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Eur J Med Chem. 2013;70:447-55. doi: 10.1016/j.ejmech.2013.08.052. Epub 2013 Sep 15.

Synthesis, structure-activity relationship and biological evaluation of 2,4,5-trisubstituted pyrimidine CDK inhibitors as potential anti-tumour agents.

Author information

1
School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.

Abstract

A series of 2,4,5-trisubstituted pyrimidines have been synthesised and characterised, which exhibited potent CDK inhibition and anti-proliferative activities. The structure-activity relationship is analysed and a rational for CDK9 selectivity is discussed. Compound 9s, possessing appreciable selectivity for CDK9 over other CDKs, is capable of activating caspase 3, reducing the level of Mcl-1 anti-apoptotic protein, and inducing cancer cell apoptosis.

KEYWORDS:

Anti-cancer drug discovery; CDK9 inhibitors; Inhibitor design; Mcl-1 anti-apoptotic proteins; RNA polymerase II

PMID:
24185375
DOI:
10.1016/j.ejmech.2013.08.052
[Indexed for MEDLINE]

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