Synthesis and Anti-inflammatory Activity of Some Novel Trisubstituted Thiophene Analogues

Abstract

Trisubstituted thiophenes analogues (IVa-IVf) were designed, synthesized, characterized and evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at 10 mg/kg dose. In search for better anti-inflammatory agents having optimum requirements at positions 3 and 5 of thiophenes with a conformationally restricted morpholine at position 2, some 2-morpholino thiophene derivatives with
phenyl, 4-methylphenyl (4-CH3, σ = -0.17; π = +0.56) at position 3 and Ar = 4-methoxyphenyl (4-OCH3, σ = -0.27; π = -0.04), 4-nitrophenyl (4-NO2, σ = +0.78; π = -0.28) at position 5 of the thiophene ring (IVa-IVd) were synthesized. Similarly keeping phenyl, 4-methylphenyl at position 3 and Ar = coumarin-3-yl at position 5 of thiophene, IVe and IVf were synthesized. The most active compound of the series was IVb, which showed 55% protection of inflammation at a dose of 10 mg/kg. All the targeted trisubstituted thiophenes
(IVa-IVf) were found to have poor anti-inflammatory activity as compared to the standard drug diclofenac sodium, which showed protection of 79% at 10 mg/kg dose.

Keywords: trisubstituted thiophenes, morpholine, coumarin, anti-inflammatory activity, diclofenac sodium

Ethiopian Pharmaceutical Journal Vol. 24 (2) 2006: pp. 84-90