Download MendeleyIdentification and structure activity relationships of quinoline tertiary alcohol modulators of ROR gamma t.
Kummer, D.A., Cummings, M.D., Abad, M., Barbay, J., Castro, G., Wolin, R., Kreutter, K.D., Maharoof, U., Milligan, C., Nishimura, R., Pierce, J., Schalk-Hihi, C., Spurlino, J., Urbanski, M., Venkatesan, H., Wang, A., Woods, C., Xue, X., Edwards, J.P., Fourie, A.M., Leonard, K.(2017) Bioorg Med Chem Lett 27: 2047-2057
- PubMed: 28318945
- DOI: https://doi.org/10.1016/j.bmcl.2017.02.044
- Primary Citation of Related Structures:
5UFO, 5UFR, 5UHI - PubMed 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.
Organizational Affiliation:
Discovery Immunology, Janssen Research and Development, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: dkummer1@its.jnj.com.
