1616291-01-0

Upstream product

• 60166-43-0 1,4-dimethyl-1H-[1,2,3]triazole 
• 1616290-97-1 5-amino-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one 
• 1616290-95-9 5-amino-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-iodo-3,4-dihydroisoquinolin-1(2H)-one 
• 1616290-93-7 5-amino-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-iodo-3,4-dihydroisoquinolin-1(2H)-one 
• 1616290-91-5 5-amino-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one 
• 1616290-89-1 7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-nitroisoquinolin-1(2H)-one 
• 1368065-77-3 7-bromo-5-nitroisoquinolin-1(2H)-one 
• 1616290-87-9 7-bromo-5-nitro-1H-isochromene-1-one 
• 220514-28-3 5-bromo-2-methyl-3-nitrobenzoic acid methyl ester 
• 100-44-7 benzyl chloride 
• 1303445-99-9 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine 
• 1616290-99-3 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one 
• 1306439-42-8 [2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methanol 
• 721959-71-3 2-(benzyloxy)-4,6-dimethylpyridine-3-carbaldehyde 

Relevant academic research and scientific papers

Design and Characterization of a Pyridone-Containing EZH2 Inhibitor Phosphate Prodrug

A pyridone-derived phosphate prodrug of an enhancer of zeste homolog 2 (EZH2) inhibitor was designed and synthesized to improve the inhibitor's aqueous solubility. This prodrug (compound 5) was profiled in pharmacokinetic experiments to assess its ability to deliver the corresponding parent compound (compound 2) to animals in vivo following oral administration. Results from these studies showed that the prodrug was efficiently converted to its parent compound in vivo. In separate experiments, the prodrug demonstrated impressive in vivo tumor growth inhibition in a diffuse large B-cell lymphoma Karpas-422 cell line-derived xenograft model. The described prodrug strategy is expected to be generally applicable to poorly soluble pyridone-containing EZH2 inhibitors and provides a new option to enable such compounds to achieve sufficiently high exposures in vivo.

ARYL AND HETEROARYL FUSED LACTAMS

This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.