186692-41-1Relevant articles and documents
Synthesis and biological evaluation of seliciclib derivatives as potent and selective CDK9 inhibitors for prostate cancer therapy
Alsfouk, Aisha A.,Alshibl, Hanan M.,Altwaijry, Najla A.,Alsfouk, Bshra A.,Al-Abdullah, Ebtehal S.
, p. 109 - 120 (2021)
Seliciclib is a cyclin-dependent kinase (CDK) inhibitor that has been assayed in phase II clinical trials as an anticancer agent. This paper describes the synthesis of novel derivatives of seliciclib with improved potency, metabolic stability, aqueous solubility, and anti-proliferative activity. The new derivatives showed a novel CDKs selectivity profile. Replacement of ethyl alcohol at position 2 of purine with dimethylaminopropyl and fluorination of benzyl at position 6 of purine of seliciclib resulted in the formation of a derivative that potently and selectively inhibited CDK9 (26?nM vs. CDK9 and > 60-fold selectivity vs. CDK2/5/7). In comparison to seliciclib, this derivative shows lower metabolic clearance (25% lower in Clint), higher aqueous solubility and is more cytotoxic in androgen-independent prostate cancer cells. Graphic abstract: [Figure not available: see fulltext.].
Synthesis and pharmacophore modelling of 2,6,9-trisubstituted purine derivatives and their potential role as apoptosis-inducing agents in cancer cell lines
Calderón-Arancibia, Jeannette,Espinosa-Bustos, Christian,Ca?ete-Molina, álvaro,Tapia, Ricardo A.,Faúndez, Mario,Torres, Maria Jose,Aguirre, Adam,Paulino, Margot,Salas, Cristian O.
, p. 6808 - 6826 (2015/05/06)
Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.
Practical synthesis of roscovitine and CR8
Oumata, Nassima,Ferandin, Yoan,Meijer, Laurent,Galons, Herve
experimental part, p. 641 - 644 (2010/04/22)
Roscovitine and CR8 are potent inhibitors of cyclin-dependent kinases. A scalable synthesis of both inhibitors is described. In the case of CR8, the biarylmethylamine moiety was obtained as a stable and high-purity salt.
