Synthesis and comparative anti-phlogistic potency of new proteinogenic amino acid conjugates of 2-[2,6-dichlorophenyl-1-amino]phenyl acetic acid "diclofenac"

Acta Pol Pharm. 1998 May-Jun;55(3):211-21.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Diclofenac / analogs & derivatives
  • Diclofenac / chemical synthesis*
  • Diclofenac / pharmacology*
  • Male
  • Rats
  • Stomach Ulcer / chemically induced
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diclofenac