17243-26-4

Upstream product

• 103-90-2 4-acetaminophenol 
• 541-41-3 chloroformic acid ethyl ester 
• 35179-98-7 chloromethyl ethyl carbonate 
• 82619-14-5 ethoxycarbonyloxymethyl iodide 
• 108-95-2 phenol 

Relevant academic research and scientific papers

Overcoming steric effects in the coupling reaction of alkyloxycarbonyloxymethyl (AOCOM) halides with phenols: an efficient synthesis of AOCOM phenolic prodrugs

Steric hindrance is a key factor in the coupling reaction of AOCOM halides with phenols. Sterically unhindered alkoxy groups favor the formation of acylated phenol. Under phase-transfer conditions, alkylated phenol is favored regardless of steric hindrance.

Topical delivery of a model phenolic drug: Alkyloxycarbonyl prodrugs of acetaminophen

Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown. Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (JMIPM), solubilities in IPM (SIPM) and water (SAQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K IPM:4.0) were measured for two series of AOC derivatives of acetaminophen (APAP); their solubilities in pH 4.0 buffer (S4.0) were estimated from SIPM/KIPM: 4.0. Log JMIPM values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Δ log J′IPM) was calculated. The J MIPM, SIPM, S4.0, and molecular weight (MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log JMIPM = x + y log SIPM (1 - y) log S4.0 - z MW. Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log JMIPM (Δ log J′MIPM = 0.275 ± 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: 2 = -0.322, 0.530, 0.00337 and 0.92, respectively. Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on SIPM, S 4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.

Specificity of esterases and structure of prodrug esters: Reactivity of various acylated acetaminophen compounds and acetylaminobenzoated compounds

The relative rates of enzymatically catalyzed hydrolysis of various esters of p-acetylaminobenzoic acid (APAB) and variously acylated acetaminophen (APAP) derivatives were measured. Neutral, anionic, and cationic esters were examined. The enzyme sources adopted were rat intestinal homogenate, rat liver homogenate, rat plasma, and a partly purified commercial enzyme. In both APAB and APAP esters, neutral esters were the most sensitive of the enzyme sources examined, and the sensitivity was due to the carbon chain length. The APAP esters were enzymatically more stable than the APAP esters. The relative rates of hydrolysis of these esters varied depending on the enzyme source. The ability of structure recognition was good in rat intestinal homogenate, but weak in rat plasma. These results suggest that ester prodrugs can be designed to cleave preferentially at selected sites along the pathway between absorption and disposition in the body.