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Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors.
Wang, Yonghui; Cai, Wei; Zhang, Guifeng; Yang, Ting; Liu, Qian; Cheng, Yaobang; Zhou, Ling; Ma, Yingli; Cheng, Ziqiang; Lu, Sijie; Zhao, Yong-Gang; Zhang, Wei; Xiang, Zhijun; Wang, Shuai; Yang, Liuqing; Wu, Qianqian; Orband-Miller, Lisa A; Xu, Yan; Zhang, Jing; Gao, Ruina; Huxdorf, Melanie; Xiang, Jia-Ning; Zhong, Zhong; Elliott, John D; Leung, Stewart; Lin, Xichen.
Afiliação
  • Wang Y; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China. Electronic address: wang.2.yonghui@gmail.com.
  • Cai W; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhang G; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Yang T; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Liu Q; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Cheng Y; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhou L; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Ma Y; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Cheng Z; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Lu S; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhao YG; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhang W; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Xiang Z; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Wang S; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Yang L; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Wu Q; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Orband-Miller LA; Research and Development, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
  • Xu Y; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhang J; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Gao R; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Huxdorf M; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Xiang JN; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Zhong Z; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Elliott JD; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Leung S; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
  • Lin X; Research and Development, GlaxoSmithKline, No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.
Bioorg Med Chem ; 22(2): 692-702, 2014 Jan 15.
Article em En | MEDLINE | ID: mdl-24388993
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite / Encefalomielite Autoimune Experimental / Descoberta de Drogas / Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares / Amidas Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite / Encefalomielite Autoimune Experimental / Descoberta de Drogas / Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares / Amidas Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Ano de publicação: 2014 Tipo de documento: Article