Literature DB >> 24388993

Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors.

Yonghui Wang1, Wei Cai2, Guifeng Zhang2, Ting Yang2, Qian Liu2, Yaobang Cheng2, Ling Zhou2, Yingli Ma2, Ziqiang Cheng2, Sijie Lu2, Yong-Gang Zhao2, Wei Zhang2, Zhijun Xiang2, Shuai Wang2, Liuqing Yang2, Qianqian Wu2, Lisa A Orband-Miller3, Yan Xu2, Jing Zhang2, Ruina Gao2, Melanie Huxdorf2, Jia-Ning Xiang2, Zhong Zhong2, John D Elliott2, Stewart Leung2, Xichen Lin2.   

Abstract

Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Multiple sclerosis; RORγt inhibitor; Rheumatoid arthritis; Th17 cell differentiation

Mesh：

Substances：

Year:  2013        PMID： 24388993     DOI： 10.1016/j.bmc.2013.12.021

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN： 0968-0896            Impact factor:   3.641


  14 in total

1.  SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious RORγ Inhibitor.

Authors:  Kazuyuki Hirata; Masayuki Kotoku; Noriyoshi Seki; Takaki Maeba; Katsuya Maeda; Shintaro Hirashima; Takayuki Sakai; Shingo Obika; Akimi Hori; Yasunori Hase; Takayuki Yamaguchi; Yoshiaki Katsuda; Takahiro Hata; Naoki Miyagawa; Kojo Arita; Yukihiro Nomura; Kota Asahina; Yusuke Aratsu; Masafumi Kamada; Tsuyoshi Adachi; Masato Noguchi; Satoki Doi; Paul Crowe; Erin Bradley; Ruo Steensma; Haiyan Tao; Morgan Fenn; Robert Babine; Xiaolin Li; Scott Thacher; Hiromasa Hashimoto; Makoto Shiozaki
Journal:  ACS Med Chem Lett       Date:  2015-11-04       Impact factor: 4.345

2.  Retinoic-acid-orphan-receptor-C inhibition suppresses Th17 cells and induces thymic aberrations.

Authors:  Christine Guntermann; Alessandro Piaia; Marie-Laure Hamel; Diethilde Theil; Tina Rubic-Schneider; Alberto Del Rio-Espinola; Linda Dong; Andreas Billich; Klemens Kaupmann; Janet Dawson; Klemens Hoegenauer; David Orain; Samuel Hintermann; Rowan Stringer; Dhavalkumar D Patel; Arno Doelemeyer; Mark Deurinck; Jens Schümann
Journal:  JCI Insight       Date:  2017-03-09

3.  Identification of an aminothiazole series of RORβ modulators.

Authors:  Rémi Patouret; Christelle Doebelin; Ruben D Garcia-Ordonez; Mi Ra Chang; Claudia Ruiz; Michael D Cameron; Patrick R Griffin; Theodore M Kamenecka
Journal:  Bioorg Med Chem Lett       Date:  2018-03-03       Impact factor: 2.823

Review 4.  ROR nuclear receptors: structures, related diseases, and drug discovery.

Authors:  Yan Zhang; Xiao-yu Luo; Dong-hai Wu; Yong Xu
Journal:  Acta Pharmacol Sin       Date:  2014-12-15       Impact factor: 6.150

5.  Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors.

Authors:  Yonghui Wang; Wei Cai; Yaobang Cheng; Ting Yang; Qian Liu; Guifeng Zhang; Qinghua Meng; Fangbin Han; Yafei Huang; Ling Zhou; Zhijun Xiang; Yong-Gang Zhao; Yan Xu; Ziqiang Cheng; Sijie Lu; Qianqian Wu; Jia-Ning Xiang; John D Elliott; Stewart Leung; Feng Ren; Xichen Lin
Journal:  ACS Med Chem Lett       Date:  2015-05-26       Impact factor: 4.345

6.  Identification of potent RORβ modulators: Scaffold variation.

Authors:  Christelle Doebelin; Rémi Patouret; Ruben D Garcia-Ordonez; Mi Ra Chang; Venkatasubramanian Dharmarajan; Scott Novick; Anthony Ciesla; Sean Campbell; Laura A Solt; Patrick R Griffin; Theodore M Kamenecka
Journal:  Bioorg Med Chem Lett       Date:  2018-08-16       Impact factor: 2.823

7.  From RORγt Agonist to Two Types of RORγt Inverse Agonists.

Authors:  Yonghui Wang; Wei Cai; Ting Tang; Qian Liu; Ting Yang; Liuqing Yang; Yingli Ma; Guifeng Zhang; Yafei Huang; Xiaoxia Song; Lisa A Orband-Miller; Qianqian Wu; Ling Zhou; Zhijun Xiang; Jia-Ning Xiang; Stewart Leung; Liming Shao; Xichen Lin; Mercedes Lobera; Feng Ren
Journal:  ACS Med Chem Lett       Date:  2018-01-22       Impact factor: 4.345

8.  Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists.

Authors:  Xi-Shan Wu; Rui Wang; Yan-Li Xing; Xiao-Qian Xue; Yan Zhang; Yong-Zhi Lu; Yu Song; Xiao-Yu Luo; Chun Wu; Yu-Lai Zhou; Jian-Qin Jiang; Yong Xu
Journal:  Acta Pharmacol Sin       Date:  2016-07-04       Impact factor: 6.150

9.  Retinoic acid-related Orphan Receptor γ (RORγ): connecting sterol metabolism to regulation of the immune system and autoimmune disease.

Authors:  Anton M Jetten; Yukimasa Takeda; Andrzej Slominski; Hong Soon Kang
Journal:  Curr Opin Toxicol       Date:  2018-02-01

10.  Development of a Topical Treatment for Psoriasis Targeting RORγ: From Bench to Skin.

Authors:  Susan H Smith; Carlos E Peredo; Yukimasa Takeda; Thi Bui; Jessica Neil; David Rickard; Elizabeth Millerman; Jean-Philippe Therrien; Edwige Nicodeme; Jean-Marie Brusq; Veronique Birault; Fabrice Viviani; Hans Hofland; Anton M Jetten; Javier Cote-Sierra
Journal:  PLoS One       Date:  2016-02-12       Impact factor: 3.240
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