Novel small molecule nonpeptide aminopeptidase n inhibitors with a cyclic imide skeleton.

Abstract

A novel series of small molecule nonpeptide aminopeptidase N (APN) inhibitors with a N-phenylphthalimide or N-phenylhomophthalimide skeleton were prepared. Evaluation of their protease inhibitory activities revealed that (i) some N-phenylphthalimide analogs are potent APN inhibitors, but they are also inhibitors of another protease, dipeptidylpeptidase IV (DPP-IV), and (ii) some N-phenylhomophthalimide analogs, including 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22), are potent and specific inhibitors of APN without DPP-IV-inhibitory activity. The structure-activity relationship studies of N-phenylphthalimides and N-phenylhomophthalimides are reviewed. PIQ-22 showed potent tumor-cell invasion-inhibitory activity.

• Authors: R Shimazawa, H Takayama, Y Fujimoto, M Komoda, K Dodo, R Yamasaki, R Shirai, Y Koiso, K Miyata, F Kato, M Kato, H Miyachi, Y Hashimoto
• Journal: Journal of enzyme inhibition (J Enzyme Inhib) Vol. 14 Issue 4 Pg. 259-75 ( 1999) ISSN: 8755-5093 [Print] Switzerland
• PMID: 10445048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Phthalimides
• Protease Inhibitors
• CD13 Antigens
• Leucine
• ubenimex

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• CD13 Antigens (antagonists & inhibitors)
• Leucine (analogs & derivatives, pharmacology)
• Neoplasm Invasiveness
• Phthalimides (chemistry, pharmacology)
• Protease Inhibitors (chemistry, pharmacology)
• Structure-Activity Relationship