Substituted cathinone

Cathinone

General chemical structure of substituted cathinones, with R₁-R₄ defined in text

Substituted cathinones, which include some stimulants and entactogens, are derivatives of cathinone. They feature a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon, along with additional substitutions. Cathinone occurs naturally in the plant khat whose leaves are chewed as a recreational drug.^[1]

Chemical derivatives

The derivatives may be produced by substitutions at four locations of the cathinone molecule:

• R₁ = hydrogen, or any combination of one or more alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents
• R₂ = hydrogen or any alkyl group
• R₃ = hydrogen, any alkyl group, or incorporation in a cyclic structure
• R₄ = hydrogen, any alkyl group, or incorporation in a cyclic structure

The following table displays notable derivatives that have been reported:

Compound	R1	R2	R3	R4
Cathinone	H	Me	H	H
Methcathinone	H	Me	H	Me
Ethcathinone	H	Me	H	Et
Buphedrone	H	Et	H	Me
NEB	H	Et	H	Et
Pentedrone	H	nPr	H	Me
NEP	H	nPr	H	Et
Hexedrone	H	nBu	H	Me
NEH	H	nBu	H	Et
Octedrone	H	hexyl	H	Me
Dimethylcathinone	H	Me	Me	Me
Diethylpropion	H	Me	Et	Et
Bupropion (3-CBP)	3-Cl	Me	H	t-Bu
Mephedrone	4-Me	Me	H	Me
2-MMC	2-Me	Me	H	Me
2-MEC	2-Me	Me	H	Et
2-EEC	2-Et	Me	H	Et
3-MMC	3-Me	Me	H	Me
3-MEC	3-Me	Me	H	Et
3-EMC	3-Et	Me	H	Me
3-EEC	3-Et	Me	H	Et
4-EMC	4-Et	Me	H	Me
4-EEC	4-Et	Me	H	Et
4-MC	4-Me	Me	H	H
Benzedrone	4-Me	Me	H	Bn
2'-MeO-Benzedrone	4-Me	Me	H	2-MeO-Bn
4-MEC	4-Me	Me	H	Et
4-MPC	4-Me	Me	H	nPr
N,N-DMMC	4-Me	Me	Me	Me
N,N-MEMC	4-Me	Me	Me	Et
N,N-DEMC	4-Me	Me	Et	Et
EDMC	4-Et	Me	Me	Me
2,4-DMMC	2,4-dimethyl	Me	H	Me
2,4-DMEC	2,4-dimethyl	Me	H	Et
3,4-DMMC	3,4-dimethyl	Me	H	Me
3,4-DMEC	3,4-dimethyl	Me	H	Et
2,4,5-TMMC	2,4,5-trimethyl	Me	H	Me
2,4,5-TMOMC	2,4,5-trimethoxy	Me	H	Me
3,4,5-TMOMC	3,4,5-trimethoxy	Me	H	Me
Methedrone	4-MeO	Me	H	Me
Dimethedrone	4-MeO	Me	Me	Me
Ethedrone	4-MeO	Me	H	Et
2-MOMC	2-MeO	Me	H	Me
3-MOMC	3-MeO	Me	H	Me
3-FC	3-F	Me	H	H
4-FC	4-F	Me	H	H
2-FMC	2-F	Me	H	Me
2-FEC	2-F	Me	H	Et
3-FMC	3-F	Me	H	Me
3-FEC	3-F	Me	H	Et
2-CMC	2-Cl	Me	H	Me
Clophedrone	3-Cl	Me	H	Me
3-CEC	3-Cl	Me	H	Et
3-BMC	3-Br	Me	H	Me
Flephedrone	4-F	Me	H	Me
4-FEC	4-F	Me	H	Et
Clephedrone	4-Cl	Me	H	Me
4-CEC	4-Cl	Me	H	Et
4-CiPC	4-Cl	Me	H	iPr
4-CDMC	4-Cl	Me	Me	Me
Brephedrone	4-Br	Me	H	Me
4-BEC	4-Br	Me	H	Et
4-EFMC	4-(2-fluoroethyl)	Me	H	Me
4-MSMC	4-SO2Me	Me	H	Me
4-PHMC	4-phenyl	Me	H	Me
Mexedrone	4-Me	methoxymethyl	H	Me
FMMC	3-F-4-Me	Me	H	Me
MMOMC	3-Me-4-MeO	Me	H	Me
3,4-DCMC	3,4-dichloro	Me	H	Me
3,5-DCMC	3,5-dichloro	Me	H	Me
3,5-DFMC	3,5-difluoro	Me	H	Me
2,5-DMOMC	2,5-dimethoxy	Me	H	Me
βk-2C-B	2,5-dimethoxy-4-bromo	H	H	H
βk-2C-I	2,5-dimethoxy-4-iodo	H	H	H
βk-DOB	2,5-dimethoxy-4-bromo	Me	H	H
βk-MDOM	2,5-dimethoxy-4-methyl	Me	H	Me
βk-MDA	3,4-methylenedioxy	Me	H	H
N-acetyl-βk-MDA	3,4-methylenedioxy	Me	H	acetyl
2,3-MDMC	2,3-methylenedioxy	Me	H	Me
Methylone	3,4-methylenedioxy	Me	H	Me
Dimethylone	3,4-methylenedioxy	Me	Me	Me
N-acetyl-methylone	3,4-methylenedioxy	Me	acetyl	Me
N-hydroxy-methylone	3,4-methylenedioxy	Me	hydroxy	Me
Ethylone	3,4-methylenedioxy	Me	H	Et
Diethylone	3,4-methylenedioxy	Me	Et	Et
N-acetyl-ethylone	3,4-methylenedioxy	Me	acetyl	Et
MDPT	3,4-methylenedioxy	Me	H	t-Bu
BMDP	3,4-methylenedioxy	Me	H	Bn
3,4-EDMC	3,4-ethylenedioxy	Me	H	Me
βk-IMP	3,4-trimethylene	Me	H	Me
βk-IBP	3,4-trimethylene	Et	H	Et
βk-IVP	3,4-trimethylene	nPr	H	Et
3-Fluorobuphedrone	3-F	Et	H	Me
4-Fluorobuphedrone	4-F	Et	H	Me
4-Bromobuphedrone	4-Br	Et	H	Me
4-MeMABP	4-Me	Et	H	Me
4-Me-NEB	4-Me	Et	H	Et
4-F-NEB	4-F	Et	H	Et
4-Me-DMB	4-Me	Et	Me	Me
3,4-DMEB	3,4-dimethyl	Et	H	Et
4-Methoxybuphedrone	4-MeO	Et	H	Me
Butylone	3,4-methylenedioxy	Et	H	Me
Eutylone	3,4-methylenedioxy	Et	H	Et
βk-PBDB	3,4-methylenedioxy	Et	H	nPr
Bn-4-MeMABP	4-Me	Et	H	Bn
BMDB	3,4-methylenedioxy	Et	H	Bn
βk-DMBDB	3,4-methylenedioxy	Et	Me	Me
βk-MMDMA	3,4-methylenedioxy-5-MeO	Me	H	Me
βk-MMDMA-2	2-MeO-3,4-methylenedioxy	Me	H	Me
βk-DMMDA	2,5-diMeO-3,4-methylenedioxy	Me	H	H
5-Methylmethylone	3,4-methylenedioxy-5-Me	Me	H	Me
5-Methylethylone	3,4-methylenedioxy-5-Me	Me	H	Et
2-Methylbutylone	2-Me-3,4-methylenedioxy	Et	H	Me
5-Methylbutylone	3,4-methylenedioxy-5-Me	Et	H	Me
Pentylone	3,4-methylenedioxy	nPr	H	Me
N-ethylpentylone	3,4-methylenedioxy	nPr	H	Et
N-propylpentylone	3,4-methylenedioxy	nPr	H	nPr
MMP	4-Me	nPr	H	Me
MEP	4-Me	nPr	H	Et
3,4-DMEP	3,4-dimethyl	nPr	H	Et
4-F-Pentedrone	4-F	nPr	H	Me
4-Methylpentedrone	4-Me	nPr	H	Me
DL-4662	3,4-dimethoxy	nPr	H	Et
4-F-iPr-norpentedrone	4-F	nPr	H	iPr
4-methylhexedrone	4-Me	nBu	H	Me
4-F-hexedrone	4-F	nBu	H	Me
4-F-octedrone	4-F	hexyl	H	Me
α-phenylmephedrone	4-Me	phenyl	H	Me
"NRG-3"	β-naphthyl instead of phenyl	Me	H	Me
βk-Methiopropamine	thiophen-2-yl instead of phenyl	Me	H	Me
βk-5-MAPB	benzofuran-5-yl instead of phenyl	Me	H	Me
βk-6-MAPB	benzofuran-6-yl instead of phenyl	Me	H	Me
α-Phthalimidopropiophenone	H	Me	phthalimido
PPPO	H	Me	piperidinyl
PPBO	H	Et	piperidinyl
FPPVO	4-F	nPr	piperidinyl
MDPV-azepane	3,4-methylenedioxy	nPr	azepane
α-PPP	H	Me	pyrrolidinyl
α-PBP	H	Et	pyrrolidinyl
α-PVP (O-2387)	H	nPr	pyrrolidinyl
α-PHP	H	nBu	pyrrolidinyl
α-PEP (α-PHPP)	H	nPe	pyrrolidinyl
α-POP	H	hexyl	pyrrolidinyl
α-PNP	H	heptyl	pyrrolidinyl
2-MePPP	2-Me	Me	pyrrolidinyl
3-MePPP	3-Me	Me	pyrrolidinyl
4-MePPP	4-Me	Me	pyrrolidinyl
MOPPP	4-MeO	Me	pyrrolidinyl
3-F-PPP	3-F	Me	pyrrolidinyl
FPPP	4-F	Me	pyrrolidinyl
Cl-PPP	4-Cl	Me	pyrrolidinyl
2,4-DMPPP	2,4-dimethyl	Me	pyrrolidinyl
MPBP	4-Me	Et	pyrrolidinyl
FPBP	4-F	Et	pyrrolidinyl
3-MPBP	3-Me	Et	pyrrolidinyl
3-F-PBP	3-F	Et	pyrrolidinyl
EPBP	4-Et	Et	pyrrolidinyl
MOPBP	4-MeO	Et	pyrrolidinyl
O-2384	3,4-dichloro	Et	pyrrolidinyl
Pyrovalerone (O-2371)	4-Me	nPr	pyrrolidinyl
MPHP	4-Me	nBu	pyrrolidinyl
MPEP	4-Me	pentyl	pyrrolidinyl
α-Phenylpyrovalerone	4-Me	phenyl	pyrrolidinyl
FPVP	4-F	nPr	pyrrolidinyl
4-Cl-PVP	4-Cl	nPr	pyrrolidinyl
4-Br-PVP	4-Br	nPr	pyrrolidinyl
MOPVP	4-MeO	nPr	pyrrolidinyl
DMOPVP	3,4-dimethoxy	nPr	pyrrolidinyl
DMPVP	3,4-dimethyl	nPr	pyrrolidinyl
O-2390	3,4-dichloro	nPr	pyrrolidinyl
O-2494	4-Me	iBu	pyrrolidinyl
4F-PV8	4-F	pentyl	pyrrolidinyl
4F-PV9	4-F	hexyl	pyrrolidinyl
4-MeO-PV8	4-MeO	pentyl	pyrrolidinyl
4-MeO-PV9	4-MeO	hexyl	pyrrolidinyl
MDPPP	3,4-methylenedioxy	Me	pyrrolidinyl
MDMPP	3,4-methylenedioxy	α,α-di-Me	pyrrolidinyl
MDPBP	3,4-methylenedioxy	Et	pyrrolidinyl
MDPV	3,4-methylenedioxy	nPr	pyrrolidinyl
2,3-MDPV	2,3-methylenedioxy	nPr	pyrrolidinyl
5-Me-MDPV	3,4-methylenedioxy-5-Me	nPr	pyrrolidinyl
6-Me-MDPV	2-Me-4,5-methylenedioxy	nPr	pyrrolidinyl
6-MeO-MDPV	2-MeO-4,5-methylenedioxy	nPr	pyrrolidinyl
Br-MeO-MDPV	2,3-methylenedioxy-4-MeO-5-Br	nPr	pyrrolidinyl
MDPHP	3,4-methylenedioxy	nBu	pyrrolidinyl
5-PPDI	3,4-trimethylene	Et	pyrrolidinyl
5-BPDI	3,4-trimethylene	nPr	pyrrolidinyl
5-HPDI	3,4-trimethylene	nBu	pyrrolidinyl
IPPV	3,4-trimethylene	phenyl	pyrrolidinyl
TH-PVP	3,4-tetramethylene	nPr	pyrrolidinyl
TH-PHP	3,4-tetramethylene	nBu	pyrrolidinyl
5-DBFPV	2,3-dihydrobenzofuran-5-yl instead of Ph	nPr	pyrrolidinyl
Naphyrone (O-2482)	β-naphthyl instead of phenyl	nPr	pyrrolidinyl
α-Naphyrone	α-naphthyl instead of phenyl	nPr	pyrrolidinyl
α-PPT	thiophen-2-yl instead of phenyl	Me	pyrrolidinyl
α-PBT	thiophen-2-yl instead of phenyl	Et	pyrrolidinyl
α-PVT	thiophen-2-yl instead of phenyl	nPr	pyrrolidinyl

