1099104-77-4Relevant academic research and scientific papers
Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue
Popowycz, Florence,Fournet, Guy,Schneider, Cédric,Bettayeb, Karima,Ferandin, Yoan,Lamigeon, Cyrile,Tirado, Oscar M.,Mateo-Lozano, Silvia,Notario, Vicente,Colas, Pierre,Bernard, Philippe,Meijer, Laurent,Joseph, Beno?t
experimental part, p. 655 - 663 (2009/12/01)
Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1- f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.
