3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent

Autor:	Xichen Lin, Michael E. Muratore, Huijie Li, Ami S. Lakdawala, Jakob Busch-Petersen, Ruth R. Osborn, David D. Miller, Jeffrey K. Kerns, Rick P. C. Cousins, Ian Robert Baldwin, Paul Bamborough, John Yonchuk, Ann M. Bullion, Lin Guoliang, Jeffrey C. Boehm, Wei Fu, John A. Christopher, Edward F. Webb, Roderick S. Davis, William L. Rumsey, Rita Field, Jeremy John Payne, Hong Nie
Rok vydání:	2018
Předmět:	0301 basic medicine Indole test Ligand efficiency Chemistry Stereochemistry Organic Chemistry Regulator Substituent NF-κB IκB kinase Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology In vivo Drug Discovery Potency
Zdroj:	ACS Medicinal Chemistry Letters. 9:1164-1169
ISSN:	1948-5875
Popis:	[Image: see text] IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::782cb7b7a63c400db0be5e5461917822 https://doi.org/10.1021/acsmedchemlett.8b00291 Zobrazit plný text záznamu