3416-18-0Relevant articles and documents
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Gassman,Campbell
, p. 1437 (1971)
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Design, synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure
Cheng, Kai,Li, Shiyu,Lv, Xiao,Tian, Yongbin,Kong, Haiyan,Huang, Xufeng,Duan, Yajun,Han, Jihong,Xie, Zhouling,Liao, Chenzhong
supporting information, p. 1012 - 1018 (2019/02/24)
Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50 = 3 nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.
LRRK2 INHIBITORS
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, (2013/02/28)
Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.
Synthesis, in silico, in vitro, and in vivo investigation of 5-[ 11C]methoxy-substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2
Caballero, Julio,Mu?oz, Camila,Alzate-Morales, Jans H.,Cunha, Susana,Gano, Lurdes,Bergmann, Ralf,Steinbach, Joerg,Kniess, Torsten
, p. 272 - 280 (2013/02/23)
Sunitinib (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels in tumor tissue giving valuable information for anti-angiogenic therapy. Herein we report the synthesis of 5-methoxy-sunitinib 5 and its 11C-radiolabeled analog [11C]-5. The non-radioactive reference compound 5 was prepared by Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. A binding constant (Kd) of 20 nM for 5 was determined by competition binding assay against VEGFR-2. In addition, the binding mode of sunitinib and its 5-methoxy substituted derivative was studied by flexible docking simulations. These studies revealed that the substitution of the fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect the inhibitor orientation, but affected the electrostatic and van der Waals interactions of the ligand with residues near the DFG motif of VEGFR-2. 5-[11C]methoxy-sunitinib ([11C]-5) was synthesized by reaction of the desmethyl precursor with [11C]CH3I in the presence of DMF and NaOH in 17 ± 3% decay-corrected radiochemical yield at a specific activity of 162-205 GBq/μmol (EOS). In vivo stability studies of [11C]-5 in rat blood showed that more than 70% of the injected compound was in blood stream, 60 min after administration.
