1615253-64-9Relevant articles and documents
2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors
Patel, Leena,Chandrasekhar, Jayaraman,Evarts, Jerry,Haran, Aaron C.,Ip, Carmen,Kaplan, Joshua A.,Kim, Musong,Koditek, David,Lad, Latesh,Lepist, Eve-Irene,McGrath, Mary E.,Novikov, Nikolai,Perreault, Stephane,Puri, Kamal D.,Somoza, John R.,Steiner, Bart H.,Stevens, Kirk L.,Therrien, Joseph,Treiberg, Jennifer,Villase?or, Armando G.,Yeung, Arthur,Phillips, Gary
, p. 3532 - 3548 (2016/05/19)
Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) is an appealing target for several hematological malignancies and inflammatory diseases. Herein, we describe the discovery and optimization of a series of propeller shaped PI3Kδ inhibitors comprising a novel triaminopyrimidine hinge binder. Combinations of electronic and structural strategies were employed to mitigate aldehyde oxidase mediated metabolism. This medicinal chemistry effort culminated in the identification of 52, a potent and highly selective inhibitor of PI3Kδ that demonstrates efficacy in a rat model of arthritis.
