compound 7d [PMID: 29672049]   

GtoPdb Ligand ID: 9937

Compound class: Synthetic organic
Comment: Compound 7d is a FLT3 inhibitor [1]. It was identified as a lead compound in a medicinal chemistry study to find novel chemical scaffolds that offer improved FLT3 inhibition, and that provide compounds with potential clinical oncology therapeutic value for FLT3-driven cancers. Similar levels of inhibition of wild type and D835Y-mutated FLT3 enzymes suggests that compound 7d is a Type I (ATP binding site) kinase inhibitor. In comparison to quizartinib, a single dose of compound 7d produces a longer-lived inhibition of FLT3 and STAT5 phosphorylation in xenograft mice.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 106.15
Molecular weight 490.32
XLogP 3.5
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES NC1CCC(CC1)Nc1nc(Nc2ccc(cc2)CN2CCOCC2)c2c(n1)n(cn2)C1CCCC1
Isomeric SMILES N[C@@H]1CC[C@H](CC1)Nc1nc(Nc2ccc(cc2)CN2CCOCC2)c2c(n1)n(cn2)C1CCCC1
InChI InChI=1S/C27H38N8O/c28-20-7-11-22(12-8-20)31-27-32-25(24-26(33-27)35(18-29-24)23-3-1-2-4-23)30-21-9-5-19(6-10-21)17-34-13-15-36-16-14-34/h5-6,9-10,18,20,22-23H,1-4,7-8,11-17,28H2,(H2,30,31,32,33)/t20-,22-
InChI Key SAEGVASGMTZGFI-AQYVVDRMSA-N
References
1. Gucký T, Řezníčková E, Radošová Muchová T, Jorda R, Klejová Z, Malínková V, Berka K, Bazgier V, Ajani H, Lepšík M et al.. (2018)
Discovery of N2-(4-Amino-cyclohexyl)-9-cyclopentyl- N6-(4-morpholin-4-ylmethyl-phenyl)- 9H-purine-2,6-diamine as a Potent FLT3 Kinase Inhibitor for Acute Myeloid Leukemia with FLT3 Mutations.
J. Med. Chem., 61 (9): 3855-3869. [PMID:29672049]