Back to Search
Start Over
Synthesis and biological evaluation of solubilized sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2019 Apr 15; Vol. 27 (8), pp. 1529-1545. Date of Electronic Publication: 2019 Feb 25. - Publication Year :
- 2019
-
Abstract
- Replacing one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 with a variety of sulfonamide-linked solubilizing substituents produced a new class of active and potent PI3Kα inhibitors, with several derivatives demonstrating high PI3Kα enzyme potency and good cellular potency in two human derived cell lines. The overall results suggest a preference for linear and somewhat flexible solubilizing functions. From this series, compound 16, also known as SN32976, was selected for advanced preclinical evaluation.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Cell Line, Tumor
Cell Proliferation drug effects
Drug Evaluation, Preclinical
Female
Humans
Inhibitory Concentration 50
Mice
Neoplasms drug therapy
Phosphatidylinositol 3-Kinases metabolism
Phosphoinositide-3 Kinase Inhibitors pharmacology
Phosphoinositide-3 Kinase Inhibitors therapeutic use
Protein Subunits antagonists & inhibitors
Protein Subunits metabolism
Structure-Activity Relationship
Sulfonamides pharmacology
Sulfonamides therapeutic use
Transplantation, Heterologous
Phosphatidylinositol 3-Kinases chemistry
Phosphoinositide-3 Kinase Inhibitors chemical synthesis
Sulfonamides chemistry
Triazines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 27
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30850264
- Full Text :
- https://doi.org/10.1016/j.bmc.2019.02.050