(5b), as examples, were tested on different cancer cell lines including HeLa, MCF-7, and HepG2. Malignant cells were cultured in DMEM medium and incubated with different concentrations of the titled compounds. Cell viability was quantitated by MTT assay.

The reaction of 2‐amino‐4,5‐dimethyl‐ thiophene‐3‐carboxamide with iso(and isothio) cyanates for the synthesis of thieno[2,3‐d]pyrimidines has been investigated. The reactions under microwave irradiation in the presence of N,N‐dimethyl acetamide as solvent gave 5,6‐dimethylthieno[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione, 5,6‐dimethyl‐2‐thioxo‐2,3‐dihy‐ drothieno[2,3‐d]pyrimidin‐4(1H)‐one, and 2‐aryla‐ mino‐5,6‐dimethylthieno[2,3‐d]pyrimidin‐4(3H)‐one derivatives. These reactions probably proceed through intermediates 4,5‐dimethyl‐2‐substitutedcarbamoth‐ ioylaminothiophene‐3‐carboxamides. Two of these intermediates were isolated. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:346–349, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20557

In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.

The synthesis of new derivatives of 3-phenyl-1,5-dimethyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazines 5a-e and 7a-e is described through heterocyclisation of hydrazino derivative (3) with aromatic aldehydes or carbon disulfide and alkyl halides. [(1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl) sul fanyl]methyl cyanide was singled out to be tested on different cancer cell lines including HeLa, MCF-7, and HepG2. Malignant cells were cultured in DMEM medium and incubated with different concentrations of the titled compounds. Cell viability was quantified by MTT assay.