Etodolac ester

QH12N2 19275-55-9) see Etodolac ethylphenylmalondiamide (C11H14N2O2 7206-76-0) see Primidone ethylphenylmalonic acid diethyl ester see under diethyl cthylphenylmalonate... 

As shown in the following scheme, one synthetic route to etodolac involves acid catalyzed (p-TSA or P2O5) condensation of an indole starting material, tryptophol, with a keto ester, such as, ethyl propionylacetate. 

The mass spectrum of etodolac methyl ester was obtained using a Hewlett-Packard quadrupole mass spectrometer, operating in the GC-MS positive electron impact (EI+) mode [15,16]. The monitored ions were at m/z 154, 168,198, 213, 228, 272, and 301, and assignments for these are summarized in Table 6. 

A TLC method has been developed to determine etodolac and its metabolites (6-OH-etodolac and 7-OH-etodolac) in biological fluids and extracts (before and after enzyme hydrolysis) [15]. The method used silica gel plates and hexane-ethyl acetate-acetic acid (60 40 2, v/v) and hexane-ethyl acetate (70 30, v/v) solvent systems to separate the free carboxylic acid and methyl esters of etodolac and the two metabolites. The relative retention (Rf) values obtained under these conditions were 0.29,0.20 and 0.24 for etodolac, 6-OH-etodolac, and 7-OH-etodolac respectively. An Rf value of 0.45 was obtained for methyl ester of etodolac. 

A reverse-phase microbore HPLC method with photodiode-array detection and UV spectral library was developed for toxicological screening of various drugs in plasma including etodolac and its methyl ester [30]. Sample preparation involved addition of prazepam (internal standard) to 500 pL of plasma followed by addition of 30 pL of 1M sodium hydroxide and 5 mL of dichloromethane. After shaking the sample for 1 minute and centrifuging, the upper aqueous layer was discarded. The organic phase was evaporated and reconstituted with 50 pL methanol and 20 pL water ... 

Etodolac and etodolac methyl ester were found to have retention times of 7.4 and 14.2 minutes, respectively. However, no information on the quantitation of the drug was presented. 

In a study NSAIDs indomethacin (2-[l-(4-chlorobenzoyl)-5-methoxy-2-methyl-indol-3-yl]acetic acid), acemetacin (l-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid carboxymethyl ester), and etodolac (( )-l,8-diethyl-l,3,4,9-tetrahydropyrano-(3,4-b)indole-l-acetic acid) were tested on different ROS generating systems (Fig. 1). There are some satisfactory results that confirm that the anti-inflammatory activity of these compounds may be also partly due to their ability to scavenge ROS and RNS. The observed effective scavenging activity may contribute to the anti-inflammatory therapeutical effects [92,100]. 

Sample preparation Hydrolyze 1 mL urine in 200 mM pH 4.6 sodium acetate buffer with 40000 U Glusulase (DuPont) at 37° for 20 h, extract with 20 g neutral Amberlite XAD-2 resin. Elute the resin with 40 mL MeOH and methylate with excess (trimethylsi-lyDdiazomethane to give N-methyl etodolac methyl ester. 

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