Synthesis and evaluation of novel 3,4,6-substituted 2-quinolones as FMS kinase inhibitors.
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Wall MJ, Chen J, Meegalla S, Ballentine SK, Wilson KJ, DesJarlais RL, Schubert C, Chaikin MA, Crysler C, Petrounia IP, Donatelli RR, Yurkow EJ, Boczon L, Mazzulla M, Player MR, Patch RJ, Manthey CL, Molloy C, Tomczuk B, Illig CR
Synthesis and evaluation of novel 3,4,6-substituted 2-quinolones as FMS kinase inhibitors.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2097-102. doi: 10.1016/j.bmcl.2008.01.088. Epub 2008 Jan 30.
- PubMed ID
- 18289848 [ View in PubMed]
- Abstract
A series of 3,4,6-substituted 2-quinolones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). The fully optimized compound, 4-(4-ethyl-phenyl)-3-(2-methyl-3H-imidazol-4-yl)-2-quinolone-6-carbonitrile 21b, has an IC(50) of 2.5 nM in an in vitro assay and 5.0 nM in a bone marrow-derived macrophage cellular assay. Inhibition of FMS signaling in vivo was also demonstrated in a mouse pharmacodynamic model.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 6-CHLORO-3-(3-METHYLISOXAZOL-5-YL)-4-PHENYLQUINOLIN-2(1H)-ONE Macrophage colony-stimulating factor 1 receptor IC 50 (nM) 140 N/A N/A Details