Design, Synthesis, and Antitumor Evaluation of Novel Pyrazolo[3,4-d]pyrimidine Derivatives

Abstract

A new series of pyrazolo[3,4-d]pyrimidines has been synthesized. The new compounds were tested for their antitumor activity on 60 different cell lines, and some of the compounds were found to have potent antitumor activity. In particular, 2-hydroxybenzaldehyde [1-(4-chlorophenyl)-3-methyl-1H-pyrazolo-[3,4-d]pyrimidin-4-yl]hydrazone (VIIa) was found to be the most effective among the other derivatives, showing IC50 values of 0.326 to 4.31 μM on 57 different cell lines.

Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-d]pyrimidine derivatives as anti-cancer agents

“…31 Cyclization of compound VIII was afforded via its reux with formamide to yield 1-phenyl-1,5dihydro-4H-pyrazolo [3,4-d]pyrimidin-4-one IX. 32 Aer that chlorination of compound IX was carried out by reux in POCl 3 followed by a coupling reaction with excess anhydrous piperazine (ratio 1 : 10) in isopropanol to obtain the key intermediate XI. 33 In Scheme 2, the starting intermediates IIa-f, III, IV & V were prepared via the reaction of chloroacetyl chloride (I) with aniline derivatives to give IIa-f. [34][35][36] Similarly, precursor III was prepared by reacting chloroacetyl chloride with a-naphthol.…”

Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

“…Kandeel et al [ 116 ] synthesized pyrazolo[3,4- d ]pyrimidin-4(5 H )-one 152 via the reaction of 5-amino-3-methyl-1 H -phenylpyrazole-4-carbonitrile 65 with formic acid ( Scheme 78 ) [ 116 ].…”

Synthesis, Characterization and <i>In Vitro</i> Antitumor Evaluation of New Pyrazolo[3,4-d]Pyrimidine Derivatives

“…Pyrazolo [3,4-d]pyrimidine nucleus is the bioisostere of purine [4] [5], which exhibits promising activity as antitumor by competitive inhibition for ATP kinase enzymes. Many pyrazolo [3,4-d]pyrimidine derivatives were reported as antitumor agents [6] [7] [8]. The cytotoxic activity of such compound may attribute to inhibition of several enzymes such as tyrosine kinase [9], Src kinase [10], cyclin dependent kinase (CDK) [11], mammalian target of rapamycin (mTOR) [12] and glycogen synthase kinase (GSK) [13] [14].…”