N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate
Identifiers
  • methyl (3S,4S)- 1-methyl- 4-(2-naphthyl)piperidine- 3-carboxylate
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H21NO2
Molar mass283.371 g·mol−1
3D model (JSmol)
  • COC(=O)C1CN(C)CCC1c3ccc2ccccc2c3
  (verify)

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]

Ki Affinity of Piperidine Based MAT Inhibitors
∗∗ X N 5HT DA NE
SS p-Vinyl Me 138 131 175
p-Ethyl 255 >1.7K >1.1K
p-Allyl 309 964 >1K
p-Ethynyl 175 187 364
p-Phenyl 62 173 203
β-Naphthyl 7.6 21 34
3R,4S 42 947 241
RR 192 87 27
3S,4R 12 271 38
H2Cl 3.5 90 30
SS/RR α-Naphthyl Me 101 304 281

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. ^ a b c 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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