Reaction of phthalimido alkyl acids with isopropylamine: synthesis, anti-inflammatory and antinociceptive properties

Abstract

Phthalimido alkyl acids 3-phthalimidopropionic acid (2a) and 4-phthalimidobutyric acid (2b) were treated with isopropylamine at room temperature using different solvents (dimethylformamide, dichloromethane and methanol) as the reaction medium and afforded 3-benzamido-propionic acid –2-(2- methylethyl)-carboxamide (3), 2-benzamido-2-methylethane-2-(2-methylethyl)-carboxamide (4), and 4- benzamido-butyric acid –2-(2-methylethyl)- carboxamide (5). Compound 4 was a dimmer that was least expected. Compounds 3, 4 and 5 were evaluated for antinociceptive property using acetic acid-induced writhing test. 4 exhibited the highest analgesic effect at 80 mg/kg it caused 88 % inhibition and was more pronounced than the reference drugs (indomethacin, acetylsalicylic acid and paracetamol), 3 and 5. The anti-inflammatory activity of the compounds was also screened using carrageenan- induced rat paw oedema assay and 4 showed higher activity than others except the reference drug. The effects were dose-dependent.

Key words: Phthalimido alkyl acids, mice, antinociception, mouse writhing test, isopropylamine, antiinflammatory activity.