1234479-74-3Relevant articles and documents
Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a potent and selective inhibitor of big MAP kinase 1
Deng, Xianming,Yang, Qingkai,Kwiatkowski, Nicholas,Sim, Taebo,McDermott, Ultan,Settleman, Jeffrey E.,Lee, Jiing-Dwan,Gray, Nathanael S.
, p. 195 - 200 (2011)
Kinome-wide selectivity profiling of a collection of 2-amino-pyrido[2,3-d] pyrimidines followed by cellular structure-activity relationship-guided optimization resulted in the identification of moderately potent and selective inhibitors of BMK1/ERK5 exemp
Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6 H-benzo[ e]pyrimido[5,4- b][1,4]diazepin-6-one Scaffold
Ferguson, Fleur M.,Liu, Yan,Harshbarger, Wayne,Huang, Ling,Wang, Jinhua,Deng, Xianming,Capuzzi, Stephen J.,Muratov, Eugene N.,Tropsha, Alexander,Muthuswamy, Senthil,Westover, Kenneth D.,Gray, Nathanael S.
, p. 7817 - 7826 (2020/08/21)
Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that is overexpressed in gastrointestinal cancers, including esophageal, gastric, colorectal, and pancreatic cancers. DCLK1 is also used as a marker of tuft cells, which regulate type II immunity in the gut. However, the substrates and functions of DCLK1 are understudied. We recently described the first selective DCLK1/2 inhibitor, DCLK1-IN-1, developed to aid the functional characterization of this important kinase. Here we describe the synthesis and structure-activity relationships of 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one DCLK1 inhibitors, resulting in the identification of DCLK1-IN-1.
Discovery of a Series of 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-ones as Selective PI3K-δ/γ Inhibitors
Ferguson, Fleur M.,Ni, Jing,Zhang, Tinghu,Tesar, Bethany,Sim, Taebo,Kim, Nam Doo,Deng, Xianming,Brown, Jennifer R.,Zhao, Jean J.,Gray, Nathanael S.
supporting information, p. 908 - 912 (2016/10/22)
Dual inhibition of PI3K-δ and PI3K-γ is an established therapeutic strategy for treatment of hematological malignancies. Reported molecules targeting PI3K-δ/γ selectively are chemically similar and based upon isoquinolin-1(2H)-one or quinazolin-4(3H)-one scaffolds. Here we report a chemically distinct series of potent, selective PI3K-δ/γ inhibitors based on a 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one scaffold with comparable biochemical potency and cellular effects on PI3K signaling. We envisage these molecules will provide useful leads for development of next-generation PI3K-δ/γ targeting therapeutics.
