19750-02-8Relevant articles and documents
MACROCYCLIC SULFONYLAMIDE DERIVATIVES USEFUL AS NLRP3 INHIBITORS
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Page/Page column 164, (2021/02/26)
The present invention relates to macrocyclic compounds, such as macrocyclic sulfonyl amides. The present invention further relates to associated salts, solvates, prodrugs and pharmaceutical compositions, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.
Design and synthesis of Imidazo[1,2-b]pyridazine IRAK4 inhibitors for the treatment of mutant MYD88 L265P diffuse large B-cell lymphoma
Chen, Yun,Bai, Gang,Ning, Yi,Cai, Shi,Zhang, Tao,Song, Peiran,Zhou, Jinpei,Duan, Wenhu,Ding, Jian,Xie, Hua,Zhang, Huibin
supporting information, (2020/02/04)
Harboring MYD88 L265P mutation triggers tumors growth through the activation of NF-κB by interleukin-1 receptor associated kinase 4 (IRAK4) in diffuse large B-cell lymphoma (DLBCL), highlighting IRAK4 as a therapeutic target for tumors driven by aberrant MYD88 signaling. Herein, we report the design, synthesis, and structure?activity relationships of imidazo[1,2-b]pyridazines as potent IRAK4 inhibitors. The representative compound 5 exhibited excellent IRAK4 potency (IRAK4 IC50 = 1.3 nM) and favorable kinase selectivity profile. It demonstrated cellular selectivity for activated B cell–like (ABC) subtype DLBCL with MYD88 L265P mutation in cytotoxicity assay. The kinase inhibitory efficiency of compound 5 was further validated by Western blot analysis of phosphorylation of IRAK4 and downstream signaling in OCI-LY10 and TMD8 cells. Besides, combination of compound 5 and BTK inhibitor ibrutinib synergistically reduced the viability of TMD8 cells. These results indicated that compound 5 could be a promising IRAK4 inhibitor for the treatment of mutant MYD88 DLBCL.
Synthetic method of pesticide intermediate pyrazole-4-ethyl formate
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, (2017/06/02)
The invention discloses a synthetic method of pesticide intermediate pyrazole-4-ethyl formate. The method comprises the following steps: 1) ethyl cyanoacetate and triethyl orthoformate are placed in a flask, acetic anhydride is added for a reaction, an oil pump is used for performing underpressure distillation to obtain efhylene efhoxymethylene cyanoncetata; 2) efhylene efhoxymethylene cyanoncetata is dissolved in ethanol, hydrazine hydrate is added drop by drop, a solvent is used for underpressure distillation to obtain 3-amino-pyrazoles-4-ethyl formate; and 3) adding pyrazoles-4-ethyl formate and glacial acetic acid are added in a reaction bottle, hydrochloric acid is added drop by drop, a sodium nitrite solution is added drop by drop, after the reaction, ethanol is added for backflow and vacuum concentration, dichloromethane and water are added for stirring and layering, and an organic layer is re-crystallized to obtain the finished product. By employing ester condensation, cyclization and deamination reactions, the preparation technology is simple, and the product is easily purified, production cost is low, and the method is suitable for large-scale industrial production.