterocyclic Synthesis

“…Nitrogen containing heterocyclic organic compounds having extra keto group show interesting chemical properties as well as biological activity. The reaction of anthranilic acid (1) [17] using anthranilic acid and some acid chlorides where the reaction took place in two steps. First the amide formation in dimethylformamide solution followed by the second step of the ring closure that was carried out in glacial acetic acid solution.…”

“…In this work, recently, our research group were involved through the studying reactions of cyanomethylene reagents. [14][15][16][17] As a continuation of this program we report the use of 2-(4-oxo-4H-benzo[d] [1,3]oxazin-2-yl)acetonitrile in the synthesis of biologically active heterocyclic derivatives followed by further heterocyclization of the products to afford biologically active fused derivatives.…”

“…Moreover, information's provided by the material safety data sheet of the substance formaldehyde also showed the substance to be carcinogenic and possess serious health effects. In this work, recently, our research group were involved through the studying reactions of cyanomethylene reagents [14–17] . As a continuation of this program we report the use of 2‐(4‐oxo‐4 H ‐benzo[ d ][1,3]oxazin‐2‐yl)acetonitrile in the synthesis of biologically active heterocyclic derivatives followed by further heterocyclization of the products to afford biologically active fused derivatives.…”

Heterocyclic compounds derived from cyclohexane-1,4-dione: synthesis of tetrahydro-4H-chromene and tetrahydrobenzo[d]thiazole derivatives as target SARS-CoV-2 main protease (Mpro) and potential anti-Covid-19

“…In the past several years, the development of new multi-component domino reactions has become an active and challenging topic in modern organic chemistry [ 24 ]; they can readily provide greater atom-economic access to a diverse spectrum of compounds and their libraries for screening. Recently, our research group was involved through the studying the multi-component reactions of cyclohexan-diones [ 25 – 28 ]. As a continuation of this program we are presenting in this work the multi-component reaction of cyclohexan-1,4-dione [ 29 , 30 ] followed by further heterocyclization of the products to afford biologically active fused derivatives.…”