Novel small molecule nonpeptide aminopeptidase n inhibitors with a cyclic imide skeleton.
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.
Shimazawa
R
R
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Takayama
H
H
Fujimoto
Y
Y
Komoda
M
M
Dodo
K
K
Yamasaki
R
R
Shirai
R
R
Koiso
Y
Y
Miyata
K
K
Kato
F
F
Kato
M
M
Miyachi
H
H
Hashimoto
Y
Y
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010797:Phthalimides / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010797:Phthalimides; D011480:Protease Inhibitors; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex