Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors

Autor:	Michael J. Romanowski, Yafan Lu, Junfa Fan, Raymond V. Fucini, Hans E. Purkey, Willard Lew, Erica VanderPorten, Joshua C. Yoburn, Bruce T. Fahr, Minna Bui, Ingrid C. Choong, Hanan Emily, Jiang Zhu, Phuongly Pham, Yang Liu, Marc J. Evanchik, Robert A. Elling, Kenneth J. Barr, Wenjin Yang
Rok vydání:	2008
Předmět:	Stereochemistry medicine.drug_class Pyridines Chemistry Pharmaceutical Clinical Biochemistry Amino Acid Motifs Molecular Conformation Pharmaceutical Science Carboxamide Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Crystallography X-Ray Biochemistry PLK1 Chemical synthesis Inhibitory Concentration 50 Structure-Activity Relationship Adenosine Triphosphate Proto-Oncogene Proteins Drug Discovery Pyrazolopyridine medicine Structure–activity relationship Humans Molecular Biology biology Kinase Chemistry Organic Chemistry Cell Cycle Phenotype Models Chemical Enzyme inhibitor Drug Design biology.protein Molecular Medicine Pyrazoles
Zdroj:	Bioorganicmedicinal chemistry letters. 18(20)
ISSN:	1464-3405
Popis:	A series of 2-amino-pyrazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors based on a low micromolar hit. The SAR was developed to provide compounds exhibiting low nanomolar inhibitory activity of Plk1; the phenotype of treated cells is consistent with Plk1 inhibition. A co-crystal structure of one of these compounds with zPlk1 confirms an ATP-competitive binding mode.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b95acafa1a6d4c413fbf0fb6fce7aae https://pubmed.ncbi.nlm.nih.gov/18793847 Zobrazit plný text záznamu Full Text from ScienceDirect