Mefenamic acid

Ullman condensation of m-trifluoromethylaniline (13) with o-iodobenzoic acid in the presence of copper-bronze affords flu-fenamic acid (14). An analogous reaction of o-chlorobenzolc acid with 2,3-dimethylaniline (15) gives mefenamic acid (16) meclofenamic acid (18) is obtained by Ullman condensation employing 2,6-dlchloro-3-methylaniline (17). 

K. Yamashita, M. Motohashi and T. Yashiki, Column-switching techniques for high-performance liquid cliromatography of ibuprofen and mefenamic acid in human serum with shoit-wavelength ultraviolet detection , J. Chromatogr. 570 329-338 (1991). 

NSAIDs are of diverse chemical structures salicylates (aspirin, sulphasalazine), indole acetic acids (indomethacin, etodolac), heteroaryl acetic acids (diclofenac), arylpropionic acids (ibuprofen, naproxen), anthranilic acids (mefenamic acid) and enolic acids (piroxicam, meloxicam). 

Tables 3 and 4 list thermodynamic values calculated for polymorphs of chloramphenicol palmitate and mefenamic acid, respectively. Absorption studies of chloramphenicol palmitate in humans show that suspensions containing polymorph B of chloramphenicol palmitate gave blood levels approximately 10 times higher than those produced by suspensions of polymorph A [49], This may be due to the significant (-774 cal/mol) free energy difference between the polymorphs resulting in a substantial difference in their solubility and dissolution behavior. This theory is supported by the almost identical blood levels due to polymorphs I and n of mefenamic acid, which have a small free energy difference (-231 cal/mol) and similar solubility and dissolution behavior (Table 4).

Table 4 Thermodynamic Values for Polymorphs of Mefenamic Acid...

A Aguiar, JE Zelmer. Dissolution behavior of polymorphs of chloramphenicol pal-mitate and mefenamic acid. J Pharm Sci 58(8) 983-987, 1969. 

Mefenamic is a nonsteroidal anti-inflammatory drug used to treat pain, including menstrual pain. Hata et al. [11] treated that drug with P. sordida, and obtained a 90% reduction in mefenamic acid concentration (initial concentration 24 mg L ) after 6 days. The system produced four metabolites, identified as 3 -hydroxymethyl-mefenamic acid, 3 -hydroxymethyl-5-hydroxymefenamic acid, 3 -hydroxmethyl-6 -hydroxymefenamic acid, and 3 -carboxymefenamic acid. Moreover, the authors confirmed that the fungus almost completely removed the acute lethal toxicity of mefenamic towards the freshwater crustacean Thamnocephalus platyurus after 6 days of treatment, suggesting that the metabolites are less toxic than the parental compound. 

A number of compounds activate TRPA1 without any apparent ability to form covalent adducts, including nonelectrophilic fenamate nonsteroidal anti-inflammatory drugs (NSAIDs), such as flufenamic acid (17, FFA), niflumic acid (18, NFA), and mefenamic acid (19, MFA) [13]. Phenols such as thymol (20) and 2-ferf-butyl-5-methylphenol (21) have been shown to activate human TRPA1 with micromolar EC50 values in stably transfected HEK293 cells [14]. 

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