4-Aminoquinolines as a novel class of NR1/2B subtype selective NMDA receptor antagonists

Discovery of 3-Substituted Aminocyclopentanes as Potent and Orally Bioavailable NR2B Subtype-Selective NMDA Antagonists

“…Interestingly, the more polarized 1,3,4-thiadiazole caused 36 to become a substrate for human and rat Pgp efflux (MRD1 and mdr1a BÀA/AÀB ratio = 5.6 and 8.6, respectively). A better balance between potency, selectivity, and Pgp liability was obtained by preparing the isomeric 5-substituted-1,2,4-oxadiazole (37). Though slightly less potent (K i = 1.4 nM) and selective (hERG IP = 12.5 μM) than 22, compound 37 was not a substrate for human and rat Pgp efflux (MRD1 and mdr1a BÀA/AÀB ratio = 0.9 and 2.1, respectively) and was advanced into the ex vivo receptor occupancy study.…”

Regioselective alkynylation of 2-aryl-4-chloro-3-iodoquinolines and subsequent arylation or amination of the 2-aryl-3-(alkynyl)-4-chloroquinolines

“…31 The analogous 4-amino-2-arylquinolines have also been found to represent a novel class of NR1/2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonists. 32 …”

One-Pot Synthesis of 2,3,4-Triarylquinolines via Suzuki-Miyaura Cross-Coupling of 2-Aryl-4-chloro-3-iodoquinolines with Arylboronic Acids

“…We isolated the corresponding primary 4-amino 2,3-diarylquinolines 4 with potential antimalarial [16-18], anti-inflammatory [ 19 ], and antihypertensive activities [ 20 ]. The primary 4-amino-2-arylquinolines also represent a novel class of NR1/2B subtype selective N -methyl-D-aspartate (NMDA) receptor antagonists [ 21 ].…”