2017
DOI: 10.1016/j.bmcl.2017.01.016
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Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3Kδ inhibitors

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Cited by 15 publications
(12 citation statements)
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“…From the same team of researchers, another PI3Kδ inhibitor, 42 , with higher activity and selectivity over β isoform than 41 was reported (Fig. 17 ) [ 131 ]. The cellular activity (B-cells) of 42 (IC 50 = 5.8 nM) was slightly better than 41 .…”
Section: Serine/threonine Kinase Inhibitorsmentioning
confidence: 99%
“…From the same team of researchers, another PI3Kδ inhibitor, 42 , with higher activity and selectivity over β isoform than 41 was reported (Fig. 17 ) [ 131 ]. The cellular activity (B-cells) of 42 (IC 50 = 5.8 nM) was slightly better than 41 .…”
Section: Serine/threonine Kinase Inhibitorsmentioning
confidence: 99%
“…A total of 46 PI3Kδ structures have been deposited into the PDB (as of 25 January 2019). In addition to the murine ΔABD-p110δ structure, human p110δ/iSH2 structures have also been published (PDB ID 5T8F, 5UBT, 5VLR), with lower resolution than the ΔABD structures (2.8–2.9 Å) [93,94,95].…”
Section: Structural Biology Of Pi3kmentioning
confidence: 99%
“…To give further insight into how these families of inhibitors achieve their selectivity, crystal structures of the same inhibitor have been determined in two isoforms [94,108,116]. The crystal structure of the quinazoline-based inhibitor 39 in p110δ (PDB ID 5IS5) reveals that the acetyl-piperazine group of the ligand stacks with δTrp760 using the tryptophan shelf (Figure 7a) [116].…”
Section: Structural Determinants Of Isoform Selectivitymentioning
confidence: 99%
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“…Pyrrolotriazine 2 was recently reported as a very potent PI3Kδ inhibitor (Figure 2). 12 Despite excellent potency in a CD69 human whole blood (hWB) assay, this molecule lacked selectivity over PI3Kα and PI3Kγ. Furthermore, its high polar surface area (PSA = 124 Å 2 ) resulted in poor in vitro ADME properties.…”
Section: ■ Chemistrymentioning
confidence: 99%