2. Academic Validation
  3. Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents

Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents

  • Bioorg Med Chem Lett. 2016 Nov 1;26(21):5203-5206. doi: 10.1016/j.bmcl.2016.09.062.
N Ravi Kumar 1,  Y Poornachandra 2,  D Krishna Swaroop 1,  G Jitender Dev 1,  C Ganesh Kumar 2,  B Narsaiah 3
Affiliations

Affiliations

  • 1 Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
  • 2 Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
  • 3 Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: narsaiah@iict.res.in.
PMID: 27720296 DOI: 10.1016/j.bmcl.2016.09.062
Abstract

A series of novel pyrido[2',3':3,4] pyrazolo[1,5-a]pyrimidine derivatives 6-9 were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 5 on reaction with symmetrical and unsymmetrical aliphatic and aromatic 1,3-diketones/α,β unsaturated ketones/α,β unsaturated keto ethers under conventional method. All the final compounds 6a-c, 8a-b and 9a-l were screened for Anticancer activity against five human Cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2 (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a, 9f and 9k which showed promising Anticancer activity have been identified. Further, the promising compounds (8a and 9f) were able to inhibit the human Topoisomerase I (TopI) activity similar to that of camptothecin.

Keywords

1,3 diketones; Anticancer activity; Pyrazolo[3,4-b]pyridine; Pyrimidine; α,β unsaturated ketones.

Figures