34599-42-3Relevant articles and documents
COMPOUND INHIBITING YAP-TEAD BINDING, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER, COMPRISING COMPOUND AS ACTIVE INGREDIENT
-
Paragraph 0138-0139, (2021/09/24)
The present invention relates to a compound which inhibits the binding of Yes associated protein (YAP) and transcriptional enhancer associate domain (TEAD), a prodrug of same, a hydrate of same, a solvate of same or a pharmaceutically acceptable salt of same, and a composition comprising same as an active ingredient, the compound according to the present invention being able to be applied as an inhibitor which can directly inhibit YAP-TEAD binding in the Hippo pathway which plays a crucial role in the occurrence of cancer.
Preparation method of 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative
-
Paragraph 0070-0072, (2019/08/06)
The invention provides a preparation method of 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative. The preparation method is characterized by comprising thefollowing steps: S1, dissolving 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon and subgroup metal nitrate in an organic solvent, performing a nitration reaction under 10-60 DEG Cfor 4-10 h, and then monitoring by TLC (Thin layer chromatography) till a raw material point disappears to finish the reaction; S2, cooling a product obtained in S1 to room temperature, performing suction filtration, washing filter cake with 5-10 mL of H2O and anhydrous C2H5OH separately, and performing vacuum drying to obtain the 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative. According to the preparation method of the 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative, the product yield is 93%-96%; theproduct purity is 98%-99.5%; compared with the prior art, the preparation method has the characteristics of high product yield, high purity, low cost and simple process, and is easy to industrialize.
Discovery of Benzo[ cd]indol-2(1 H)-ones and Pyrrolo[4,3,2- de]quinolin-2(1 H)-ones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain with Potential High Efficiency against Acute Gouty Arthritis
Jiang, Fei,Hu, Qinghua,Zhang, Zhimin,Li, Hongmei,Li, Huili,Zhang, Dewei,Li, Hanwen,Ma, Yu,Xu, Jingjing,Chen, Haifang,Cui, Yong,Zhi, Yanle,Zhang, Yanmin,Xu, Junyu,Zhu, Jiapeng,Lu, Tao,Chen, Yadong
, p. 11080 - 11107 (2019/12/24)
The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.
