Some Analogs of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid: Synthesis and Antiinflammatory Activity

Abstract

Analogs of 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (I, flobufen), containing a double bond (II, IV, V, VII, VIII) or a methyl group in position 3 (VI) were prepared. Their antiinflammatory activity was evaluated and compared with that of flobufen. None of the mentioned analogs reached the activity of the standard. Isomerization of the unsaturated derivatives is connected with a shift of the double bond, Z-E transformation or lactonization. Reaction conditions and spectra of the compounds prepared are described.

CIAT with simultaneous epimerization at two stereocenters. Synthesis of substituted β-methyl-α-homophenylalanines

“…25 The Friedel-Crafts reaction of aromatics with citraconic anhydride exhibits low regioselectivity and stereoselectivity and the formation of the (Z)stereomer in the form of cyclic tautomeric lactone was observed. 26 In our optimized conditions the desired (E)-stereomers 2a-c were prepared in yields ranging from 51 up to 73% and in E : Z ratio more than 81 : 19, which can be increased up to 96 : 4 by one crystallization. 4-Methoxy substituted propiophenones 2b,c were prepared by highly regioselective LiClO 4 -catalyzed acylation.…”

Crystal structure of 4-(2',4'-difluorobiphenyl-4-yl)-2-methylbutanoic acid, F2C16H15COOH, deoxoflobufen

“…The structure is related to flobufen [ 1,2], an anti-inflammatory a>-biphenyl-co-oxoalkanoic acid. The basic structural motif is created by pairs of deoxoflobufen molecules lying with their long axes nearly parallel in a head-to-head arrangement.…”

“…Source of material 4-(2',4'-Difluorobiphenyl-4-yl)-2-methylene-4-oxobutanoic acid (20 g) [1] was dissolved in acetic acid (100 ml), Pd/C was added (10 % Pd/C, 50 % H20,8 g), and the reaction mixture was hydrogenated at ambient pressure under vigorous stirring on magnetic stirrer and heating at 60 °C. After 5 h, Pd/C was filtered off and the solution was evaporated on rotary vacuum evaporator.…”

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

“…One of these NSAIDs is flobufen, 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (F). F is one of the outcomes of the study of the relationship between arylalkanoic acids and living organisms towards the end of the 1980's [4,5]. F, together with fenbufen [6], belongs to the group of aryloxobutyric acids, which are structurally related to arylpropionic acids (e.g.…”