Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors

Autor:	Michael D. Spengler, Rosanna Tedesco, Sanchez Robert, Michael D. Schaber, Ramona Plant, Hong Lin, Mary Ann Hardwicke, Karl F. Erhard, James F. Mack, Kaushik Raha, Ralph A. Rivero, Cynthia M. Rominger, Juan I. Luengo, Mark J. Schulz, Jeanelle McSurdy-Freed, Ren Xie, Jin J. Zeng
Rok vydání:	2011
Předmět:	Gene isoform Models Molecular Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Breast Neoplasms Pyrimidinones Biochemistry chemistry.chemical_compound Structure-Activity Relationship Cell Line Tumor Drug Discovery Structure–activity relationship Humans Homology modeling Phosphatidylinositol Molecular Biology Protein Kinase Inhibitors Phosphoinositide-3 Kinase Inhibitors Binding Sites Kinase Organic Chemistry Imidazoles PTEN Phosphohydrolase Isoenzymes Kinetics chemistry Docking (molecular) Molecular Medicine Female Growth inhibition Enantiomer Drug Screening Assays Antitumor Phosphatidylinositol 3-Kinase Gene Deletion Protein Binding
Zdroj:	Bioorganicmedicinal chemistry letters. 22(6)
ISSN:	1464-3405
Popis:	A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a88dac9bc6de289344a6d52a979b9376 https://pubmed.ncbi.nlm.nih.gov/22361133 Zobrazit plný text záznamu Full Text from ScienceDirect