Loading…
SAR Exploration Guided by LE and Fsp3: Discovery of a Selective and Orally Efficacious RORγ Inhibitor
A novel series of RORγ inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp3 carbon atoms (Fsp3), significant improvement of metabolic stability as well as reduction...
Saved in:
Published in: | ACS medicinal chemistry letters 2016-01, Vol.7 (1), p.23-27 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | A novel series of RORγ inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp3 carbon atoms (Fsp3), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORγ inhibitor 3z. |
---|---|
ISSN: | 1948-5875 1948-5875 |
DOI: | 10.1021/acsmedchemlett.5b00253 |