Eclanamine (U-48,753) is a drug which was patented as an antidepressant, but was never marketed. It acts by inhibiting the reuptake of serotonin and norepinephrine. Eclanamine was discovered by accident as a derivative of the κ-opioid receptor agonist U-50,488.
§Synthesis
Some alicyclic 1,2-diamine derivatives have recently been shown to have interesting CNS properties. For example, eclanamine (5) is an antidepressant with a rapid onset of action. The reasons for its potency are not as yet clear but pharmacologists note that the drug desensitizes adrenergic alpha-2 receptors and antagonizes the actions of clonidine.
The synthesis of eclanamine starts with attack of cyclopentene oxide (1>) by dimethylamine (to give 2). This product is converted to the mesylate by reaction with sodium hydride followed by mesyl chloride. Attack of the product (3) by 3,4-dichloroaniline leads to trans-diamine 4. The stereochemical outcome represents a double rear side displacement. The synthesis is completed by acylation with propionic anhydride to give eclanamine (5),
§See also
- U-50,488
- Bromadoline
§References
