demonstrated that 4-aminopyra-I zolo [3,4-d]pyrimidine (4-APP) and various congeners1923 are active against a variety of transplantable animal tumors.15~ 22, 26-29, 3 2 ~3 3 In most of these studies, treatment was initiated shortly after implantation of the tumor,22. 26-29, 32, 33 and with the exception of lymphoid leukemia L1210 and leukemia L5178 studies,220 29 alteration in local tumor size rather than prolongation of life was generally employed as the criterion of drug effectiveness. I n addition, ~-A P P has been shown to be approximately 33% as effective as amethopterin in increasing the survival time of mice with systemic lymphoid leukemia Ll2lO.15 T h e observations by Skipper et a1.26 that 6-mercaptopurine-resistant variants of adenocarcinoma 755 and leukemia L1210 displayed sensitivity to treatment with ~A P P were of particular interest in view of the structurally isomeric relationship between 4-APP and adenine.
4 -A P P
A D E N 1 N E I t is the purpose of the present study, employing survival time as the principal criterion of therapeutic activity, to (1) determine the relative effectiveness of 4-APP and certain of its derivatives against advanced systemic leukemia L1210 in mice; (2) determine the effectiveness of ~A P P against a subline of L1210 resistant to both 8-azaguanine and 6-mercaptopurine; and (3) investigate the effectiveness of 4-substituted pyrazolo[3,4-d]pyrimidines against adenocarcinoma 755 and sarcoma 37.