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Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Oct 01; Vol. 18 (19), pp. 7113-20. Date of Electronic Publication: 2010 Jul 25. - Publication Year :
- 2010
-
Abstract
- A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Aurora Kinases
Cell Cycle drug effects
Cell Proliferation drug effects
Computational Biology
Crystallography, X-Ray
Drug Screening Assays, Antitumor
Enzyme Inhibitors chemistry
HL-60 Cells
Humans
Male
Mice
Mice, SCID
Models, Molecular
Molecular Dynamics Simulation
Molecular Structure
Neoplasms, Experimental drug therapy
Pyrazoles chemical synthesis
Pyrazoles chemistry
Stereoisomerism
Structure-Activity Relationship
Thiophenes chemical synthesis
Thiophenes chemistry
Transplantation, Heterologous
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
Protein Serine-Threonine Kinases antagonists & inhibitors
Pyrazoles pharmacology
Thiophenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 18
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20817473
- Full Text :
- https://doi.org/10.1016/j.bmc.2010.07.048