5,5-Disubstituted barbituric acids and their analogues

Abstract

Condensation of 2-substituted triethyl esters of 2-carboxy-1,7-heptanedioic acids XIV - XIX with urea afforded 5-substituted 5-(4-carboxybutyl)barbituric acids I - VI. Similarly, thiourea and the triethyl esters XIV and/or XVI gave the analogous 5-substituted 5-(4-carboxybutyl)-2-thiobarbituric acids, VII and VIII respectively. Condensation of guanidine with triethyl esters XIX - XXI produced 5-substituted derivatives of 5-(4-carboxybutyl)-2-amino-1,4,5,6-tetrahydro-4,6-dioxopyrimidine, IX -XI. Reactions of the acids II and IV with glycine ethyl ester, using the method of mixed anhydrides, gave rise to ethoxycarbonylmethylamides, XII and XIII respectively. Some of the compounds prepared exhibited enhancing effects on 5-fluorouracil in curing leukemic mice, and antineoplastic activity, manifesting itself by reducing the size of transplanted tumours in experimental animals.