1211580-90-3

Basic information

• Product Name: N-methoxy-N,2-dimethylisonicotinamide
• Synonyms: N-methoxy-N,2-dimethylisonicotinamide
• CAS NO: 1211580-90-3
• Molecular Weight: 180.206
• Mol File: 1211580-90-3.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: N-methoxy-N,2-dimethylisonicotinamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-methoxy-N,2-dimethylisonicotinamide(1211580-90-3)
• EPA Substance Registry System: N-methoxy-N,2-dimethylisonicotinamide(1211580-90-3)

Safety Data

• Hazardous Substances Data: 1211580-90-3(Hazardous Substances Data)

Upstream product

• 4021-11-8 2-methylisonicotinic acid 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 

Downstream Products

• 2732-28-7 1-(2-methylpyridin-4-yl)ethan-1-one 

Relevant articles and documents

Structure-activity relationships for unit C pyridyl analogues of the tuberculosis drug bedaquiline

The ATP-synthase inhibitor bedaquiline is effective against drug-resistant tuberculosis but is extremely lipophilic (clogP 7.25) with a very long plasma half-life. Additionally, inhibition of potassium current through the cardiac hERG channel by bedaquiline, is associated with prolongation of the QT interval, necessitating cardiovascular monitoring. Analogues were prepared where the naphthalene C-unit was replaced with substituted pyridines to produce compounds with reduced lipophilicity, anticipating a reduction in half-life. While there was a direct correlation between in vitro inhibitory activity against M. tuberculosis (MIC90) and compound lipophilicity, potency only fell off sharply below a clogP of about 4.0, providing a useful lower bound for analogue design. The bulk of the compounds remained potent inhibitors of the hERG potassium channel, with notable exceptions where IC50 values were at least 5-fold higher than that of bedaquiline. Many of the compounds had desirably higher rates of clearance than bedaquiline, but this was associated with lower plasma exposures in mice, and similar or higher MICs resulted in lower AUC/MIC ratios than bedaquiline for most compounds. The two compounds with lower potency against hERG exhibited similar clearance to bedaquiline and excellent efficacy in vivo, suggesting further exploration of C-ring pyridyls is worthwhile.

HUMAN PLASMA KALLIKREIN INHIBITORS

Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

COMPOUNDS AND METHODS

The present invention relates to no vel retinoid-related orphan receptor gamma (RQRy) modulators and their use in the treatment of diseases mediated by RORy.