267416-80-8Relevant articles and documents
Structural Development of Salicylanilide-Based SPAK Inhibitors as Candidate Antihypertensive Agents
Fujii, Shinya,Kikuchi, Eriko,Suzuyama, Honoka,Watanabe, Yuko,Ishigami-Yuasa, Mari,Masuno, Hiroyuki,Mori, Takayasu,Isobe, Kiyoshi,Uchida, Shinichi,Kagechika, Hiroyuki
supporting information, p. 2817 - 2822 (2021/07/12)
Hypertension is an important target for drug discovery. We have focused on the with-no-lysine kinase (WNK)-oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related proline-alanine-rich protein kinase (SPAK)-NaCl cotransporter (NCC) signal cascade as a potential target, and we previously developed a screening system for inhibitors of WNK-OSR1/SPAK-NCC signaling. Herein we used this system to examine the structure-activity relationship (SAR) of salicylanilide derivatives as SPAK kinase inhibitors. Structural design and development based on our previous hit compound, aryloxybenzanilide derivative 2, and the veterinary anthelmintic closantel (3) led to the discovery of compound 10 a as a potent SPAK inhibitor with reduced toxicity. Compound 10 a decreased the phosphorylation level of NCC in mouse kidney in vivo, and appears to be a promising lead compound for a new class of antihypertensive drugs.
HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF EPILEPSY
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Paragraph 0135; 0143; 0144, (2020/06/19)
The present invention provides a novel heterocyclic compound represented by Formula [I] and a salt thereof: wherein the symbols are as defined in the specification, which is useful for treating, preventing and/or diagnosing seizure and the like in disease involving epileptic seizure or convulsive seizure (including multiple drug resistant seizure, refractory seizure, acute symptomatic seizure, febrile seizure and status epilepticus), as well as a medical use therefor.
INHIBITORS OF BRUTON'S TYROSINE KINASE
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Page/Page column 48; 51; 69, (2015/06/25)
This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.