The novel amidocarbamate derivatives of ketoprofen.pdfVIP

MEDICINAL Med Chem Res (2011) 20:210–219 CHEMISTRY DOI 10.1007/s00044-010-9309-2 RESEARCH ORIGINAL RESEARCH The novel amidocarbamate derivatives of ketoprofen: synthesis and biological activity Zrinka Rajic′ ? Dimitra Hadjipavlou-Litina ? Eleni Pontiki ? Jan Balzarini ? Branka Zorc Received: 16 July 2009 / Accepted: 13 January 2010 / Published online: 3 February 2010 ó Springer Science+Business Media, LLC 2010 Abstract A series of novel ketoprofen derivatives 4a– Keywords Ketoprofen amide á Carbamate á Antioxidant á j bearing both amide and carbamate functionalities were Peroxidation á Lipoxygenase á Antiviral activity á prepared using the benzotriazole method of carboxylic and Cytostatic activity hydroxy group activation. Selective reduction of ketopro- fen produced hydroxy derivative 2, which in the reaction with one or two moles of 1-benzotriazole carboxylic acid Introduction chloride (1) gave benzotriazole derivatives 3a and 3b, respectively. Compounds 3a and 3b with various amines Ketoprofen (Ket) is a non-steroidal anti-in?ammatory drug afforded amidocarbamates 4a–j. Antioxidative screenings (NSAID) with pronounced analgesic and antipyretic revealed that the prepared compounds 3b and 4a–j possess properties. Numerous ketoprofen derivatives have been excellent lipid peroxidation inhibition at 0.1 mM concen- synthesized in order to minimize side-effects, prolong tration, higher than 95% for the derivatives bearing aro- plasma half-life and increase solubility (Bonina et al., matic, cycloalkyl or heterocyclic substituents. Two of the 2002a, b, 2003). Some amides have proved to be useful compounds, 3b and 4g, also show high soybean lipoxy- prodrugs, while the others possess anti-in?ammatory genase inhibition activity (95 and 83.5%, respectively). On activity independent of the parent compound. It has been the other hand, the amidocarb