Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression was written by Nirogi, Ramakrishna;Mohammed, Abdul Rasheed;Shinde, Anil K.;Ravella, Srinivasa Rao;Bogaraju, Narsimha;Subramanian, Ramkumar;Mekala, Venkat Reddy;Palacharla, Raghava Choudary;Muddana, Nageswararao;Thentu, Jagadeesh Babu;Bhyrapuneni, Gopinadh;Abraham, Renny;Jasti, Venkat. And the article was included in Journal of Medicinal Chemistry in 2020.Electric Literature of C5H5NO This article mentions the following:
A series of chem. optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride, I, (SUVN-911) as a clin. candidate. Compound I is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bio-available and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development. In the experiment, the researchers used many compounds, for example, Pyridin-4-ol (cas: 626-64-2Electric Literature of C5H5NO).
Pyridin-4-ol (cas: 626-64-2) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Electric Literature of C5H5NO