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

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