Synthesis, Evaluation and Proposed Binding Pose of Substituted Spiro-Oxindole Dihydroquinazolinones as IRAP Inhibitors.
Animals
Binding Sites
Cystinyl Aminopeptidase
/ antagonists & inhibitors
Drug Evaluation, Preclinical
Humans
Models, Molecular
Oxindoles
/ chemical synthesis
Protease Inhibitors
/ chemical synthesis
Protein Binding
Protein Conformation
Quinazolinones
/ chemical synthesis
Rats
Receptors, Angiotensin
/ metabolism
Solubility
Structure-Activity Relationship
enzymes
inhibitors
insulin-regulated aminopeptidases
preclinical profiling
spiro compounds
Journal
ChemistryOpen
ISSN: 2191-1363
Titre abrégé: ChemistryOpen
Pays: Germany
ID NLM: 101594811
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
22
11
2019
revised:
23
01
2020
entrez:
11
3
2020
pubmed:
11
3
2020
medline:
11
3
2020
Statut:
epublish
Résumé
Insulin-regulated aminopeptidase (IRAP) is a new potential macromolecular target for drugs aimed for treatment of cognitive disorders. Inhibition of IRAP by angiotensin IV (Ang IV) improves the memory and learning in rats. The majority of the known IRAP inhibitors are peptidic in character and suffer from poor pharmacokinetic properties. Herein, we present a series of small non-peptide IRAP inhibitors derived from a spiro-oxindole dihydroquinazolinone screening hit (pIC
Identifiants
pubmed: 32154052
doi: 10.1002/open.201900344
pii: OPEN201900344
pmc: PMC7050655
doi:
Substances chimiques
Oxindoles
0
Protease Inhibitors
0
Quinazolinones
0
Receptors, Angiotensin
0
Cystinyl Aminopeptidase
EC 3.4.11.3
leucyl-cystinyl aminopeptidase
EC 3.4.11.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
325-337Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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