1622235-91-9Relevant academic research and scientific papers
Stereoselective Synthesis of New (2 S,3 R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors
Bunch, Lennart,Hansen, Jacob C.,Hansen, Kasper B.,Iliadis, Stylianos,Kayser, Silke,Krogsgaard-Larsen, Niels,Larsen, Younes,Moroz, Aleksandra,Nielsen, Birgitte,Pickering, Darryl S.,Staudt, Markus,Syrenne, Jed T.,Temperini, Piero,Yi, Feng
, (2020/03/10)
Competitive antagonists for ionotropic glutamate receptors (iGluRs) are highly valuable tool compounds for studying health and disease states in the central nervous system. However, only few subtype selective tool compounds are available and the discovery of antagonists with novel iGluR subtype selectivity profiles remains a profound challenge. In this paper, we report an elaborate structure-activity relationship (SAR) study of the parental scaffold 2,3-trans-3-carboxy-3-phenyl-proline by the synthesis of 40 new analogues. Three synthetic strategies were employed with two new strategies of which one being a highly efficient and fully enantioselective strategy based on C(sp3)-H activation methodology. The SAR study led to the conclusion that selectivity for the NMDA receptors was a general trend when adding substituents in the 5′-position. Selective NMDA receptor antagonists were obtained with high potency (IC50 values as low as 200 nM) and 3-34-fold preference for GluN1/GluN2A over GluN1/GluN2B-D NMDA receptors.
PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES AS IGLUR ANTAGONISTS
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Page/Page column 27; 29, (2014/09/03)
The present invention relates to compounds of Formula (I), combinations and use thereof for disease therapy, or pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoismers and polymorphs thereof, which are iGlu R inhibitors, and hence are useful in the treatment of psychiatric diseases or neurological disorders or a disease or disorder associated with abnormal activities of iGluR receptors.
