Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery was written by Erlanson, Daniel A.;Arndt, Joseph W.;Cancilla, Mark T.;Cao, Kathy;Elling, Robert A.;English, Nicki;Friedman, Jessica;Hansen, Stig K.;Hession, Cathy;Joseph, Ingrid;Kumaravel, Gnanasambandam;Lee, Wen-Cherng;Lind, Ken E.;McDowell, Robert S.;Miatkowski, Konrad;Nguyen, Christine;Nguyen, Thinh B.;Park, Sophia;Pathan, Nuzhat;Penny, David M.;Romanowski, Michael J.;Scott, Daniel;Silvian, Laura;Simmons, Robert L.;Tangonan, Bradley T.;Yang, Wenjin;Sun, Lihong. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Application In Synthesis of 1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid This article mentions the following:
We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chem., this led to the discovery of the potent and highly selective inhibitor of PDK1 33 (I), which binds in the ‘DFG-out’ conformation. In the experiment, the researchers used many compounds, for example, 1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (cas: 1001413-01-9Application In Synthesis of 1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid).
1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (cas: 1001413-01-9) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the 锜?bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the 锜?bonds. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Application In Synthesis of 1-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid