R-4066

R-4066

Systematic (IUPAC) name
6-(3,4-dihydro-1'H,2H-spiro[naphthalene-1,4'-piperidin]-1'-yl)-4,4-diphenylhexan-3-one
Identifiers
CAS Number	101564-56-1
PubChem	CID 380029
Synonyms	N-(3,3-diphenyl-4-oxohex-1-yl)-7,8-benzo-3-azaspiro[5.5]undecane
Chemical data
Formula	C32H37NO
Molar mass	451.641
SMILES CCC(=O)C(CCN1CCC2(CCCC3=CC=CC=C32)CC1)(C4=CC=CC=C4)C5=CC=CC=C5
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R-4066 (Spirodone) is a drug which is an analogue of the opioid analgesic methadone, or more accurately Norpipanone, where the metabolically labile dimethylamino group has been replaced by a piperidinospiro group. Developed by Janssen Pharmaceutica,^[1] it is around 212x more potent than methadone as an analgesic in animal tests, with an effective oral dosage of 0.07 mg/kg, but is slightly shorter acting, with a duration of action of around 3 hours. If the ketone function is reduced and acetylated, the (R) isomer of the resultant compound is equipotent and has an analgesic duration of 20.5 hours compared to 8 hours for methadone.^[2]

R-4066 has never been used in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal.

References

1. U.S. Patent 3,125,580
2. Frincke, J. M.; Henderson, G. L.; Janssen, P. A. J.; Van Der Eycken, C. A. M. (1978). "Synthesis and analgesic activity of some long-acting piperidinospiro derivatives of methadone". Journal of Medicinal Chemistry 21 (5): 474–6. doi:10.1021/jm00203a014. PMID 660594.