N -Acylated and N -Alkylated 2-Aminobenzothiazoles Are Novel Agents That Suppress the Generation of Prostaglandin E 2 .

The quest for novel agents to regulate the generation of prostaglandin E 2 (PGE 2 ) is of high importance because this eicosanoid is a key player in inflammatory diseases. We synthesized a series of N -acylated and N -alkylated 2-aminobenzothiazoles and related heterocycles (benzoxazoles and benzimidazoles) and evaluated their ability to suppress the cytokine-stimulated generation of PGE 2 in rat mesangial cells. 2-Aminobenzothiazoles, either acylated by the 3-(naphthalen-2-yl)propanoyl moiety (GK510) or N -alkylated by a chain carrying a naphthalene (GK543) or a phenyl moiety (GK562) at a distance of three carbon atoms, stand out in inhibiting PGE 2 generation, with EC 50 values ranging from 118 nM to 177 nM. Both GK510 and GK543 exhibit in vivo anti-inflammatory activity greater than that of indomethacin. Thus, N -acylated or N -alkylated 2-aminobenzothiazoles are novel leads for the regulation of PGE 2 formation.