6 '-chloro-7- or 9-(2,3-dihydro-5H-4,1-benzoxathiepin-3-yl)-7H- or 9H-purines and their corresponding sulfones as a new family of cytotoxic drugs

A series of 1-(2,3-dihydro-5H-4,1-benzoxathiepin-3-yl)pyrimidine derivatives were synthesized and two of them (8 and 9) showed a modest antiproliferative activity against the MCF-7 breast cancer cell line. We then decided to change the pyrimidine base for the more lipophilic 6'-chloropurine, and the N-9'purine (15) and N-7' purine (17) were obtained. The sulfone N-7'-alkylated-6-chloropurine 18 was the most active derivative. Compound 17 was found to be slightly more active than its regioisomer 15, with an activity similar to that of 5-fluorouracil as a reference drug. Encouraged by these values, we tested these compounds against both the HT-29 human colon cancer cell line and the IEC-6 normal rat intestinal epithelial cell line, and 15 was found to be 12.7-fold more active against HT-29 than versus IEC-6. (c) 2006 Elsevier Ltd. All rights reserved.