A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line

Tan Uygun M., Amudi K., Doğan Turaçlı İ., Mengeş N.

MOLECULAR DIVERSITY, vol.26, no.1, pp.113-124, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1007/s11030-020-10161-8
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.113-124
  • Keywords: Alkyne cyclization, Allene, Pyrazole, Lung adenocarcinoma, KRAS mutant lung cancer, ADMET, DESIGN, INHIBITORS
  • Van Yüzüncü Yıl University Affiliated: Yes


Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160 mu M concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure-activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable.