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

  • Bioorg Med Chem Lett. 2017 Mar 15;27(6):1446-1450. doi: 10.1016/j.bmcl.2017.01.088.
Ismail  1 ,  Bhaskar Kuthati  1 ,  Gangadhar Thalari  1 ,  Venkatesham Bommarapu  2 ,  Chaitanya Mulakayala  3 ,  Suresh Kumar Chitta  3 ,  Naveen Mulakayala  4
Affiliations
  • 1. Department of Chemistry, Osmania University, Hyderabad 500046, India.
  • 2. DR Reddy's Institute of Lifesciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India.
  • 3. Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515001, India.
  • 4. DR Reddy's Institute of Lifesciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India. Electronic address: [email protected].
PMID: 28216402 DOI: 10.1016/j.bmcl.2017.01.088
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.