A series of chemical optimizations guided by in vitro affinity at α4β2 receptor in combination with selectivity against α3β4 receptor, pharmacokinetic evaluation and in vivo efficacy in 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 Ki value of 1.5 nM. It showed >10 µM binding affinity towards 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 supports 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.