Synthesis of New N,N'-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

Abstract

New N,N’-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3α/β, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC50 = 0.041 μM).

5-Ene-4-thiazolidinones – An efficient tool in medicinal chemistry

“…Modifying the imidazolidine derivatives the new cell division cycle 7 kinase inhibitors were designed 135 and (Z)-2-(benzylamino)-5-(1H-pyrolo2,3-b]pyridin-3-ylmethylene)-1,3thiazol-4(5H)-one] was selected as a lead compound [332] (Scheme 68). 2-N,N 0 -Disubstituted diamines bearing 5-arylidene-4thiazolidinone moiety 136 (Scheme 69) had shown nanomolar inhibition potency (IC 50 40 nM) towards tyrosine phosphorylationregulated kinases 1A [333]. This result prompted to explore the symmetric 1,2-diamino-linker grafted on N-3 position of two different 5-arylidenerhodanine platforms in order to modulate potential biological activity and led to the synthesis of unsymmetrical linked bis-5-arylidenerhodanine derivatives with anticancer effects [334].…”

Prospective study directed to the synthesis of unsymmetrical linked bis-5-arylidene rhodanine derivatives via “one-pot two steps” reactions under microwave irradiation with their antitumor activity

“…Starting from 1,4-bis(3-aminopropyl)piperazine, this strategy was also extended to the synthetic preparation of symmetric N,N'-disubstituted diamines bearing 5-arylidene-1,3-thiazolidine-4-one moiety and to our surprise one of these compounds has shown nanomolar inhibition potency (IC 50 40 nM) towards DYRK1A ( Fig. 1) (Coulibaly et al, 2012b). This result prompted us to explore now the use of symmetric 1,2-diamino linker grafted on N-3 position of two different 5-arylidene rhodanine platforms in order to modulate potential biological activities.…”

Synthesis and Cytotoxic Activity against K562 and MCF7 Cell Lines of SomeN-(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)thio)acetamide Compounds

“…e 5-arylidene-2-thioxothiazolidine-4-one derivatives have been shown to inhibit aldose reductase [21][22][23][24], hepatitis C virus (HCV) [25,26], human immunodeficiency virus (HIV) [27][28][29], JNK-stimulating phosphatase-1 (JSP-1) [30], glycogen synthase kinase-3 (GSK-3) [31,32], 17βhydroxysteroid dehydrogenase type 3 [33], and histone acetyltransferases (HATs) [34]. Specifically, the 5-arylidene-2-thioxothiazolidine-4-one moiety is reported to possess anticonvulsant [35], antimicrobial [36], antidiabetic [37], antitumor [38][39][40], and anticancer activities [41][42][43][44]. e aforementioned compounds have inspired the idea of synthesizing hybrid derivatives where moieties of quinazolin-4-one and 2-thioxothiazolidin-4-one could be incorporated with each other to be an organic molecule with more effective anticancer activity.…”