European Journal of Medicinal Chemistry 2009-01-01

Design and synthesis of newN-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides as anti-inflammatory agents

Chiao-Ting Yen, Tsong-Long Hwang, Yang-Chang Wu, Pei-Wen Hsieh

Index: Eur. J. Med. Chem. 44 , 1933-40, (2009)

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Abstract

Twenty-four new dipeptide analogs ( 1– 24) of aurantiamide acetate were designed, synthesized, and assayed for effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, seven N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides ( 6, 9, 12, 14, 17, 18 and 20) showed potent inhibitory effects. Compounds 9 and 18 showed the most selective effects against human neutrophil elastase release, with IC 50 values of 0.8 ± 0.1 and 1.7 ± 0.6 μM, respectively, and were 130-fold more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in this anti-inflammatory assay. These two compounds could be developed as new lead anti-inflammatory agents.