Structure-activity relationships observed on screening a series of pyrazolopyrimidines against experimental neoplasms.

Abstract

Summary A large number of pyrazolopyrimidines have been screened for anticancer activity against neoplasms susceptible to inhibition by purine antagonists (Adenocarcinoma 755 and Leukemia 5178). Of the compounds studied, consistent and significant activity appears to be limited to the 4-amino-, the 4-monoalkylamino-, and 4-dialkylaminopyrazolo(3,4- d )pyrimidines, and the 1-alkyl derivatives of these compounds. With respect to the analogs of 4-aminopyrazolo(3,4- d )pyrimidine, an adenine isomer, a clearly defined structure-activity relationship has been observed. The inhibition of L. arabinosus by 4-APP can be prevented by purines and purine derivatives. Strains of L. arabinosus resistant to A-methopterin or to certain purine antagonists were not significantly cross-resistant to 4-APP. A 6-mercaptopurine-resistant line of Adenocarcinoma 755 has been selected. This resistant tumor does not appear to be cross-resistant to 4-APP.