1428733-96-3Relevant academic research and scientific papers
PF-04859989 as a template for structure-based drug design: Identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency
Dounay, Amy B.,Anderson, Marie,Bechle, Bruce M.,Evrard, Edelweiss,Gan, Xinmin,Kim, Ji-Young,McAllister, Laura A.,Pandit, Jayvardhan,Rong, Suobao,Salafia, Michelle A.,Tuttle, Jamison B.,Zawadzke, Laura E.,Verhoest, Patrick R.
, p. 1961 - 1966 (2013/04/23)
The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein. The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties. Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a kinact/Ki value of 112,000 M-1 s -1 and lipophilic efficiency (LipE) of 8.53. The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency.
