1214328-96-7Relevant articles and documents
HPK1 ANTAGONISTS AND USES THEREOF
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Paragraph 0853; 0854, (2021/03/19)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.
Discovery of [1,2,4]Triazolo[1,5- a]pyridine Derivatives as Potent and Orally Bioavailable RORγt Inverse Agonists
Nakajima, Ryota,Oono, Hiroyuki,Sugiyama, Sakae,Matsueda, Yohei,Ida, Tomohide,Kakuda, Shinji,Hirata, Jun,Baba, Atsushi,Makino, Akito,Matsuyama, Ryo,White, Ryan D.,Wurz, Ryan P.,Shin, Youngsook,Min, Xiaoshan,Guzman-Perez, Angel,Wang, Zhulun,Symons, Antony,Singh, Sanjay K.,Mothe, Srinivasa Reddy,Belyakov, Sergei,Chakrabarti, Anjan,Shuto, Satoshi
supporting information, p. 528 - 534 (2020/03/13)
The retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with 1a, an analogue of the known piperazine RORγt inverse agonist 1, triazolopyridine derivatives of 1 were designed and synthesized, and analogue 3a was found to be a potent RORγt inverse agonist. Structure-activity relationship studies on 3a, focusing on the treatment of its metabolically unstable cyclopentyl ring and the central piperazine core, led to a novel analogue, namely, 6-methyl-N-(7-methyl-8-(((2S,4S)-2-methyl-1-(4,4,4-trifluoro-3-(trifluoromethyl)butanoyl)piperidin-4-yl)oxy)[1,2,4]triazolo[1,5-a]pyridin-6-yl)nicotinamide (5a), which exhibited strong RORγt inhibitory activity and a favorable pharmacokinetic profile. Moreover, the in vitro and in vivo evaluation of 5a in a human whole-blood assay and a mouse IL-18/23-induced cytokine expression model revealed its robust and dose-dependent inhibitory effect on IL-17A production.
SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
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Paragraph 0233, (2019/10/15)
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.