1615252-58-8Relevant 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.
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 0759, (2014/07/08)
The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts thereof, in which n, m, R1, R2, and R3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.
