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Identification and structure activity relationships of quinoline tertiary alcohol modulators of RORγt.

Authors :
Kummer DA
Cummings MD
Abad M
Barbay J
Castro G
Wolin R
Kreutter KD
Maharoof U
Milligan C
Nishimura R
Pierce J
Schalk-Hihi C
Spurlino J
Urbanski M
Venkatesan H
Wang A
Woods C
Xue X
Edwards JP
Fourie AM
Leonard K
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 May 01; Vol. 27 (9), pp. 2047-2057. Date of Electronic Publication: 2017 Feb 21.
Publication Year :
2017

Abstract

A high-throughput screen of the ligand binding domain of the nuclear receptor retinoic acid-related orphan receptor gamma t (RORγt) employing a thermal shift assay yielded a quinoline tertiary alcohol hit. Optimization of the 2-, 3- and 4-positions of the quinoline core using structure-activity relationships and structure-based drug design methods led to the discovery of a series of modulators with improved RORγt inhibitory potency and inverse agonism properties.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
27
Issue :
9
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
28318945
Full Text :
https://doi.org/10.1016/j.bmcl.2017.02.044