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 journalArticle

35 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
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Imides
CD13 Antigens
Skeleton
Molecules
Peptide Hydrolases
Structure-Activity Relationship
Tumors
N-phenylphthalimide
Phenylhomophthalimide
Neoplasms
N-(2,6-diethylphenyl)homophthalimide

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Biochemistry
  • Drug Discovery
  • Pharmacology

Cite this

Shimazawa, R., Takayama, H., Fujimoto, Y., Komoda, M., Dodo, K., Yamasaki, R., ... Hashimoto, Y. (1999). Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton. Journal of Enzyme Inhibition, 14(4), 259-275.

Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton. / Shimazawa, Rumiko; Takayama, Hisae; Fujimoto, Yasuyuki; Komoda, Masato; Dodo, Kosuke; Yamasaki, Ryu; Shirai, Ryuichi; Koiso, Yukiko; Miyata, Keizo; Kato, Fuminori; Kato, Masanari; Miyachi, Hiroyuki; Hashimoto, Yuichi.

In: Journal of Enzyme Inhibition, Vol. 14, No. 4, 1999, p. 259-275.

Research output: Contribution to journalArticle

Shimazawa, R, Takayama, H, Fujimoto, Y, Komoda, M, Dodo, K, Yamasaki, R, Shirai, R, Koiso, Y, Miyata, K, Kato, F, Kato, M, Miyachi, H & Hashimoto, Y 1999, 'Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton', Journal of Enzyme Inhibition, vol. 14, no. 4, pp. 259-275.
Shimazawa R, Takayama H, Fujimoto Y, Komoda M, Dodo K, Yamasaki R et al. Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton. Journal of Enzyme Inhibition. 1999;14(4):259-275.
Shimazawa, Rumiko ; Takayama, Hisae ; Fujimoto, Yasuyuki ; Komoda, Masato ; Dodo, Kosuke ; Yamasaki, Ryu ; Shirai, Ryuichi ; Koiso, Yukiko ; Miyata, Keizo ; Kato, Fuminori ; Kato, Masanari ; Miyachi, Hiroyuki ; Hashimoto, Yuichi. / Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton. In: Journal of Enzyme Inhibition. 1999 ; Vol. 14, No. 4. pp. 259-275.
@article{23a2cce95b8c4053a396fce350f996e1,
title = "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-inhihitory activity.",
keywords = "Aminopeptidase N, Homophthalimide, Inhibitor, Phthalimide, Structure-activity relationship",
author = "Rumiko Shimazawa and Hisae Takayama and Yasuyuki Fujimoto and Masato Komoda and Kosuke Dodo and Ryu Yamasaki and Ryuichi Shirai and Yukiko Koiso and Keizo Miyata and Fuminori Kato and Masanari Kato and Hiroyuki Miyachi and Yuichi Hashimoto",
year = "1999",
language = "English",
volume = "14",
pages = "259--275",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
issn = "1475-6366",
publisher = "Informa Healthcare",
number = "4",

}

TY - JOUR

T1 - Novel small molecule nonpeptide aminopeptidase N inhibitors with a cyclic imide skeleton

AU - Shimazawa, Rumiko

AU - Takayama, Hisae

AU - Fujimoto, Yasuyuki

AU - Komoda, Masato

AU - Dodo, Kosuke

AU - Yamasaki, Ryu

AU - Shirai, Ryuichi

AU - Koiso, Yukiko

AU - Miyata, Keizo

AU - Kato, Fuminori

AU - Kato, Masanari

AU - Miyachi, Hiroyuki

AU - Hashimoto, Yuichi

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Aminopeptidase N

KW - Homophthalimide

KW - Inhibitor

KW - Phthalimide

KW - Structure-activity relationship

UR - http://www.scopus.com/inward/record.url?scp=6544274842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6544274842&partnerID=8YFLogxK

M3 - Article

C2 - 10445048

AN - SCOPUS:6544274842

VL - 14

SP - 259

EP - 275

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 4

ER -