Antimicrob Agents Chemother 53:5046–5054PubMedCrossRef”
“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 SAR302503 molecular weight activity (CXCR2-receptor antagonists) (Walters et al., 2008), inhibit the growth of HCMV-human cytomegalovirus (Revankar et al., 1998), and be corticotrophin-releasing hormone (CRH-R1) receptor antagonists (display antidepressant activity) (Beck et al., 1999). In this study, in continuation of our work on thiazolo[4,5-d]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 STA-9090 order Wagner, 2008). Entinostat 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-diaryl-2-thioxo-5,6-dihydro-4H-thiazolo[4,5-d]pyrimidin-7-ones (2) and 7-chloro-3,5-diaryl-thiazolo[4,5-d]pyrimidine-2-thiones (3) with diethyl sulfate and water for the replacement of the 2-thioxo group by an oxygen else function (Scheme 1). Compounds 2 and 3 were obtained from 4-amino-5-carboxamido-3-substituted-2,3-dihydrothiazole-2-thiones (1) (Gewald, 1966) according to a reported earlier procedure (Becan and Wagner, 2008). Pyrimidine ring formation with appropriate aryl aldehyde, followed by chlorination provided the desired cores 2 and 3, bearing the respective aromatic substituent at position 3 and 5, which could further be treated with diethyl sulfate and hydrolyzed to yield 2-thiazolones 4a–4f and 5a–5f. All synthesized compounds were submitted to the National Cancer Institute (NCI, Bethesda, Maryland) to evaluate their growth inhibitory effects on 60 human cancer cell lines, derived from nine neoplasmatic diseases. Five derivatives 4a, 4b, 5a, 5b, and 5d were selected for a primary in vitro antitumor assay, at 10−5 M concentration. Results were expressed as percent growth of the treated cells, compound 5a showing mean percent growth =71.26 was further tested at five different concentrations. Fig.