Results: 5

1.
Figure 1

Figure 1. From: An Amino-indazole Scaffold with Spectrum Selective Kinase Inhibition of FLT3, PDGFR? and Kit.

Scaffold design strategy.

Xianming Deng, et al. Bioorg Med Chem Lett. ;22(14):4579-4584.
2.
Figure 2

Figure 2. From: An Amino-indazole Scaffold with Spectrum Selective Kinase Inhibition of FLT3, PDGFR? and Kit.

KINOMEscan profiling of 4. The compound was screened at a concentration 10 µM against 402 kinases and the most potently bound kinases (score ≤ 0.1) are indicated by red circles. The kinase dendrogram was adapted and reproduced with permission from Cell signaling Technology, Inc.

Xianming Deng, et al. Bioorg Med Chem Lett. ;22(14):4579-4584.
3.
Figure 3

Figure 3. From: An Amino-indazole Scaffold with Spectrum Selective Kinase Inhibition of FLT3, PDGFR? and Kit.

Modeling study of 4. a) Binding mode comparison of 4 with HG-7-85-01 in the co-crystal structure of c-Src (PDB ID: 4agw). b) Binding mode comparison of 4 with AP24534 in the co-crystal structure of Bcr-Abl-T315I (PDB ID: 3ik3). 4 (green carbon atom), HG-7-85-01 (cyan carbon atom), AP24534 (yellow carbon atom, the structure was included in supplementary file) and hydrogen bonds indicated by hatched lines.

Xianming Deng, et al. Bioorg Med Chem Lett. ;22(14):4579-4584.
4.
Scheme 1

Scheme 1. From: An Amino-indazole Scaffold with Spectrum Selective Kinase Inhibition of FLT3, PDGFR? and Kit.

Synthetic route of 4. Reagents and conditions: (a) NH2NH2, n-BuOH, 130 °C, overnight, 98%; (b) cyclopropanecarbonyl chloride, pyridine, 0 °C, 77%; (c) (3-(ethoxycarbonyl)phenyl)boronic acid, Pd(dppf)CI2, Na2CO3 (1 N, aq.). dioxane, 100 °C, 80%; (d) LiOH, THF/MeOH/H2O; (e) 4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline, HATU, DIEA, DMSO, 45%.

Xianming Deng, et al. Bioorg Med Chem Lett. ;22(14):4579-4584.
5.
Scheme 2

Scheme 2. From: An Amino-indazole Scaffold with Spectrum Selective Kinase Inhibition of FLT3, PDGFR? and Kit.

Synthetic route of 22. Reagents and conditions: (a) phenyl chloroformate, pyridine, 0 °C, 40%; (b) LiAIH4, dioxane, reflux, 53%; (c) pinaool diboron ester, Pd(dppf)CI2, dppf, KOAc, DMF, 100 °C, 90%; (d) N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-iodobenzamide, Pd(dppf)CI2. Na2CO3 (1 N, aq.), dioxane, 100 °C. 15%.

Xianming Deng, et al. Bioorg Med Chem Lett. ;22(14):4579-4584.

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