Rational design, synthesis and pharmacological characterization of novel aminopeptidase A inhibitors.
Bioorg Med Chem Lett
; 113: 129940, 2024 Sep 02.
Article
in En
| MEDLINE
| ID: mdl-39233188
ABSTRACT
Aminopeptidase A (APA) is a membrane-bound zinc metallopeptidase involved in the production of angiotensin III, one effector peptide of the brain renin-angiotensin system, making brain APA a relevant pharmacological target for the development of novel therapeutic treatments against hypertension and heart failure. The structure-based design of new APA inhibitors is described, based on previously developed thiol-containing inhibitors and APA crystal structure. Chemical synthesis, in vitro assessment against APA activity, pharmacological and pharmacokinetic profiling were performed, ultimately leading to a potent and selective APA inhibitor.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Bioorg Med Chem Lett
/
Bioorg. med. chem. lett
/
Bioorganic & medicinal chemistry letters
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Document type:
Article
Country of publication:
United kingdom