Ring opening of 1-phthaloylimido-[4-(2-methoxyphenyl) piperazin-1-yl]alkyl derivatives: synthesis, analgesic and anti-inflammatory properties of products.

Phthaloylimidoalkyl derivatives (1a, 1b) were treated with isopropylamine to give 3-benzamido-1-(4-(2-methoxyphenyl)piperazin-1-yl)]propyl-2-isopropyl carboxamide (3a) and 4-benzamido-1-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-2-isopropyl carboxamide (3b). The compounds were unequivocally characterized by IR, NMR and MS spectra and elemental analysis. Carrageenan-induced rat paw assay was used to screen 3a and 3b for anti-inflammatory activity. 3b significantly (p <0.001) inhibited the inflammation caused by carrageenan after 3 h compared to 3a and indomethacin. Mouse writhing assay was performed to evaluate 3a and 3b. It revealed that 3b (10 mg/kg) produced 71% inhibition when compared to 3a (40 mg/kg) and acetylsalicylic acid (100 mg/kg). The results show that the length of the alkyl chain that separates the terminal nitrogen atom from the phthalic acid moiety also affects the activity of 3a and 3b in a dose dependent manner.