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Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2015 Nov 02; Vol. 104, pp. 139-47. Date of Electronic Publication: 2015 Oct 08. - Publication Year :
- 2015
-
Abstract
- A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, 11a and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, 11a exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 values of 0.014 μM and 0.45 μM, respectively. Furthermore, compound 11a also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T315I) inhibitors.<br /> (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Antineoplastic Agents administration & dosage
Antineoplastic Agents chemistry
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fusion Proteins, bcr-abl metabolism
Humans
Indazoles chemistry
K562 Cells
Molecular Docking Simulation
Molecular Structure
Piperazines chemistry
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Fusion Proteins, bcr-abl antagonists & inhibitors
Indazoles pharmacology
Piperazines pharmacology
Protein Kinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 104
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26451772
- Full Text :
- https://doi.org/10.1016/j.ejmech.2015.09.034