Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors.
Herein we report a series of novel chloramphenicol amine derivatives as aminopeptidase N (APN)/CD13 inhibitors. All compounds were synthesized starting from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol. The preliminary biological screening showed that some compounds exhibited potent inhibitory activity against APN. It should be noted that one compound, 13b (IC(50)=7.1 microM), possess similar APN inhibitory activity compared with Bestatin (IC(50)=3.0 microM).
Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44 West Culture Road, Ji'nan, Shandong 250012, China.
Kanghui
K
Yang
Qiang
Q
Wang
Li
L
Su
Hao
H
Fang
Xuejian
X
Wang
Jianzhi
J
Gong
Binghe
B
Wang
Wenfang
W
Xu
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D020134:Catalytic Domain; D002701:Chloramphenicol / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000494:pharmacology
D000588:Amines; D011480:Protease Inhibitors; D002701:Chloramphenicol; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex