N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate

<i>N</i>,<i>O</i>-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate

N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate

Chemical compound

N,O-Dimethyl-4β-(2-naphthyl)piperidine-3β-carboxylate (DMNPC) is a piperidine based stimulant drug which is synthesised from arecoline. It is similar to nocaine in chemical structure, and has two and a half times more activity than cocaine as a dopamine reuptake inhibitor. However it is also a potent serotonin reuptake inhibitor, with similar affinity to fluoxetine.[1]

Quick Facts Identifiers, CAS Number ...

Ki Affinity of Piperidine Based MAT Inhibitors
∗∗XN5HTDANE
SSp-VinylMe138131175
p-Ethyl255>1.7K>1.1K
p-Allyl309964>1K
p-Ethynyl175187364
p-Phenyl62173203
β-Naphthyl7.62134
3R,4S42947241
RR1928727
3S,4R1227138
H2Cl3.59030
SS/RRα-NaphthylMe101304281

The stereochemistry of DMNPC dramatically affects it's binding affinity with the SS enantiomer having the highest overall activity. The 3R,4S enantiomer demonstrates the highest selectivity for 5-HTT.

In animal studies, DMNPC exhibits similar potency as fluoxetine but with greater activity for DAT and NET. N-Demethylation of DMNPC has shown to produce a 3-fold increase in potency for 5-HTT.[1]

Synthesis

A racemic mixture of DMNPC can be synthesized from freebase arecoline in a grignard reaction with 2-naphthylmagnesium bromide. Further reactions and separation methods can be used to produce enantiomerically pure products.[1]


A substantially simpler method that ablates the carbomethoxy ester substituent has been demonstrated by D. Koch in Ex2: U.S. patent 6,303,627

See also

References

  1. [1]
    Tamiz AP, Zhang J, Flippen-Anderson JL, Zhang M, Johnson KM, Deschaux O, et al. (March 2000). "Further SAR Studies of Piperidine-Based Analogues of Cocaine. 2. Potent Dopamine and Serotonin Reuptake Inhibitors". Journal of Medicinal Chemistry. 43 (6): 1215–22. doi:10.1021/jm9905561. PMID 10737754.
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