Synthesis and anticancer evaluation of novel 3,5-diaryl-thiazolo[4,5- d ]pyrimidin-2-one derivatives
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Med Chem Res DOI 10.1007/s00044-012-0231-7
ORIGINAL RESEARCH
Synthesis and anticancer evaluation of novel 3,5-diaryl-thiazolo[4,5-d]pyrimidin-2-one derivatives Lilianna Becan • Edwin Wagner
Received: 24 January 2012 / Accepted: 11 September 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract The 2-oxo analogs of thiazolo[4,5-d]pyrimidine-2-thiones were prepared to study their cytotoxic activity. Five of the newly synthesized compounds were selected by the National Cancer Institute (Bethesda, MD, USA) for a primary in vitro antitumor assay. 7-Chloro-3,5diphenyl-thiazolo[4,5-d]pyrimidin-2-one (5a) proved to be the most active one among the screened derivatives and was further evaluated in the full panel of 60 cell lines at five different concentrations. The structures of compounds were determined by IR, 1H-NMR, 13C-NMR, X-ray, and elemental analysis. Keywords Antitumor agents In vitro studies Thiazolo[4,5-d]pyrimidin-2-ones Synthesis
Introduction Thiazolo[4,5-d]pyrimidines, 7-thio analogs of purines are potentially bioactive molecules. In contrast with related 2-thioxo-thiazolo[4,5-d]pyrimidine derivatives, the 2-oxo analogs have not been very well explored in medicinal chemistry. The synthesis and biological evaluation of the substituted 2-oxo-thiazolo[4,5-d]pyrimidines have been the subject of several review articles. They were reported to possess antibacterial, antifungal (Akbari et al., 2008; Habib et al., 2007), and anti-inflammatory activity (CXCR2receptor antagonists) (Walters et al., 2008), inhibit the growth of HCMV-human cytomegalovirus (Revankar et al., 1998), and be corticotrophin-releasing hormone (CRH-R1) L. Becan (&) E. Wagner Department of Drugs Technology, Wroclaw Medical University, Pl. Nankiera 1, 50-140 Wroclaw, Poland e-mail: [email protected]
receptor antagonists (display antidepressant activity) (Beck et al., 1999). In this study, in continuation of our work on thiazolo[4,5d]pyrimidine derivatives, the synthesis and in vitro cytotoxic evaluation of thiazolo[4,5-d]pyrimidin-2-ones are reported. These designed thiazolo[4,5-d]pyrimidine-2-ones are related to thiazolo[4,5-d]pyrimidine-2-thiones that have been previously reported to be potent antitumor agents (Becan and Wagner, 2008). Thiazolo[4,5-d]pyrimidine derivatives have been extensively studied as potential drug candidates and also have anticancer activity (Rida et al., 1996; Fahmy et al., 2002, 2003). Most of these compounds provided with anticancer activity possess an aromatic rings and electronegative substituent directly linked to the C-17 of the essential core (Fig. 1) or attached at aromatic moieties. The method involved subsequent treatment of the appropriate 3,5-diaryl2-thioxo-5,6-dihydro-4H-thiazolo[4,5-d]pyrimidin-7-ones (2) and 7-chloro-3,5-diaryl-thiazolo[4,5-d]pyrimidine-2thiones (3) with diethyl sulfate and water for the replacement of the 2-thioxo group by an oxygen function (Scheme 1). Compounds 2 and 3 were obtained from 4-amino-5-carboxamido-3-substituted-2,3-dihydr
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