- Synthesis and comparative anti-phlogistic potency of new proteinogenic amino acid conjugates of 2-[2,6-dichlorophenyl-1-amino]phenyl acetic acid 'Diclofenac'
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New proteinogenic amino acids conjugates of 2-[2,6-dichlorophenyl-1-amino]phenyl acetic acid 'Diclofenac', [I] were synthesized. Glycine methyl ester and L-methionine ethyl ester were coupled with [I] via the active ester method to give the corresponding 2-[2,6-dichlorophenyl-1-amino]benzyl carboxy N-amino acid ester of the type [IIa, b], respectively, which were hydrolyzed in alkaline medium to yield the free amino acids [IIIa, b]. Condensation of IIIa with glycine methyl ester using a modified classical carbodiimide (DCCI) method gave the corresponding 'Diclofenac' glycylglycine methyl ester [IVa]. Hydrolysis of compounds IVa gives the corresponding acid Va. Thionation of compounds IIb and IVa by reaction with Lewesson's Reagent (LR), afforded the corresponding thio-analogues (VIa and IVb). Interestingly, while retaining considerable comparative anti-phlogistic activity (anti-inflammatory and analgesic), the synthesized candidates proved to be practically nonulcerogenic in rats.
- Shalaby, Ahmed M.,Abo-Ghalia,El-Araky,Awad
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p. 211 - 221
(2007/10/03)
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