321351-00-2

Usage

Uses

EO 1428 is a p38 MAP kinase inhibitor with high antiinflammatory activity.

Biological Activity

Selective inhibitor of p38 α and p38 β 2 that displays no activity at p38 γ , p38 δ , ERK1/2 and JNK1. Inhibits production of inflammatory cytokines including IL-8, TNF- α , IL-6, IL-1 β and IL-10 (IC 50 values are 4, 5, 17, 30 and 74 nM respectively). Displays anti-inflammatory activity in murine models of acute and chronic dermatitis.

InChI:InChI=1/C20H16BrClN2O/c1-12-4-2-3-5-15(12)20(25)16-8-7-14(11-17(16)22)24-19-9-6-13(21)10-18(19)23/h2-11,24H,23H2,1H3

Upstream product

• 321378-18-1 {4-[(4-bromo-2-nitrophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone 
• 344459-21-8 (2-chloro-4-nitrophenyl)(2-methylphenyl)methanone 
• 210967-34-3 (4-amino-2-chlorophenyl)(2-methylphenyl)methanone 
• 7073-36-1 2-chloro-4-nitrobenzoyl chloride 
• 99-60-5 2-chloro-4-nitrobenzoic acid 

Downstream Products

• 500875-54-7 N-[2-({3-Chloro-4-[(2-methylphenyl)carbonyl]phenyl}amino)benzyl]-2,2,2-trifluoroethanesulfonamide 
• 500875-55-8 N-[5-Bromo-2-({3-chloro-4-[(2-methylphenyl)carbonyl]phenyl}amino)phenyl]-2,2,2-trifluoroethanesulfonamide 
• 500875-51-4 diethyl 2-{[5-bromo-2-({3-chloro-4-[(2-methylphenyl)carbonyl]phenyl}amino)phenyl]amino}-2-oxoethylphosphonate 

Relevant academic research and scientific papers

Synthesis and Structure-Activity Relationship of Aminobenzophenones. A Novel Class of p38 MAP Kinase Inhibitors with High Antiinflammatory Activity

We wish to report the synthesis and structure-activity relationship (SAR) of a series of 4-aminobenzophenones, as a novel compound class with high antiinflammatory activity. Our initial lead, {4-[(2-aminophenyl)amino]phenyl}(phenyl)methanone (3), was systematically optimized and resulted in compounds that potently inhibited the release of the proinflammatory cytokines IL-1β and TNF-α in human peripheral blood mononuclear cells stimulated by LPS. One of the most potent compounds, among others, was {4-[(2-aminophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone (45) with IC50 values of 14 and 6 nM for the inhibition of IL-1β and TNF-α, respectively. Furthermore, we found these types of compounds to be potent and selective p38 MAP kinase inhibitors, e.g. 45 had an IC50 value of 10 nM. Molecular modeling was used to rationalize our SAR data and to propose a model for the interaction of compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond between the carbonyl group of the benzophenone and the NH of Met-109, positioning ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects were demonstrated in two murine models of dermatitis after topical application (oxazolone and TPA model).

Aminobenzophenones

The present invention relates to compounds of formula I wherein R1represents one or more, similar or different substituents; R2represents hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylthio, or cyano; R3represents one or more, similar or different substituents; and R6represents hydrogen or methyl; and salts thereof with pharmaceutically acceptable acids, hydrates, and solvates, and to the use of compounds of the general formula II in which formula R1and R2independently represent one or more, similar or different substituents; R3represents hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, alkyl, alkoxy, alkylthio, alkylamino, or alkoxycarbonyl, phenyl, cyano, carboxy, or carbamoyl; R4, R5and R6represent independently hydrogen, trifluoromethyl, alkyl, carbamoyl, alkoxycarbonyl, or alkaloyl; x represents oxygen, N—OH, and N—O-alkyl, dialkoxy, cyclic dialkoxy, dialkylthio, or cyclic dialkylthio, and salts thereof with pharmaceutically acceptable, non-toxic acids.

Dermal anti-inflammatory composition

A pharmaceutical composition for dermal application comprises a lipophilic anti-inflammatory compound and a pharmaceutically acceptable vehicle comprising a lipophilic excipient capable of solubilizing the anti-inflammatory compound and targeting said compound to the pilosebaceous ducts on application of the composition on the skin. The composition may be used in the treatment of dermal inflammatory conditions, in particular acne.