132974-83-5Relevant articles and documents
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
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
, p. 2833 - 2853 (2020)
A series of chemical 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 (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable 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.
Practical Synthesis of Chiral N-Heterocyclic Carbene Triazolium Salts Containing a Hydroxy Functional Handle
Dhayalan, Vasudevan,Mal, Kanchan,Milo, Anat
, p. 2845 - 2864 (2019/07/04)
A library of functionalized chiral pyrrolidine-based N-heterocyclic carbene triazolium salts containing a hydroxy handle is prepared from readily accessible chiral (S)-pyroglutamic acid in eight steps. This improved synthetic protocol affords increased yields for known structures and 18 new NHCs are prepared by this method. The presence of a hydroxy handle offers potential for further functionalization and for non-covalent control over catalytic reactions in which the NHCs can serve as organocatalysts or ligands for organometallic catalysis.
BACTERIAL EFFLUX PUMP INHIBITORS
-
Page/Page column 58; 59, (2018/09/28)
Disclosed herein are compounds of formula I and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.
