1201657-09-1Relevant articles and documents
Synthesis and biological evaluation of 4-(pyridine-4-oxy)-3-(tetrahydro-2H-pyran-4-yl)-pyrazole derivatives as novel, potent of ALK5 receptor inhibitors
Wang, Hai,Wang, Xiaowei,Wang, Zhenwei,Yu, Zhuangzhuang,Zhang, Yan,Zhao, Liwen
supporting information, (2022/02/16)
The transforming growth factor type β receptor I (TGF-β R1, also known as activin-like kinase 5 or ALK5) plays a significant role in the pathogenesis of multiple diseases such as malignant tumors and tissue fibrosis. Specific inhibition of ALK5 provides a novel method for controlling the development of cancers and fibrotic diseases. Herein, a novel series of 4-(pyridine-4-oxy)-3-(tetrahydro-2H-pyran-4-yl)-pyrazole derivatives was synthesized and identified as ALK5 inhibitors. Among them, compound 8h inhibited ALK5 autophosphorylation and NIH3T3 cell activity with IC50 values of 25 nM and 74.6 nM, respectively. Compound 8h also showed favorable pharmacokinetic profile and ameliorated hERG inhibition. More importantly, 30 mg/kg oral administration of 8h could significantly induce tumour growth inhibition in CT26 xenograft model without obvious toxicity.
PI3 KINASE INHIBITORS AND USES THEREOF
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Paragraph 00221, (2019/02/15)
Described herein are PI3 Kinase inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer, cardiovascular diseases, and inflammatory diseases.
SOLID FORMS OF ISOQUINOLINONE DERIVATIVES, PROCESS OF MAKING, COMPOSITIONS COMPRISING, AND METHODS OF USING THE SAME
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Paragraph 001136; 001138-001142; 001144-001148; 001155, (2017/04/11)
Solid forms of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphic forms, cocrystals, and amorphous forms thereof, and pharmaceutical compositions thereof.