94915-11-4Relevant articles and documents
Discovery of Dihydropyrrolo[1,2- a]pyrazin-3(4 H)-one-Based Second-Generation GluN2C- And GluN2D-Selective Positive Allosteric Modulators (PAMs) of the N-Methyl- d -Aspartate (NMDA) Receptor
Epplin, Matthew P.,Mohan, Ayush,Harris, Lynnea D.,Zhu, Zongjian,Strong, Katie L.,Bacsa, John,Le, Phuong,Menaldino, David S.,Traynelis, Stephen F.,Liotta, Dennis C.,Liotta, Dennis C.
, p. 7569 - 7600 (2020/08/21)
The N-methyl-d-aspartate receptor (NMDAR) is an ion channel that mediates the slow, Ca2+-permeable component of glutamatergic synaptic transmission in the central nervous system (CNS). NMDARs are known to play a significant role in basic neurological functions, and their dysfunction has been implicated in several CNS disorders. Herein, we report the discovery of second-generation GluN2C/D-selective NMDAR-positive allosteric modulators (PAMs) with a dihydropyrrolo[1,2-a]pyrazin-3(4H)-one core. The prototype, R-(+)-EU-1180-453, exhibits log unit improvements in the concentration needed to double receptor response, lipophilic efficiency, and aqueous solubility, and lowers cLogP by one log unit compared to the first-generation prototype CIQ. Additionally, R-(+)-EU-1180-453 was found to increase glutamate potency 2-fold, increase the response to maximally effective concentration of agonist 4-fold, and the racemate is brain-penetrant. These compounds are useful second-generation in vitro tools and a promising step toward in vivo tools for the study of positive modulation of GluN2C- and GluN2D-containing NMDA receptors.
Enantioselective synthesis of (S)-calycotomine employing catalytic asymmetric hydrogenation with an iridium(I)-(R)-BINAP-phthalimide complex
Morimoto, Toshiaki,Suzuki, Naoaki,Achiwa, Kazuo
, p. 183 - 187 (2007/10/03)
An optically active 1-hydroxymethyl-substituted tetrahydroisoquinoline alkaloid, (S)-calycotomine 1, was conveniently synthesized by using catalytic asymmetric hydrogenation of 1-benzyloxymethyl-3,4-dihydro-6,7-dimethoxyisoquinoline 6 with 0.5 mol % of an