Synthesis and comparative anti-phlogistic potency of new proteinogenic amino acid conjugates of 2-[2,6-dichlorophenyl-1-amino]phenyl acetic acid "diclofenac".
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
A M
AM
Department of Chemistry of Tanning Materials and Proteins, National Research Centre, Dokki, Cairo, Egypt.
Abo-Ghalia
A M
AM
el-Araky
W I
WI
Awad
H M
HM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D004008:Diclofenac / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac