SYNTHESIS OF NOVEL (R)-5-BROMO-3-(NMETHYLPYRROLIDINE-2-YL-METHYL)-1H (SUBSTITUTED)- INDOLE DERIVATIVES AS POTENTIAL COX-2 INHIBITORS VIA JAPP-KLINGEMANN AND FISCHER INDOLE CYCLIZATION REACTIONS

A series of novel (R)-5-bromo-3-(N-methylpyrrolidine-2-yl-methyl)-1H (substituted)-indole (T1-T5) derivates were synthesized by electrophilic substitution at 1st position of (R)-5-bromo-3-(N-methylpyrrolidine-2-yl-methyl)-1Hindole with various halides. The starting material (R)-5-bromo-3-(N-methylpyrrolidine-2-yl-methyl)-1H-indole was synthesized from 4-bromo aniline by multistep synthesis. The synthesized compounds were characterized by IR, 1H NMR and MASS spectroscopy and newly synthesized compounds were evaluated for their analgesic activity by tail immersion technique using wistar albino mice. Among the synthesized compounds T3, T4, T5.have shown significant activity by tail immersion technique. Compound (R)- 5-bromo-1-ethyl-3-[(1-methylpyrrolidin-2-yl)methyl]-1Hindole (T3) emerged as the most potent analgesic agent and it is equipotent when compared to the reference standard diclofenac sodium. Keywords: Indole derivatives; Analgesic activity; Tail immersion technique