Paracetamol (acetaminophen) esters of some non-steroidal anti-inflammatory carboxylic acids as mutual prodrugs with improved therapeutic index was written by Fadl, T. A.;Omar, F. A.. And the article was included in Inflammopharmacology in 1998.Recommanded Product: 5003-48-5 The following contents are mentioned in the article:
Paracetamol (acetaminophen) esters [4a-f] of some acidic NSAIDs were synthesized and evaluated as mutual prodrug forms with the aim of improving the therapeutic index through prevention of the gastrointestinal toxicity. The structures of the synthesized esters were confirmed by IR and 1H-NMR spectroscopy and their purity was established by elemental analyses and TLC. In-vitro stability studies revealed that the synthesized ester prodrugs 4a-f are sufficiently chem. stable in non-enzymic simulated gastric fluid (hydrochloric acid buffer of pH 1.3 (t1/2 鈭?15-45 h)) and in phosphate buffer of pH 7.4 (t1/2 鈭?4-40 h). In 80% human plasma and 10% rat liver homogenate, the mutual prodrugs were found to be susceptible to enzymic hydrolysis releasing the corresponding NSAID and paracetamol at relatively faster rates (t1/2 鈮?15-385 min and 1-140 min, resp.). Calculated log P values indicated that the prodrugs 4a-f are more lipophilic than the parent drugs. In-vivo experiments in rabbits showed higher plasma levels of ibuprofen after oral administration of its ester prodrug 4b compared with those resulting from an equivalent amount of the corresponding phys. mixture Moreover, significant improvement in latency of pain threshold in mice has been observed up to 4 h after po administration of 0.02 mmol/kg of the prodrugs, compared with the corresponding phys. mixtures Gross observations and scanning electromicrographs of the stomach showed that the prodrugs induced very little irritancy in the gastric mucosa of mice after oral administration for 4 days. These results suggest that the synthesized mutual ester prodrugs were characterized by a better therapeutic index than the parent drugs. This study involved multiple reactions and reactants, such as 4-Acetamidophenyl 2-acetoxybenzoate (cas: 5003-48-5Recommanded Product: 5003-48-5).
4-Acetamidophenyl 2-acetoxybenzoate (cas: 5003-48-5) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Recommanded Product: 5003-48-5
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics