Efforts towards the optimization of a bi-aryl class of potent IRAK4 inhibitors

Autor:	Christopher Sondey, Theirry Fischmann, Kristine Devito, Haiquin Tang, W. Michael Seganish, Rui Zhang, Jennifer Hanisak, Hon-Chung Tsui, Deen Tulshian, Daniel Lundell, Charles G. Garlisi, William T. McElroy, Xiaoda Niu, James Fossetta, James R. Tata
Rok vydání:	2016
Předmět:	0301 basic medicine Clinical Biochemistry Pharmaceutical Science Computational biology Plasma protein binding Molecular Dynamics Simulation Pyrazole Crystallography X-Ray Ligands Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Drug Discovery Animals Humans Structure–activity relationship Protein Kinase Inhibitors Molecular Biology Binding Sites Ligand efficiency Aryl Organic Chemistry IRAK4 Protein Structure Tertiary Rats Interleukin-1 Receptor-Associated Kinases 030104 developmental biology chemistry Chemical diversity Pyrazoles Molecular Medicine Half-Life Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 26:4250-4255
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2016.07.048
Popis:	IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series. These compounds maintain potent IRAK4 activity and desirable ligand efficiency. Rat clearance and a variety of off target activities were also examined, resulting in encouraging data with tractable SAR.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f36bde751943a6860892af80d72d0b9 https://doi.org/10.1016/j.bmcl.2016.07.048 Zobrazit plný text záznamu Full Text from ScienceDirect