1198765-15-9

Upstream product

• 1198765-14-8 N-(3-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-cyclopropyl-2-methylbenzamide 
• 68-12-2 N,N-dimethyl-formamide 
• 1147531-02-9 ((2-bromo-6-nitrobenzyl)oxy)(tert-butyl)dimethylsilane 
• 1147531-04-1 3-bromo-2-[[tert-butyl(dimethyl)silyl]oxymethyl] aniline 
• 68837-59-2 4-bromo-2-methylbenzoic acid 
• 99548-55-7 4-bromo-2-methyl-benzoic acid methyl ester 
• 909698-09-5 methyl 4-cyclopropyl-2-methylbenzoate 
• 909698-10-8 4-cyclopropyl-2-methylbenzoic acid 
• 1198765-13-7 4-cyclopropyl-2-methylbenzoyl chloride 
• 861106-91-4 (2-bromo-6-nitro-phenyl)-methanol 
• 18162-48-6 tert-butyldimethylsilyl chloride 

Downstream Products

• 1198765-16-0 2-[3-bromo-2-(tert-butyldimethylsilanyloxymethyl)phenyl]-6-cyclopropyl-2H-isoquinolin-1-one 

Relevant academic research and scientific papers

Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis

Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) (J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.

Inhibitors of Bruton's Tyrosine Kinase

This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y1, Y2, Y2′, Y3, Y4, Y5, m, and n 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 further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.