Synthesis and Analgesic and Anti‐inflammatory Activity of Some New (6‐Acyl‐2‐benzoxazolinone and 6‐Acyl‐2‐benzothiazolinone Derivatives with Acetic Acid and Propanoic Acid Residues

Abstract

In this study for developing potent analgesic and anti-inflammatory compounds, we synthesized 6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid side chain, and performed preliminary screening of their in vivo analgesic and anti-inflammatory activities at a single dose of 100 mg/kg inmice by a p-benzoquinone-induced writhing test and a Carrageenaninduced hind paw edema model, respectively. We also determined their gastric ulceration effects in the tested animals. Propanoic acid derivatives were generally found to have higher analgesic and anti-inflammatory activities, and among them, 3-(6-benzoyl-2-benzothiazolinon-3-yl)propanoic acid (Compound 4 a) exhibited the highest analgesic and anti-inflammatory activity. However, all compounds showed lower anti-inflammatory effects than we observed for indomethacin at 10 mg/kg dose. Consequently, 6-acyl-2-benzoxazolinone/2-benzothiazolinones having propanoic acid side chain might lead to further studies for developing better candidates with potent analgesic and anti-inflammatory effects while acetic acid derivatives do not exhibit comparable satisfactory features.

Crystal structure of 3-{5-[(2-chlorophenyl)carbonyl]-2-oxo-1,3- benzothiazol-3(2H)-yl}propanoic acid, C17H12ClNO4S

“…All propanoic acid derivatives might lead to further studies developing compound with better analgesic and anti-inflammatory activity. The propanoic acid residue caused an overall increase in the analgesic and anti-inflammatory activity [1]. In the molecule of the title compound (figure, top), the bonding parameters are comparable with those observed previously for the similar compounds [2][3][4].…”

Crystal structure of methyl (6-(2-fluorobenzoyl)-5-chloro- 2-benzoxazolinon-3-yl)-acetate, C17H11ClFNO5

“…Benzothiazolinone/2-benzoxazolinone derivatives exhibit avariety of pharmacologicale ffects, including analgesic and antiinflammatory activity [1]. Inthe title compound the F1-C2distance 1.350(2)Åis in agreement with thatf or ethyl[6-(2-fluorobenzoyl)-2-oxo-benzothiazolin-3-yl]-butanoate [2] (1.346(3) Å).…”

Amide derivatives of [6-acyl-2-benzothiazolinon-3-yl] acetic acids as potential analgesic and anti-inflammatory compounds

“…In the synthesis of resulting amide derivatives, 2-benzothiazolinone, 6-acyl-2-benzothiazolinones (1a-s) and (6-acyl-2-benzothiazolinon-3-yl)acetic acids (3a-s) were prepared according to the previously published procedures (Fife et al, 1975 Unlü et al, 2003a). Compounds 3a-s were then treated with oxalyl chloride to prepare the corresponding acid chlorides, which were then reacted without subsequent purification with appropriate amine derivatives to obtain resulting novel amide derivatives (4a-s).…”

“…2-Oxo-benzothiazoline, 6-acyl-2-benzothiazolinone (1), and [6-(2-chloro/fluorobenzoyl)-2-benzothiazolinon-3-yl]acetic acids (3) were prepared according to the previously published procedures (Unlü et al, 2003a;Cakır et al, 1997;Dalaeva et al, 1994;Petrov et al, 1994). Infrared (IR) spectra were recorded on a Bruker Vector 22 IR (Opus Spectroscopic Software Version 2.0) spectrometer (KBr, r, cm -1 ).…”