Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent β isoform selective phosphatidylinositol 3-kinase inhibitors

Autor:	Sanchez Robert, Jeanelle McSurdy-Freed, Hongyi Yu, Michael L. Moore, Rosanna Tedesco, Mary Ann Hardwicke, Karl F. Erhard, Ralph A. Rivero, Kaushik Raha, Michael D. Spengler, Juan I. Luengo, Ramona Plant, Hong Lin, Michael D. Schaber, Cynthia M. Rominger
Rok vydání:	2012
Předmět:	Gene isoform education Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Substrate Specificity chemistry.chemical_compound Structure-Activity Relationship Cell Line Tumor Drug Discovery PTEN Structure–activity relationship Humans Protein Isoforms Phosphatidylinositol Molecular Biology Protein kinase B Protein Kinase Inhibitors Cell Proliferation Phosphoinositide-3 Kinase Inhibitors biology Kinase Organic Chemistry PTEN Phosphohydrolase humanities Pyrimidines chemistry biology.protein Molecular Medicine Phosphorylation Growth inhibition
Zdroj:	Bioorganicmedicinal chemistry letters. 22(9)
ISSN:	1464-3405
Popis:	A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (∼ 0.100 μM IC(50)) growth inhibition in a PTEN deficient cancer cell line.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39aeedab2fa3b426ab69e2e507b41350 https://pubmed.ncbi.nlm.nih.gov/22475557 Zobrazit plný text záznamu Full Text from ScienceDirect