Nucleoside analogues. 9. Seco-nucleoside analogues of some 5-fluorouracil/nitrosourea molecular combinations having uracil as base: synthesis and anti-tumour activity.
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.
McElhinney
R S
RS
Laboratory of the Medical Research Council of Ireland, Trinity College, Dublin.
McCormick
J E
JE
Bibby
M C
MC
Double
J A
JA
Atassi
G
G
Dumont
P
P
Pratesi
G
G
Radacic
M
M
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy; D005472:Fluorouracil; D008175:Lung Neoplasms / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000627:therapeutic use; D009705:Nucleosides; D012995:Solubility; D014498:Uracil
D000964:Antimetabolites, Antineoplastic; D009607:Nitrosourea Compounds; D009705:Nucleosides; D014498:Uracil; D005472:Fluorouracil