Design, Synthesis, and Biological Evaluation of Novel Heteroaryl, Squaramide, and Indolcarboxamide Derivatives as Formyl Peptide Receptor 2 Agonists to Target Neuroinflammation.

ABSTRACT: Recent research reveals Formyl Peptide Receptor 2 (FPR2) as a relevant G Protein-Coupled Receptor involved in the resolution phase of inflammation. Therefore, FPR2 agonists are promising agents to tackle neuroinflammatory-based diseases, such as Alzheimer's Disease or Autism Spectrum Disorder. Here, we describe the synthesis and biological evaluation of novel FPR2 agonists designed through the bioisosteric replacement of the phenyl urea function in the potent FPR2 agonist (S)-1-(3-(4-cyanophenyl)-1-(indolin-1-yl)-1-oxopropan-2-yl)-3-(4-fluorophenyl)urea (5), obtaining novel heteroaryl, squaramide, and indolcarboxamide derivatives. The structural modification had a profound effect on FPR2 agonist potency, metabolic stability, aqueous solubility, and cell permeability, resulting in co

SUBMITTER: Francavilla F 

PROVIDER: S-EPMC12906792 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature