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Wang Y, Cai W, Cheng Y, et al. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS Med Chem Lett. 2015;6(7):787-92doi: 10.1021/acsmedchemlett.5b00122.
Wang, Y., Cai, W., Cheng, Y., Yang, T., Liu, Q., Zhang, G., Meng, Q., Han, F., Huang, Y., Zhou, L., Xiang, Z., Zhao, Y. G., Xu, Y., Cheng, Z., Lu, S., Wu, Q., Xiang, J. N., Elliott, J. D., Leung, S., Ren, F., & Lin, X. (2015). Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS medicinal chemistry letters, 6(7), 787-92. https://doi.org/10.1021/acsmedchemlett.5b00122
Wang, Yonghui, et al. "Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors." ACS medicinal chemistry letters vol. 6,7 (2015): 787-92. doi: https://doi.org/10.1021/acsmedchemlett.5b00122
Wang Y, Cai W, Cheng Y, Yang T, Liu Q, Zhang G, Meng Q, Han F, Huang Y, Zhou L, Xiang Z, Zhao YG, Xu Y, Cheng Z, Lu S, Wu Q, Xiang JN, Elliott JD, Leung S, Ren F, Lin X. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS Med Chem Lett. 2015 May 26;6(7):787-92. doi: 10.1021/acsmedchemlett.5b00122. eCollection 2015 Jul 09. PMID: 26191367; PMCID: PMC4499822.
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ACS Med Chem Lett. 2015 May 26;6(7):787-92. doi: 10.1021/acsmedchemlett.5b00122. eCollection 2015 Jul 09.

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

ACS medicinal chemistry letters

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

Affiliations

  1. School of Pharmacy, Fudan University , 826 Zhangheng Road, Pudong, Shanghai 201203, China.
  2. Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.

PMID: 26191367 PMCID: PMC4499822 DOI: 10.1021/acsmedchemlett.5b00122

Abstract

A novel series of biaryl amides was identified as RORγt inhibitors through core replacement of a starting hit 1. Structure-activity relationship exploration on the biaryl moiety led to discovery of potent RORγt inhibitors with good oral bioavailability and CNS penetration. Compounds 9a and 9g demonstrated excellent in vivo efficacy in EAE mice dose dependently with once daily oral administration.

Keywords: EAE; RORγt inhibitor; Th17 cell differentiation; biaryl amides; multiple sclerosis

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