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Chemical Structure| 1805434-14-3 Chemical Structure| 1805434-14-3

Structure of 1805434-14-3

Chemical Structure| 1805434-14-3

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Nicholas O. Schneider ; Kendra Gilreath ; Daniel J. Burkett ; Martin St. Maurice ; William A. Donaldson ;

Abstract: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3β. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17–29) were prepared and evaluated for the inhibition of GSK-3β at 25 μM. The IC50 values of five of these compounds was determined; the two best inhibitors are 5-[(4′-chloro-2-pyridinyl)methylene]hydantoin (IC50 = 2.14 ± 0.18 μM) and 5-[(6′-bromo-2-pyridinyl)methylene]hydantoin (IC50 = 3.39 ± 0.16 μM). The computational docking of the compounds with GSK-3β (pdb 1q41) revealed poses with hydrogen bonding to the backbone at Val135. The 5-[(heteroaryl)methylene]hydantoins did not strongly inhibit other metalloenzymes, demonstrating poor inhibitory activity against matrix metalloproteinase-12 at 25 μM and against human carbonic anhydrase at 200 μM, and were not inhibitors for Staphylococcus aureus pyruvate carboxylase at concentrations >1000 μM.

Keywords: nitrogen heterocycles ; glycogen synthase kinase 3β ; computational docking

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Product Details of [ 1805434-14-3 ]

CAS No. :1805434-14-3
Formula : C8H6BrF2NO
M.W : 250.04
SMILES Code : O=CC1=NC(C)=CC(Br)=C1C(F)F
MDL No. :MFCD25375604

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