Nucleoside analogues. 9. Seco-nucleoside analogues of some 5-fluorouracil/nitrosourea molecular combinations having uracil as base: synthesis and anti-tumour activity
Mcelhinney, R.S.; Mccormick, J.E.; Bibby, M.C.; Double, J.A.; Atassi, G.; Dumont, P.; Pratesi, G.; Radacic, M.
Anti-Cancer Drug Design 4(3): 191-207
1989
ISSN/ISBN: 0266-9536 PMID: 2803467 Document Number: 339338
The synthesis of representative seco-nucleoside analogues of 5-fluorouracil (5-FU)/nitrosourea molecular combinations having uracil (U) as base instead of 5-FU is described. The anti-tumour activity of corresponding pairs of drugs is compared in experimental tumours of the mouse colon, lung and breast. These studies have demonstrated that the presence of a hydrogen or fluorine atom at pyrimidine C-5 is unimportant for the activity shown against most of the experimental tumours employed, rather that the pyrimidine cyclic urea and/or alkylthio functionalities may constitute the critical factors. One exception is the prototypical compound B.3839 and its U analogue B.3912. B.3839 is highly active against colon 38 adenocarcinoma, a tumour which is highly responsive to 5-FU, whereas most of the activity is lost in B.3912. The 5-FU release profile of some of these molecular combinations could be adequate or effective in treatment of slow-growing clinical tumours.