Arylalkyl Ketones, Benzophenones, Desoxybenzoins and Chalcones Inhibit TNF‐α Induced Expression of ICAM‐1: Structure‐Activity Analysis

Abstract

The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.

Total Synthesis of Evelynin B and Taccabulin D

“…16 Finally, enone 8 was hydrogenated in the presence of Pd on carbon (10%) to afford diphenol 9, which was used for next step without further purification. 17 Oxidation of 9 by PCC in DCM successfully provided natural product evelynin B (1) with 73% yield as a yellow solid in two steps. 18 The total synthesis of taccabulin D is similar to that of evelynin B (Scheme 2).…”

Concise Total Synthesis of 1,3-Diphenylpropane Derivatives Griffithanes A, B and F

“…[17][18][19][20][21][22][23] The key intermediates 1,3-diphenylpropenones (chalcones) 14-16 were synthesised by Claisen-Schmidt condensation of acetophenones 6 and 8 with aldehydes 7, 10 and 13 in 75-85% yields. 10,[24][25][26] The structures of 14 and 16 were confirmed by X-ray crystallography (Fig. 2) JOURNAL OF CHEMICAL RESEARCH 2015 417 diphenylpropanes 1-3 by a one-step reduction of compounds 14-16, but did not succeed.…”

“…1 Structures bearing the diarylpropane motif have a diverse range of biological properties including antiinflammatory, 2, 3 antifungal, 4 anti-vascular, 5 anti-adipogenic, 6 anti-hCNT3 (human concentrative nucleoside transporter 3), 7 anti-proliferative, 8 inhibiting aromatase, 9 inducing TNF-α expression, 10 inhibiting DOPA decarboxylase, 11 and antitubercular activities. 12 The diphenylpropane broussonin A inhibited respiratory syncytial-virus (RSV) more effectively than the standard antiviral drug ribavirin, and its anti-aromatase activity has also been evaluated.…”

Effects of Substituents on NMR Chemical Shifts and Mass Fragmentation Patterns of 1‐Aryl‐3‐phenylpropanes

“…For example, the synthesis of the unsubstituted 1,3‐diphenylpropane ( 2d ) was done by the reduction of the chalcone 1d with NaBH 4 /Pd(OAc) 2 in CHCl 3 or with triethylsilane and trifluoroacetic acid, by the coupling of 3‐phenylpropyl halides with phenylmagnesium halides, by the high‐pressure hydrogenation of 1,3‐diphenylpropene, or by the desulfurization of benzo[ b ]thiophene derivatives . Other 1,3‐diphenylpropane derivatives reported in the literature are p ‐NO 2 ( 2k ), p ‐Br ( 2g ), m ‐Br ( 2i ), p ‐OCH 3 ( 2a ), and p ‐CH 3 ( 2b ) . The use of triethylsilane and trifluoroacetic acid in CCl 4 solution has been reported for the preparation of 2g (82% yield), 2a (82%), and 2d (80%) with the ratio of the substrate ( 1 ):HSiEt 3 :CF 3 CO 2 H = 1:3:10, and the reaction conditions of stirring at 50 °C for 6 h .…”