As part of our program to identify novel cytotoxic agents, various series of hexahydrocycloocta [4,5]thieno [2,3-d] pyrimidines and pyrimidin-4-ones substituted by aryl at the C-2 position together with phenylethylamino, substituted amino, hydrazinyl or arylidenhydrazinyl substituents at the C-4 position were synthesised. These compounds were prepared as bioisosteres of gefitinib, an antitumour drug used for the treatment of gastrointestinal stromal tumours. All compounds exhibited antitumour activity against (HCT 116) cell line in vitro. Eight compounds (IC 50 : 3.89, 4.65, 6.63, 6.94, 7.89, 9.53,12.00 and 12.30 µg mL −1 , respectively) exhibited 4.3 to 1.3 fold more potent antitumour activity than imatinib (IC 50 : 16.93 µg mL −1 ). Also, a docking study of the newly synthesised compounds with the active site of CDK2 was described.

VIIIb) exhibit significant cytotoxicity against the human colon carcinoma cell line HCT 116 and are more potent than imatinib. -(KANDEEL, M. M.; MOUNIR, A. A.; REFAAT*, H. M.; KASSAB, A. E.; J. Chem. Res. 36 (2012) 5, 266-275, http://dx.doi.org/10.3184/174751912x13333849411283 ; Dep. Org. Chem., Fac. Pharm., Cairo Univ., Kasr El-Aini 11562, Cairo, Egypt; Eng.) -K. Woydowski 42-171

Synthesis of Thieno[2,3-d]pyrimidines, Thieno[2,3-d]triazinones and Thieno[2,3-e]diazepinones of Anticipated AnticancerActivity. -A variety of hitherto unknown title heterocycles fused to cyclooctane is synthesized and evaluated for their anticancer activities. Almost all the compounds show significant activities. Some of them, i.e. derivatives (III), (V), (VII), (XIIb) and (XIVa) display higher antitumor activity than the reference imatinib. -(KANDEEL, M. M.; MOUNIR, A. A.; REFAAT*, H. M.; KASSAB, A. E.; J. Chem. Res. 36 (2012) 2, 105-110, http://dx.doi.org/10.3184/174751912x13282020691270 ; Dep. Org. Chem., Fac. Pharm., Cairo Univ., Cairo, Egypt; Eng.) -A. Forchert 30-191

A novel series of 4-aminohexahydrocycloocta [4,5]thieno [2,3-d]pyrimidines, hexahydrocycloocta[4,5]thieno[2,3-d]-1,2,3-triazin-4-one and its N-3 substituted derivatives in addition to 3-aryl hexahydrocycloocta [4,5] thieno[2,3-e]-1,4-diazepin-5-ones were synthesised. Also, 2-(N-ethylcarbamothioylamino) hexahydrocycloocta[b] thiophene-3carbonitrile and 19-imino tetradecahydrocycloocta[4΄,5΄] thieno[2΄,3΄:4,5]pyrimido[1,6-a] cycloocta[4,5]thieno [3,2-e]pyrimidine-9-thione were prepared. Almost all the synthesised compounds exhibited anti-tumour activity against human colon carcinoma (HCT 116) cell line in vitro. Five compounds (IC 50 : 15.92, 22.59, 25.85, 27.40 and 29.70 µM, respectively) exhibited 2.16 to 1.15 fold more potent antitumour activity than imatinib (IC 50 : 34.40 µM).