Background: Designing new anti-inflammatory agents possessing safe therapeutic
profiles and devoid of potential undesirable side effects is an active field in medicinal chemistry.
Thus, a series of N-(4-substituted phenyl)glycine derivatives was designed and synthesized.
The idea behind the design is to utilize the bifunctionality of 4-aminoacetophenone via
converting the amino group into glycine derivative as a side arm to mimic the glycine amino
acid enhancing the overall physicochemical and biological characteristics. In addition, the
opposite acetyl group was used as a center for modification and derivatization.
Methods: The starting N-(4-acetylphenyl)glycine was converted into two intermediates: the
chalcone analog 2 and the thiosemicarbazone derivative 8. Both 2 and 8 were derivatized
and/or cyclized into different heterocyclic target derivatives (3-7 and 9-12). The target compounds
were screened for anti-inflammatory activity using carrageenan-induced rat paw
Results: The results showed that compounds 6, 7, and 3, were the most active among the
tested compounds at 50 mg/kg dose level with % inhibition of edema of 51.82, 43.80, and
Conclusion: The authors succeeded to introduce a simple and versatile skeleton with a side
arm resembling the glycine amino acid; imparting a potential improvement in physicochemical
properties. We utilize the other side of the skeleton’s aromatic ring as a center for derivatization.
The chalcone analog and its cyclized heterocyclic derivatives were of remarkably
higher anti-inflammatory activity than the thiosemicarbazone and its derivatives.