2173134-00-2Relevant academic research and scientific papers
Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1
Casimiro-Garcia, Agustin,Allais, Christophe,Brennan, Agnes,Choi, Chulho,Dower, Gabriela,Farley, Kathleen A.,Fleming, Margaret,Flick, Andrew,Frisbie, Richard K.,Hall, Justin,Hepworth, David,Jones, Hannah,Knafels, John D.,Kortum, Steve,Lovering, Frank E.,Mathias, John P.,Mohan, Sashi,Morgan, Paul M.,Parng, Chuenlei,Parris, Kevin,Pullen, Nick,Schlerman, Franklin,Stansfield, John,Strohbach, Joseph W.,Vajdos, Felix F.,Vincent, Fabien,Wang, Hong,Wang, Xiaolun,Webster, Robert,Wright, Stephen W.
, p. 757 - 784 (2022/01/20)
A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclinical development.
NOVEL PYRIMIDINE CARBOXAMIDES AS INHIBITORS OF VANIN-1 ENZYME
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, (2018/03/26)
Compounds, pharmaceutically acceptable salts thereof, are disclosed wherein the compounds have the structure of (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates a
