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3D Pharmacophore Model-Assisted Discovery of Novel CDC7 Inhibitors.

ACS medicinal chemistry letters (2011-10-13)
Mika Lindvall, Christopher McBride, Maureen McKenna, Thomas G Gesner, Asha Yabannavar, Kent Wong, Song Lin, Annette Walter, Cynthia M Shafer
ABSTRACT

A ligand-based 3D pharmacophore model for serine/threonine kinase CDC7 inhibition was created and successfully applied in the discovery of novel 2-(heteroaryl)-6,7-dihydrothieno[3,2-c]pyridin-4(5H)-ones. The pharmacophore model provided a hypothesis for lead generation missed by docking to a homology model. Medicinal chemistry exploration of the series revealed clear structure-activity relationships consistent with the pharmacophore model and pointed to further optimization opportunities.

MATERIALS
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Product Description

Sigma-Aldrich
4-Pyrazoleboronic acid pinacol ester, 97%