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-inhibitory activity.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Shimazawa
authors.forename: H
authors.initials: H
authors.lastname: Takayama
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Komoda
authors.forename: K
authors.initials: K
authors.lastname: Dodo
authors.forename: R
authors.initials: R
authors.lastname: Yamasaki
authors.forename: R
authors.initials: R
authors.lastname: Shirai
authors.forename: Y
authors.initials: Y
authors.lastname: Koiso
authors.forename: K
authors.initials: K
authors.lastname: Miyata
authors.forename: F
authors.initials: F
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Miyachi
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D010797:Phthalimides; D011480:Protease Inhibitors; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex