Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton

Rumiko Shimazawa, Hisae Takayama, Yasuyuki Fujimoto, Masato Komoda, Kosuke Dodo, Ryu Yamasaki, Ryuichi Shirai, Yukiko Koiso, Keizo Miyata, Fuminori Kato, Masanari Kato, Hiroyuki Miyachi, Yuichi Hashimoto

Research output: Contribution to journalReview articlepeer-review

36 Citations (Scopus)

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-inhihitory activity.

Original languageEnglish
Pages (from-to)259-275
Number of pages17
JournalJournal of Enzyme Inhibition
Volume14
Issue number4
DOIs
Publication statusPublished - 1999

Keywords

  • Aminopeptidase N
  • Homophthalimide
  • Inhibitor
  • Phthalimide
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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