Gacyclidine

Gacyclidine

Systematic (IUPAC) name
1-[(1R,2S)-2-methyl-1-thiophen-2-ylcyclohexyl]piperidine
Identifiers
CAS Number	68134-81-6
ATC code	none
PubChem	CID 176265
ChemSpider	153540
UNII	9290ND070R
ChEMBL	CHEMBL1742478
Chemical data
Formula	C16H25NS
Molar mass	263.4414 g/mol
SMILES C[C@@H](CCCC1)[C@@]1(N2CCCCC2)C3=CC=CS3
InChI InChI=1S/C16H25NS/c1-14-8-3-4-10-16(14,15-9-7-13-18-15)17-11-5-2-6-12-17/h7,9,13-14H,2-6,8,10-12H2,1H3/t14-,16+/m0/s1 Key:DKFAAPPUYWQKKF-GOEBONIOSA-N
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Gacyclidine^[1] (GK-11)^[2] is a psychoactive drug which acts as a dissociative via functioning as a non-competitive NMDA receptor antagonist. It is closely related to phencyclidine (PCP), and specifically, is a derivative of tenocyclidine (TCP).^[3][4]

Synthesis

The condensation of 2-methylcyclohexanone (I) with 2-thienyllithium (II) or 2-thienylmagnesium bromide (III) gives cyclohexanol (IV) as a diastereomeric mixture, which was treated with sodium azide (NaN₃) in trichloroacetic acid to yield the azide (V). The reduction of (V) with lithium aluminium hydride (LiAlH⁴) or Raney nickel in isopropanol affords the corresponding amine (VI), preferentially with the cis-configuration. Finally, this compound is condensed with 1,5-dibromopentane (VII) by means of potassium carbonate (K₂CO₃) in acetonitrile to provide the target compound as a diastereomeric mixture.^[5]

See also

• Arylcyclohexylamine

References

1. US patent 6107495, Jean-Bernard Cazaux, Michel Dafniet, Jean-Marc Kamenka, Eric Manginot, "Thienylcyclohexane derivatives for thienylcyclohexyl synthesis" 
2. Jacques Hamon, Florence Espaze, Jacques Vignon & Jean-Marc Kamenka (1999). "The search for TCP analogues binding to the low affinity PCP receptor sites in the rat cerebellum". Eur. J. Med. Chem. 34 (2): 125–135. doi:10.1016/S0223-5234(99)80046-4.
3. Hirbec H, Gaviria M, Vignon J. (2001). "Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor". CNS Drug Reviews 7 (2): 172–98. doi:10.1111/j.1527-3458.2001.tb00194.x. PMID 11474423.
4. Hirbec H, Mausset AL, Kamenka JM, Privat A, Vignon J (2002). "Re-evaluation of phencyclidine low-affinity or "non-NMDA" binding sites". J Neurosci Res 68 (3): 305–314. doi:10.1002/jnr.10203. PMID 12111860.
5. US patent 5179109, Jean-Marc Kamenka et al, "Pharmaceutical compositions for neuroprotection containing arylcyclohexylamines"