749200-45-1Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of novel pyrrolidinone small-molecule Formyl peptide receptor 2 agonists
Chapman, Timothy M.,Ferraro, Bartolo,Garrido-Mesa, Jose,Maas, Sanne L.,Maciuszek, Monika,Merritt, Andy,Nicolaes, Gerry A. F.,Ortega-Gomez, Almudena,Perretti, Mauro,Soehnlein, Oliver
, (2021)
A series of Formyl peptide receptor 2 small molecule agonists with a pyrrolidinone scaffold, derived from a combination of pharmacophore modelling and docking studies, were designed and synthesized. The GLASS (GPCR-Ligand Association) database was screened using a pharmacophore model. The most promising novel ligand structures were chosen and then tested in cellular assays (calcium mobilization and β-arrestin assays). Amongst the selected ligands, two pyrrolidinone compounds (7 and 8) turned out to be the most active. Moreover compound 7 was able to reduce the number of adherent neutrophils in a human neutrophil static adhesion assay which indicates its anti-inflammatory and proresolving properties. Further exploration and optimization of new ligands showed that heterocyclic rings, e.g. pyrazole directly connected to the pyrrolidinone scaffold, provide good stability and a boost in the agonistic activity. The compounds of most interest (7 and 30) were tested in an ERK phosphorylation assay, demonstrating selectivity towards FPR2 over FPR1. Compound 7 was examined in an in vivo mouse pharmacokinetic study. Compound 7 may be a valuable in vivo tool and help improve understanding of the role of the FPR2 receptor in the resolution of inflammation process.
Efficient synthesis of N-benzyl-3-aminopyrrolidine-2,5-dione and N-benzyl-3-aminopyrrolidin-2-one
Vo-Hoang, Yen,Gasse, Cécile,Vidal, Michel,Garbay, Christiane,Galons, Hervé
, p. 3603 - 3605 (2007/10/03)
Reaction of N-tert-butyloxycarbonylasparagine (Boc-Asn) with 2equiv of benzyl bromide in presence of cesium carbonate led to N-benzyl-3-Boc-amino- pyrrolidin-2,5-dione 1a (N-benzyl-3-Boc-aminosuccinimide). Borane dimethylsulfide reduced 3-Boc-aminopyrrolidine-2,5-dione 1a into 3-Boc-aminopyrrolidin-2-one 2a. The same procedure could also be used to prepare derivatives 1 and 2 substituted on the aromatic ring.
