648923-55-1

Upstream product

• 321-14-2 5-chloro-2-hydroxybenzoic acid 
• 85068-29-7 3,5-bis-trifluoromethylbenzylamine 

Relevant academic research and scientific papers

Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists

Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (1, IC50 0.0192 μM) and N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide (14, IC50 0.0231 μM), displayed >500-fold selectivity versus P2X2 and P2X3, and 10-fold selectivity versus P2X4 and P2X7 receptors, and inhibited collagen-induced platelet aggregation. They behaved as negative allosteric modulators, and molecular modeling studies suggested an extracellular binding site. Besides selective P2X1 antagonists, compounds with ancillary P2X4 and/or P2X7 receptor inhibition were discovered. These compounds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.

2-HYDROXYARYLAMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a 2-hydroxyarylamide derivative or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. The 2-hydroxyarylamide derivative prepared by the present invention is excellent in the inhibition of the activity of TMPRSS4 serine protease and the suppression of the infiltration of TMPRSS4-expressed cancer cells, and thus can be useful as a composition for preventing or treating cancer by inhibiting TMPRSS4 over-expressed in cancer cells, particularly, colorectal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, or stomach cancer cells.

Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors

TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4.

Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling

A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics.