Pyrazolobenzodiazepines: part I. Synthesis and SAR of a potent class of kinase inhibitors

Autor:	Hong Yang, Irena Daniewski, Dorota Miklowski, Brian Higgins, Giacomo Pizzolato, Fred Konzelmann, Christine Lukacs, Peter Michael Wovkulich, Rossman Pamela Loreen, Kenneth Kolinsky, Xuefeng Yin, Wei Chung-Chen, Grace Ju, Qingjie Ding, Kshitij Chhabilbhai Thakkar, Amy Swain, Jin-Jun Liu
Rok vydání:	2010
Předmět:	Models Molecular Clinical Biochemistry Pharmaceutical Science Mice Nude Antineoplastic Agents Biochemistry Benzodiazepines Inhibitory Concentration 50 Mice Structure-Activity Relationship Cyclin-dependent kinase Cell Line Tumor Neoplasms Drug Discovery Structure–activity relationship Animals Humans Cytotoxicity Molecular Biology Protein Kinase Inhibitors biology Neovascularization Pathologic Kinase Chemistry Organic Chemistry Cyclin-dependent kinase 2 Cell Cycle Cyclin-Dependent Kinase 2 Cell culture Enzyme inhibitor Cancer cell Cancer research biology.protein Molecular Medicine Pyrazoles Protein Binding
Zdroj:	Bioorganicmedicinal chemistry letters. 20(20)
ISSN:	1464-3405
Popis:	A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure-activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines. Further exploration has revealed that this class of compounds inhibits several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. Together, these properties suggest a compelling basis for their use as antitumor agents.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3779ce22a7db6be82920da5853d825bf https://pubmed.ncbi.nlm.nih.gov/20832307 Zobrazit plný text záznamu Full Text from ScienceDirect