Discovery of carbazole carboxamides as novel RORγt inverse agonists

European Journal of Medicinal Chemistry
Yafei HuangYonghui Wang

Abstract

A novel series of carbazole carboxamides was discovered as potent RORγt inverse agonists using a scaffold hybridization strategy. Structure-activity relationship exploration on the amide linker, carbazole ring and arylsulfone moiety of the hybrid amide 3a led to identification of potent RORγt inverse agonists. Compound 6c was found to have a good RORγt activity with an IC50of 58.5 nM in FRET assay, and reasonable inhibitory activity in mouse Th17 cell differentiation assay (58.8% inhibition at 0.3 μM). The binding mode of carbazole carboxamides in RORγt ligand binding domain was discussed.

References

Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yutaka KomiyamaYoichiro Iwakura
May 27, 2008·Journal of Autoimmunity·Valérie DardalhonAna C Anderson
Jan 31, 2012·Chemistry & Biology·Thomas P BurrisPatrick R Griffin
Jul 14, 2012·Trends in Endocrinology and Metabolism : TEM·Laura A Solt, Thomas P Burris
Sep 6, 2012·European Journal of Immunology·Jun R Huh, Dan R Littman
Feb 8, 2014·Journal of Medicinal Chemistry·Benjamin P Fauber, Steven Magnuson
Apr 22, 2014·Immunity·Jacob S Lee, Daniel J Cua
May 6, 2014·Drug Discovery Today·Fujio IsonoShuichiro Ito
Jun 6, 2014·ACS Medicinal Chemistry Letters·Ting YangYonghui Wang
Jul 16, 2014·Cell Research·Chen Dong
Aug 19, 2014·Trends in Pharmacological Sciences·Jianfei YangTetsuya Yamagata
Dec 17, 2014·Acta Pharmacologica Sinica·Yan ZhangYong Xu
Jul 21, 2015·ACS Medicinal Chemistry Letters·Yonghui WangXichen Lin
Aug 19, 2015·Bioorganic & Medicinal Chemistry·Yonghui WangXichen Lin
Aug 21, 2016·Bioorganic & Medicinal Chemistry Letters·Patrick CyrJames J Crawford
Sep 16, 2016·Expert Opinion on Therapeutic Patents·Sarah M BronnerJames J Crawford
Feb 20, 2018·ACS Medicinal Chemistry Letters·Yonghui WangFeng Ren

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Citations

Jun 24, 2018·Chemistry & Biodiversity·Moustafa T Gabr, Mohammed S Abdel-Raziq
Oct 30, 2019·ChemMedChem·Ayumu SatoSatoshi Yamamoto
Apr 1, 2020·Frontiers in Immunology·Alessia Capone, Elisabetta Volpe
Jul 19, 2019·Scientific Reports·Xiaofei ShiCong-Qiu Chu
Aug 7, 2019·Annual Review of Pharmacology and Toxicology·Anton M Jetten, Donald N Cook
Dec 5, 2020·European Journal of Medicinal Chemistry·Yuehan XiaYonghui Wang
Jun 13, 2021·Autoimmunity Reviews·Kun XiangDe-Guang Wang

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