1366404-68-3

Upstream product

• 118289-17-1 2-bromopyridine-4-carboxaldehyde 
• 1289386-60-2 N-[(2-bromopyridin-4-yl)methyl]propan-2-amine 
• 1365879-47-5 N-[(2-bromopyridin-4-yl)methyl]-1-methyl-N-(propan-2-yl)-1H-imidazole-4-carboxamide 
• 768-35-4 3-fluorophenylboronic acid 

Relevant academic research and scientific papers

Identification of 1-methyl-N-(propan-2-yl)-N-({2-[4-(trifluoromethoxy)-phenyl]pyridin-4-yl}methyl)-1H-imidazole-4-carboxamide as a potent and orally available glycine transporter 1 inhibitor

We previously identified 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidine-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (5, TP0439150) as a potent and orally available glycine transporter 1 (GlyT1) inhibitor. In this article, we describe our identification of 1-methyl-N-(propan-2-yl)-N-({2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1H-imidazole-4-carboxamide (7n) as a structurally diverse back-up compound of 5, using central nervous system multiparameter optimization (CNS MPO) as a druglikeness guideline. Compound 7n showed a higher CNS MPO score and different physicochemical properties as compared to 5. Compound 7n exhibited potent GlyT1 inhibitory activity, a favorable pharmacokinetics profile, and elicited an increase in the cerebrospinal fluid (CSF) concentration of glycine in rats.

GLYCINE TRANSPORTER INHIBITING SUBSTANCES

The present invention aims to provide novel compounds of formula [I] or pharmaceutically acceptable salts thereof that are based on a glycine uptake inhibiting action and which are useful in the prevention or treatment of such diseases as schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, posttraumatic stress disorder, specific phobia, acute stress disorder, etc.), depression, drug addiction, spasm, tremor, pain, and sleep disorder: