Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors
Laboratory studyOther animals
- Design
- Laboratory study
- Subjects
- Enzyme assays plus a mouse or rat model of lipopolysaccharide-induced acute lung injury; species and numbers not stated in the abstract
- Dose used in the study
- No palmitoylethanolamide was given; pyrrolidine amide NAAA inhibitors, compound 4g (E93) in vivo, dose not stated
- Duration
- Not stated in the abstract
- What was measured
- Potency and selectivity of new NAAA inhibitors over FAAH; mechanism of inhibition; anti-inflammatory activity in acute lung injury and its blockade by the PPAR-alpha antagonist MK886
What the authors reported
The study found:
- Small lipophilic 3-phenyl substituents gave the best potency; flexible linkers raised potency but cut selectivity over FAAH.
- Several low-micromolar inhibitors were made.
- Compound 4g inhibited NAAA competitively and reversibly and showed high anti-inflammatory activity in acute lung injury, which MK886 blocked.
Limits of this study
A chemistry and animal-model study of compounds that stop PEA breakdown; PEA itself was not given and it cannot show effect in people. Funding and conflicts not stated in the abstract.
Source
PubMed 30931090 · doi:10.1039/c8md00432c
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.