303133-89-3

Upstream product

• 96-98-0 4-methyl-3-nitrobenzoic acid 

Downstream Products

• 623155-19-1 3-amino-N-cyclopropyl-4-methylbenzamide 
• 623155-66-8 3-amino-N-cyclopropyl-4-methyl-benzamide hydrochloride 
• 851847-00-2 5-fluoro-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitrobenzamide 
• 1383111-04-3 C₂₃H₂₇N₅O₄ 
• 1383111-14-5 C₂₃H₂₉N₅O₂ 
• 948842-74-8 iodomethyl cyclopropyl(4-methyl-3-nitrobenzoyl)carbamate 
• 948842-76-0 (bis(benzyloxy)phosphoryloxy)methylcyclopropyl(4-methyl-3-nitrobenzoyl)carbamate 
• 948842-78-2 (bis(benzyloxy)phosphoryloxy)methyl-3-amino-4-methylbenzoyl(cyclopropyl)-carbamate 
• 948842-80-6 (bis(benzyloxy)phosphoryloxy)methylcyclopropyl(4-methyl-3-(5-methyl-6-(propylcarbamoyl)pyrrolo[1,2-f][1,2,4]triazin-4-ylamino)benzoyl)carbamate 
• 948842-87-3 (S)-(cyclopropyl(4-methyl-3-nitrobenzoyl)carbamoyloxy)methyl 2-(benzyloxycarbonyl)propanoate 
• 948842-88-4 (S)-((3-amino-4-methylbenzoyl)(cyclopropyl)carbamoyloxy)methyl 2-(benzyloxycarbonyl)propanoate 
• 948842-98-6 Chloromethyl 3-amino-4-methylbenzoyl(cyclopropyl)carbamate 
• 948842-99-7 chloromethyl cyclopropyl(4-methyl-3-(5-methyl-6-(propylcarbamoyl)pyrrolo[1,2-f][1,2,4]triazin-4-ylamino)benzoyl)carbamate 
• 948842-89-5 (S)-(cyclopropyl(4-methyl-3-(5-methyl-6-(propylcarbamoyl)pyrrolo[1,2-f][1,2,4]-triazin-4-ylamino)benzoyl)carbamoyloxy)methyl 2-(benzyloxycarbonyl)propanoate 

Relevant academic research and scientific papers

Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine

We recently reported 1a (skepinone-L) as a type I p38α MAP kinase inhibitor with high potency and excellent selectivity in vitro and in vivo. However, as a type I inhibitor, it is entirely ATP-competitive and shows just a moderate residence time. Thus, the scope was to develop a new class of advanced compounds maintaining the structural binding features of skepinone-L scaffold like inducing a glycine flip at the hinge region and occupying both hydrophobic regions I and II. Extending this scaffold with suitable residues resulted in an interference with the kinase's R-Spine. By synthesizing 69 compounds, we could significantly prolong the target residence time with one example to 3663 s, along with an excellent selectivity score of 0.006 and an outstanding potency of 1.0 nM. This new binding mode was validated by cocrystallization, showing all binding interactions typifying type I1/2 binding. Moreover, microsomal studies showed convenient metabolic stability of the most potent, herein reported representatives.

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.