1.
Bioorg Med Chem Lett
; 22(7): 2609-12, 2012 Apr 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22374217
RESUMO
Pyridyl aminothiazoles comprise a novel class of ATP-competitive Chk1 inhibitors with excellent inhibitory potential. Modification of the core with ethylenediamine amides provides compounds with low picomolar potency and very high residence times. Investigation of binding parameters of such compounds using X-ray crystallography and molecular dynamics simulations revealed multiple hydrogen bonds to the enzyme backbone as well as stabilization of the conserved water molecules network in the hydrophobic binding region.