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
N1 - Funding Information:
The work presented in this review was supported in part by Grants-in-Aid for Scientific Research from The Ministry of Education, Science, Sports and Culture, Japan, and by funds for the Promotion of Fundamental Studies in Health Science from the Organization for Pharmaceutical Safety and Research (OPSR).
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
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U2 - 10.3109/14756369909030321
DO - 10.3109/14756369909030321
M3 - Review article
C2 - 10445048
AN - SCOPUS:6544274842
SN - 1475-6366
VL - 14
SP - 259
EP - 275
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 4
ER -