Compelling P1 substituent affect on metalloprotease binding profile enables the design of a novel cyclohexyl core scaffold with excellent MMP selectivity and HER-2 sheddase inhibition

Autor:	Yun-Long Li, Wenqing Yao, Eric Shi, Jordan S. Fridman, Maryanne Covington, Peggy Scherle, Ding-Quan Qian, Jincong Zhuo, Kamna Katiyar, Colin Zhang, Meizhong Xu, David M. Burns, Cindy A. Marando, Richard Wynn, Steve Friedman, Yanlong Li, Chunhong He, Brian Metcalf
Rok vydání:	2009
Předmět:	Scaffold medicine.drug_class Stereochemistry Receptor ErbB-2 Clinical Biochemistry Substituent Pharmaceutical Science Carboxamide Antineoplastic Agents Hydroxamic Acids Biochemistry Chemical synthesis Substrate Specificity chemistry.chemical_compound ADAM10 Protein Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Humans Molecular Biology Metalloproteinase Hydroxamic acid Chemistry Organic Chemistry Membrane Proteins Sheddase ADAM Proteins Drug Design Molecular Medicine Matrix Metalloproteinase 2 Amyloid Precursor Protein Secretases Selectivity Protein Binding
Zdroj:	Bioorganicmedicinal chemistry letters. 19(13)
ISSN:	1464-3405
Popis:	A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core that exhibited excellent HER-2 potency and unprecedented MMP-selectivity that we believe would not have been possible via conventional P1' perturbations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ed15c6394336e639e5722ae7c33a8f8 https://pubmed.ncbi.nlm.nih.gov/19457660 Zobrazit plný text záznamu Full Text from ScienceDirect