Amide and ester derivatives of N-3-(4-methoxyumaroyl)-(S)-2,3-diaminopropanoic acid: The selective inhibitor of glucosamine-6-phosphate synthase

Several amide and ester derivatives of a glutamine analogue, N-3-(3-melhoxy fumaroyl)-(S)-2.3-diaminopropanoic acid (FMDP) (1-8), were synthesized and evaluated for the inhibitory activity in regard to wglucdsaminr-6-phosphate synthase from Candida albicans. The syntheses were accomplished by the rea ction of N-2-tert-butoxycarbonyl-N-3-(4-methoxyfumaroyl)-(S)-2,3-diarninopr opanoic acid (BocFMDP) with the corresponding amines to give the FMDP amide s (1-4) or with alkyl halides to give corresponding esters of FMDP (5-8). A mong the synthesized compounds, the acetoxymethyl eater of FMDP was the mos t active inhibitor of the enzyme. Its IC50 value compared to that of FMDP ( 4 muM) was equal to 11.5 muM. The methyl and allyl esters and the N-hexyl-N -methyl amide of FMDP exhibited a moderate enzyme inhibitory activity. (C) 2001 Elsevier Science Ltd. All rights reserved.