Add time:09/05/2019 Source:sciencedirect.com
N-Benzyl-N-(4-phenoxyphenyl)benzenesulfonamide derivatives were developed as a novel class of nonsteroidal glucocorticoid receptor (GR) modulators, which are promising drug candidates for treating immune-related disorders. Focusing on the similarity of the GR and progesterone receptor (PR) ligand-binding domain (LBD) structures, we adopted our recently developed PR antagonist 10 as a lead compound and synthesized a series of derivatives. We found that the N-(4-phenoxyphenyl)benzenesulfonamide skeleton serves as a versatile scaffold for GR antagonists. Among them, 4-cyano derivative 14m was the most potent, with an IC50 value of 1.43 μM for GR. This compound showed good selectivity for GR; it retained relatively weak antagonistic activity toward PR (IC50 for PR: 8.00 μM; 250-fold less potent than 10), but showed no activity toward AR, ERα or ERβ. Interestingly, the 4-amino derivative 15a exhibited transrepression activity toward NF-κB in addition to GR-antagonistic activity, whereas 14m did not. The structure-activity relationship for transrepression was different from that for GR-antagonistic activity. Computational docking simulations suggested that 15a might bind to the ligand-binding pocket of GR in a different manner from 14m. These findings open up new possibilities for developing novel nonsteroidal GR modulators with distinctive activity profiles.
We also recommend Trading Suppliers and Manufacturers of N-(2-methyl-5-nitro-phenyl)benzenesulfonamide (cas 121-77-7). Pls Click Website Link as below: cas 121-77-7 suppliers
About|Contact|Cas|Product Name|Molecular|Country|Encyclopedia
Message|New Cas|MSDS|Service|Advertisement|CAS DataBase|Article Data|Manufacturers | Chemical Catalog
©2008 LookChem.com,License: ICP
NO.:Zhejiang16009103
complaints:service@lookchem.com Desktop View