Pyrazolopyrimidine nucleosides. 12. Synthesis and biological activity of certain pyrazolo[3,4-d]pyrimidine nucleosides related to adenosine

Abstract

The chemical synthesis of certain 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides is described. Using 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (1) as the starting material, the reactive intermediate 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (2) was prepared in excellent yield. Compound 2 served as a versatile precursor for the synthesis of a number of 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides. In antitumor studies of these nucleosides, in vitro and in vivo, it was found that any alteration of the 4-amino substituent of 4-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (3) was accompanied by a significant decrease or loss of antitumor activity. On the other hand, introduction of certain substituents at the 3 position of 3 (synthesis reported previously) led to a dramatic increase in antitumor activity in comparison to the parent compound.

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline

“…Pyrazolopyrimidine derivatives constitute an interesting class of heterocycles because of their synthetic versatility, effective biological activities, and pharmacological importance as purine analogs [1][2][3][4][5]. Various related compounds of pyrazolopyrimidines have antitumor and antileukemic activities [6,7].…”

Synthesis of New Pyrazolo [5, 1-c] [1, 2, 4] triazines from 5-Aminopyrazole and Study Biological Activity and Cytotoxicity

“…5-Aminopyrazoles have gained significant interest for synthetic organic chemists in the development of new biological active molecules of the pharmacological importance [1][2][3][4][5]. They have been used in the preparation of polyfunctionalized heterocyclic compounds such as pyrazolopyrimidines and pyrazolotriazines [6][7][8][9].…”

Catalytic synthesis of 6-aryl-1H-pyrazolo[3,4-d]pyrimidin-4[5H]-ones by heteropolyacid: H14[NaP5W30O110] and H3PW12O40

“…Pyrazolo [3,4-d]pyrimidines are of considerable chemical and pharmacological importance as purine analogues [1][2][3]. Various compounds with related structures also passes antitumor and anti-leukemia activities [4,5].…”