Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

Autor:	S. David Kimball, Kenneth G. Carson, Jason P. Healy, Michael J. Hunter, Jerry A. Taylor, Min Shen, Terry R. Stouch, Xuan Chuan Yu, Qinghong Fu, Alan Wilson, Qingyun Liu, Alexander Heim-Riether, Amr Nouraldeen, Ronald V. Swanson, Jonathan C. Swaffield, Marianne Carlsen, Amy Xu, Philip E. Keyes, Isaac Hoffman, Kanchan G. Jhaver, Rick Avery Finch, Ann Marie DiGeorge Foushee, Leslie W. Tari, Theodore C. Jessop, Steve Anderson, Tamas Oravecz, Maricar Miranda, James E. Tarver, David J. Augeri
Rok vydání:	2009
Předmět:	Models Molecular medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Chemical synthesis Deoxycytidine Structure-Activity Relationship Pharmacokinetics In vivo Drug Discovery Deoxycytidine Kinase medicine Potency Molecular Biology Protein Kinase Inhibitors chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure Organic Chemistry Stereoisomerism Deoxycytidine kinase In vitro Enzyme chemistry Drug Design Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 19(23)
ISSN:	1464-3405
Popis:	A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff32e10f0d7834c04415350e63a43b22 https://pubmed.ncbi.nlm.nih.gov/19836232 Zobrazit plný text záznamu Full Text from ScienceDirect