Identification of 1-Methyl-<i>N</i>-(propan-2-yl)-<i>N</i>-({2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1<i>H</i>-imidazole-4-carboxamide as a Potent and Orally Available Glycine Transporter 1 Inhibitor

Abstract

We previously identified 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-

Glycine-induced NMDA receptor internalization provides neuroprotection and preserves vasculature following ischemic stroke

“…A recent review suggests that glycine and d -serine may be therapeutically beneficial by down regulating NMDARs, such as rodent models of traumatic brain injury and lipopolysaccharide-induced neuroinflammation ( Biegon et al., 2018 ). There is also a growing body of evidence to suggest that extracellular glycine is neuroprotective in several rodent ischemic stroke models ( Huang et al., 2016 ; Zheng et al., 2017 ; Zhao et al., 2018 ; Liu et al., 2019 ; Chen et al., 2020 ; Yamamoto et al., 2016 ). Moreover, the level of extracellular glycine appears to be important in stroke outcome.…”

Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity

“…Since the seminal preparation of the trifluoromethoxy group by Yagupolskii in 1955 [ 1 ], the interest in this very specific organic moiety has grown continuously, in particular for life sciences purposes [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Such interest can be explained by the conjunction of its multiple advantages: the “pseudohalogen” character of this entity which makes it comparable to a fluorine atom in terms of electronic properties, and the deep modifications of the conformation as well as the physico-chemical behavior induced in molecules linked to this group [ 10 , 11 , 12 , 13 , 14 ].…”