Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors

Kanghui Yang; Qiang Wang; Li Su; Hao Fang; Xuejian Wang; Jianzhi Gong; Binghe Wang; Wenfang Xu

doi:10.1016/j.bmc.2009.04.038

Design and synthesis of novel chloramphenicol amine derivatives as potent aminopeptidase N (APN/CD13) inhibitors

Bioorg Med Chem. 2009 Jun 1;17(11):3810-7. doi: 10.1016/j.bmc.2009.04.038. Epub 2009 Apr 24.

Authors

Kanghui Yang¹, Qiang Wang, Li Su, Hao Fang, Xuejian Wang, Jianzhi Gong, Binghe Wang, Wenfang Xu

Affiliation

¹ Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44 West Culture Road, Ji'nan, Shandong 250012, China.

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemical synthesis*
Amines / pharmacology*
CD13 Antigens / antagonists & inhibitors*
Catalytic Domain
Chloramphenicol / chemical synthesis
Chloramphenicol / pharmacology
Drug Design*
Enzyme Activation / drug effects*
HL-60 Cells
Humans
Inhibitory Concentration 50
Leucine / analogs & derivatives
Leucine / pharmacology
Models, Biological
Molecular Structure
Protease Inhibitors / pharmacology

Substances

Amines
Protease Inhibitors
Chloramphenicol
CD13 Antigens
Leucine
ubenimex