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Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation
Author(s) -
Vekariya Mayur K.,
Vekariya Rajesh H.,
Brahmkshatriya Pathik S.,
Shah Nisha K.
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13334
Subject(s) - pyrazole , pyrimidine , chemistry , selectivity , kinase , cyclin dependent kinase , cyclin dependent kinase 2 , combinatorial chemistry , enzyme , docking (animal) , ic50 , stereochemistry , biochemistry , protein kinase a , in vitro , cell cycle , cell , medicine , nursing , catalysis
A series of new pyrimidine‐pyrazole hybrid molecules were designed as inhibitors of cyclin‐dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2‐CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC 50 < 20 n m ); which can be further optimized to have selectivity over other kinase isoforms.