Abstract: The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids. In the first step an intermediate α-bromo propanoicacid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatskyreaction in presence of Zn in tetrahydrofuran (THF) at –5 to 10 °C between the previouslysynthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied β-hydroxy-β-arylpropanoic acids has already been reported. These β-hydroxy-β-arylpropanoic acidsbelong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDssuch as ibuprofen. The anti-inflammatory activity and gastric tolerability of thesynthesized compounds were evaluated. Molecular docking experiments were carried outto identify potential COX-2 inhibitors among the β-hydroxy-β-aryl-alkanoic acids class.The results indicate that all compounds possess significant anti-inflammatory activity afteroral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) possess thestrongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID,and that none of tested substances or ibuprofen produced any significant gastric lesions.
Keywords: β-Hydroxy-β-arylalkanoic acids; Reformatsky reaction; anti-inflammatory activity; molecular docking simulations; COX-2 selective inhibitor
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Dilber, S.P.; Dobric, S.L.; Juranic, Z.D.; Markovic, B.D.; Vladimirov, S.M.; Juranic, I.O. Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids. Molecules 2008, 13, 603-615.
Dilber SP, Dobric SL, Juranic ZD, Markovic BD, Vladimirov SM, Juranic IO. Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids. Molecules. 2008; 13(3):603-615.
Dilber, Sanda P.; Dobric, Silva L.; Juranic, Zorica D.; Markovic, Bojan D.; Vladimirov, Sote M.; Juranic, Ivan O. 2008. "Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids." Molecules 13, no. 3: 603-615.