Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Structure-based design, chemistry and activity evaluation. II.
A novel class of potent aminopeptidase N inhibitors with 3-amino-cyclic-imide scaffold is described. The preliminary biological test revealed that all the compounds displayed high specific inhibitory activity against aminopeptidase N compared with previous work because of the existence of free amino group. Compounds containing hydroxamate group are more potent than carboxyl and ester derivatives. Compound 13f potentially inhibited APN activity with IC(50) value of 1.8 microM and displayed specific activity profiles in cells assay and in vivo anti-metastasis assay.
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Jinan, Shandong, PR China.
Qianbin
Q
Li
Hao
H
Fang
Xuejian
X
Wang
Wenfang
W
Xu
D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D007094:Imides / Q000737:chemistry; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D007094:Imides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D018826:CD13 Antigens