Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents

Determination of protein binding for novel 2‐(2‐hydroxypropanamido)‐5‐trifluoromethyl benzoic acid enantiomers to rats, dogs, and humans plasma by UPLC‐MS/MS

“…Moreover, the bound fraction of R ‐HFBA in rat plasma at 150 μg/mL was significantly higher than that of S ‐HFBA, which provided a novel explanation for some pharmacokinetic differences of HFBA enantiomers in rats. In our previous study, R ‐HFBA had greater t 1/2 , AUC and lower clearance than its antipode . Therefore, the discrepancy of the plasma protein‐binding capacity between R ‐HFBA and S ‐HFBA could be a reason leading to the different pharmacokinetic parameters in rats.…”

“…HFBA could be an effective and safe agent for anti‐inflammatory and antiplatelet aggregation therapy with prolonged pharmacological activity. In our previous study, the different pharmacokinetic profiles of the two enantiomers in rats were observed after administration of R ‐HFBA and S ‐HFBA . R ‐HFBA exhibited greater t 1/2 , AUC, and lower clearance than those of S ‐HFBA.…”

“…2‐(2‐hydroxypropanamido)‐5‐trifluoromethyl benzoic acid (HFBA; Figure ), with one chiral center and two enantiomers, R ‐/ S ‐HFBA, was initially synthesized by our group. R ‐/ S ‐HFBA presented remarkable anti‐inflammatory and antiplatelet aggregation activities superior to aspirin, but no gastrointestinal toxicity . The mechanism of effect of HFBA was found to inhibit COX‐1/COX‐2 enzyme leading to a reduction of inflammatory mediators and thromboxane A 2 .…”

Exploring stereoselective excretion and metabolism studies of novel 2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid enantiomers

“…R-/S-HFBA presented remarkable anti-inammatory and antiplatelet aggregation activities superior to aspirin, with less gastrointestinal toxicity. 10 The action mechanism of HFBA was found to inhibit COX enzyme resulting in a reduction of thromboxane A 2 and inammatory mediators. HFBA could be a effective and safe agent for anti-inammatory and antiplatelet aggregation therapy with prolonged pharmacological activity.…”

“…R-HFBA exhibited greater t 1/2 , AUC and lower clearance (CL) than those of S-HFBA. 10 Metabolite identication and excretion studies play a crucial role in the discovery and development of new drugs. 11 Metabolism is the biochemical process to detoxify and eliminate xenobiotics and endogenous compounds through converting them into more hydrophilic species.…”