NLX-204


NLX-204 is a drug that as of 2026 is being evaluated to treat depression. It is a selective biased agonist of the serotonin 5-HT1A receptor, distinguished by its preference for activating ERK1/ERK2 phosphorylation pathways.
This compound has demonstrated potent and rapid-acting antidepressant-like effects in preclinical models, with activity comparable to ketamine in reversing symptoms of depression and treatment-resistant depression in rodents. Recent studies suggest that NLX-204 also offers potential benefits reversing memory deficits and anxiety, positioning it as a candidate for a rapid-acting antidepressant therapy.

Chemistry

Synthesis

NLX-204 is synthesized from 3-chloro-4-fluorobenzoic acid. Conversion to the corresponding benzoyl chloride followed by amidation with 4-piperidone yields a benzoylpiperidone intermediate. A Darzens reaction with chloroacetonitrile produces a cyanoepoxide, which undergoes regioselective ring opening with polypyridine to form a cyanohydrin. Final reductive amination with 2-ethanamine in the presence of sodium cyanoborohydride affords NLX-204.