The synthesis and biological activity of a series of 2,4-diaminopyrido[2,3-D] pyrimidine based antifolates as antineoplastic and antiarthritic agents

A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 we re synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6-ethyny lpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the ac tivated 1,2,4-triazole intermediate 6. Compound 7 was used as the key inter mediate for the preparation of the final products. The detailed biological evaluation of these compounds both as antineoplastic and antiarthritic agen ts will be discussed. (C) 1998 Elsevier Science Ltd. All rights reserved.