Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration
Laboratory studyHumansOther animals
- Design
- Laboratory study
- Subjects
- Human NAAA enzyme assays; in vivo animal testing (species not stated in the abstract)
- Dose used in the study
- Not applicable; no palmitoylethanolamide was given. The test compounds are NAAA inhibitors
- Duration
- Not stated in the abstract
- What was measured
- Inhibition of human NAAA by a series of pyrazole azabicyclo[3.2.1]octane sulfonamides, their structure-activity relationships, and the biochemical, in vitro and in vivo drug-like profile of the lead compound.
What the authors reported
The authors identified compound 50 (ARN19689), which inhibited human NAAA at low nanomolar concentration (IC50 0.042 micromolar) by a non-covalent mechanism and was systemically available. NAAA breaks down palmitoylethanolamide, so its inhibition is meant to preserve the body's own PEA. No efficacy data in disease models are given in the abstract.
Limits of this study
A medicinal chemistry and enzyme study; it cannot show effect in people or animals treated in practice. PEA itself was not given. Several authors are inventors on patents for these compounds, owned by Fondazione Istituto Italiano di Tecnologia.
Source
PubMed 34469137 · doi:10.1021/acs.jmedchem.1c00575
Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.