| Acceptance rate | 46% |
|---|---|
| Time to first decision | 20 days* |
| Time to decision with review | 50 days* |
*Approximate number of days
**The days mentioned above are averages and do not indicate exact durations. The process may vary for each article.
ACTA Pharmaceutica Sciencia
2016 , Vol 54 , Num 1
Design and Synthesis of Stable N-[2-(aryl/heteroaryl substituted)ethyl] propanamide Derivatives of (S)-Ketoprofen and (S)-Ibuprofen as Non-Ulcerogenic Anti-Inflammatory and Analgesic Agents
1 İstanbul Medipol University, School of Pharmacy, 34810, İstanbul, Turkey.2 Gazi University, Faculty of Pharmacy, 06330, Ankara, Turkey.
3 Yeditepe University, Faculty of Pharmacy, 34755, Istanbul, Turkey.
DOI : 10.23893/1307-2080.APS.0546 The carboxylic acid groups of (S) ketoprofen and (S) ibuprofen were brought into reaction with substituted ethylamine derivatives to form (S)-2-(4- isobutylphenyl)- and (S)-2-(3-benzoylphenyl)-N-[2-(aryl/heteroaryl substituted) ethyl]propanamide derivatives. Then, these sets were evaluated in terms of their in vivo anti-inflammatory and analgesic properties using the carrageenan-induced paw edema and p-benzoquinone-induced writhing models. Among the synthesized compounds, (S)-2-(4-isobutylphenyl)-N-[2-(pyrrolidin-1-yl)ethyl]propanamide (4f) showed the highest activity at the 100mg/kg dose inducing no gastric lesions when compared to the parent compound, ibuprofen. In vitro studies on chemical stability revealed that the amide derivative with the highest activity (4f) was chemically stable in simulated gastric (pH 1.2) and intestinal fluids (pH 7.4). In 80% v/v human plasma, the amide derivative was found to be stable against plasma hydrolases over the experimental period. The most active compound, (S)- 2-(4-isobutylphenyl)-N-[2-(pyrrolidin-1-yl)ethyl]propanamide, was also studied in 10% rat liver homogenate (pH 7.4) to identify its release pattern as a prodrug. Keywords : Ketoprofen, Ibuprofen, anti-inflammatory, NSAIDs