851847-00-2

Upstream product

• 10397-30-5 4-methyl-3-nitrobenzoyl chloride 
• 303133-89-3 N-cyclopropyl-4-methyl-3-nitrobenzamide 
• 623155-19-1 3-amino-N-cyclopropyl-4-methylbenzamide 
• 320-98-9 5-fluoro-2-nitrobenzoic acid 

Downstream Products

• 851847-58-0 tert-butyl 4-{3-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]-4-nitrophenoxy}piperidine-1-carboxylate 
• 1383111-04-3 C₂₃H₂₇N₅O₄ 
• 1383111-14-5 C₂₃H₂₉N₅O₂ 
• 851847-78-4 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-[(2-methylprop-2-en-1-yl)oxy]-2-nitrobenzamide 
• 851847-65-9 tert-butyl 3-{3-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]-4-nitrophenoxy}pyrrolidine-1-carboxylate 
• 851847-41-1 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-morpholin-4-yl-2-nitrobenzamide 

Relevant academic research and scientific papers

The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4- oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases

A novel, potent and selective quinazolinone series of inhibitors of p38α MAP kinase has been identified. Modifications designed to address the issues of poor aqueous solubility and high plasma protein binding as well as embedded aniline functionalities resulted in the identification of a clinical candidate N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin- 3(4H)-yl]benzamide (AZD6703). Optimisation was guided by understanding of the binding modes from X-ray crystallographic studies which showed a switch from DFG 'out' to DFG 'in' as the inhibitor size was reduced to improve overall properties.

AMIDE DERIVATIVES

The invention concerns a compound of the Formula (I) wherein m is 0-2 and each R1 is a group such as hydroxy, halogeno, trifluoromethyl heterocyclyl and heterocyclyloxy; R2 is halogeno, trifluoromethyl or (1-6C)alkyl; R3 is hydrogen, halogeno or (1-6C)alkyl; and R4 is (3-6C)cycloalkyl;or pharmaceutically-acceptable salts thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical condions mediated by cytokines.