jm0608199_si_001.pdf (24.58 kB)

Synthesis of 2-Methyl-3-indolylacetic Derivatives as Anti-Inflammatory Agents That Inhibit Preferentially Cyclooxygenase 1 without Gastric Damage

Download (24.58 kB)
journal contribution
posted on 28.12.2006, 00:00 by Elisa Perissutti, Ferdinando Fiorino, Christian Renner, Beatrice Severino, Fiorentina Roviezzo, Lidia Sautebin, Antonietta Rossi, Giuseppe Cirino, Vincenzo Santagada, Giuseppe Caliendo
Novel substituted 2-methyl-3-indolylacetic derivatives were synthesized and evaluated for their activity in vitro and in vivo on COX-1 and COX-2. Active compounds were screened to determine their gastrointestinal tolerability in vivo in the rat. Results showed that 3 and 4 preferentially inhibited COX-1 in vitro and in vivo. MD simulations indicated an induced fit for COX-1 but not for COX-2, probably because of a lower plasticity of the latter.