Synthesis of novel spiro[pyrazolo[4,3-d]pyrimidinones and spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3'-indoline]-2',4(3H)-diones and their evaluation for anticancer activity

Abstract

An efficient and novel method for the preparation of spiro[pyrazolo[4,3-d]pyrimidin]-7'(1'H)-ones by the condensation of 4-amino-1-methyl-3-propylpyrazole-5-carboxamide with ketones under mild conditions using catalytic InCl₃ was reported. This method has been extended for the synthesis of novel spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3'-indoline]-2',4(3H)-dione which are having potential applications in medicinal chemistry. All the synthesized compounds were evaluated for their anti-proliferative properties in vitro against cancer cell lines and several compounds were found to be active. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.

Keywords: 4-Amino-1-methyl-3-propylpyrazole-5-carboxamide; Anticancer agents; InCl(3); Spiro[benzo[4,5]thieno[2,3-d]pyrimidine-2,3′-indoline]-2′,4(3H)-dione; Spiro[pyrazolo[4,3-d]pyrimidin]-7′(1′H)-ones.