Back to Search
Start Over
Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2017 Dec 01; Vol. 141, pp. 373-385. Date of Electronic Publication: 2017 Oct 06. - Publication Year :
- 2017
-
Abstract
- VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Angiogenesis Inhibitors chemical synthesis
Angiogenesis Inhibitors chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Human Umbilical Vein Endothelial Cells drug effects
Humans
Indazoles chemistry
Molecular Docking Simulation
Molecular Structure
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Receptor Protein-Tyrosine Kinases metabolism
Structure-Activity Relationship
Thiourea chemical synthesis
Thiourea chemistry
Angiogenesis Inhibitors pharmacology
Antineoplastic Agents pharmacology
Drug Discovery
Indazoles pharmacology
Neovascularization, Pathologic drug therapy
Protein Kinase Inhibitors pharmacology
Receptor Protein-Tyrosine Kinases antagonists & inhibitors
Thiourea pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 141
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29032031
- Full Text :
- https://doi.org/10.1016/j.ejmech.2017.10.008