- BIARYL UREA DERIVATIVE OR SALT THEREOF, AND MANUFACTURING AND APPLICATION OF SAME
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The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.
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Paragraph 0054
(2019/05/10)
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- Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors
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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.
- Wang, Yonghui,Cai, Wei,Cheng, Yaobang,Yang, Ting,Liu, Qian,Zhang, Guifeng,Meng, Qinghua,Han, Fangbin,Huang, Yafei,Zhou, Ling,Xiang, Zhijun,Zhao, Yong-Gang,Xu, Yan,Cheng, Ziqiang,Lu, Sijie,Wu, Qianqian,Xiang, Jia-Ning,Elliott, John D.,Leung, Stewart,Ren, Feng,Lin, Xichen
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supporting information
p. 787 - 792
(2015/07/15)
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- 1-Aryl-3,3-dialkyltriazenes: A convenient synthesis from dry arenediazonium o-benzenedisulfonimides - A high yield break down to the starting dry salts and efficient conversions to aryl iodides, bromides and chlorides
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This research comprises three parts. The first part regards the synthesis of 1-aryl-3,3-dialkyltriazenes 3 by reaction of dry arenediazonium o-benzenedisulfonimides 1, also coming from weakly basic aromatic amines with dimethylamine or diethylamine in aqueous solution at 0-5 °C. Yields were usually greater than 90% and there was the possibility of recovering the o-benzenedisulfonimide (5), which could be reused to prepare the salts 1. In the second part it was demonstrated that there is the possibility of reconverting the triazenes 3 into the starting stable dry salts 1 by using 5 as acid. The reactions were carried out in glacial acetic acid at 50-55 °C and normally afforded salts 1 in yields of around 90-99%. The third part concerns the setting up of two procedures for the conversion of 3 to aryl iodides 9, bromides 10 and chlorides 11. Procedure A used the corresponding aqueous hydrogen halides in acetonitrile at r.t. or 60 °C, sometimes in the presence of aqueous HBF4, sometimes Cu powder (25 examples, yields 65%-88%). Procedure B usually used anhydrous methanesulfonic acid and tetraalkylammonium halides in anhydrous acetonitrile at temperatures varying from r.t. to 80 °C, sometimes in the presence of Cu (16 examples, yields 65-88%).
- Barbero,Degani,Diulgheroff,Dughera,Fochi
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p. 2180 - 2190
(2007/10/03)
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- Russuphelin A, a new cytotoxic substance from the mushroom Russula subnigricans HONGO
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A new cytotoxic substance, designated russuphelin A (1), has been isolated from the mushroom Russula subnigricans HONGO (Basidiomycetes). The structure was elucidated as 2,6-bis(2,6-dichloro-4-hydroxyphenyloxy)-1,4-dimethoxy-benzene on the basis of spectr
- Takahashi,Agatsuma,Matsuda,Ohta,Nunozawa,Endo,Nozoe
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p. 3185 - 3188
(2007/10/02)
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