Legality

On 2 April 2010, the Advisory Council on the Misuse of Drugs in the UK announced that a broad structure-based ban of this entire class of compounds would be instituted, following extensive publicity around grey-market sales and recreational use of mephedrone, a common member of the family. This ban covers compounds with the aforementioned general structure, with 28 compounds specifically named.^[2]

"Any compound (not being bupropion or a substance for the time being specified in paragraph 2.2) structurally derived from 2-amino-1-phenyl-1-propanone by modification in any of the following ways, that is to say,

(i) by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;

(ii) by substitution at the 3-position with an alkyl substituent;

(iii) by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure."

— ACMD, 2 April 2010

This text was added as an amendment to the Misuse of Drugs Act 1971, to come into force on 16 April 2010.^[3] Note that four of the above compounds (cathinone, methcathinone, diethylpropion and pyrovalerone) were already illegal in the UK at the time the ACMD report was issued. Two compounds were specifically excluded from the ban, these being bupropion because of its common use in medicine and relative lack of abuse potential, and naphyrone because its structure falls outside the generic definition and not enough evidence was yet available to justify a ban.

Naphyrone analogues were subsequently banned in July 2010 following a further review by the ACMD,^[4][5] along with a further broad based structure ban even more expansive than the last.^[6][7]

“Any compound structurally derived from 2–aminopropan–1–one by substitution at the 1-position with any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), whether or not the compound is

further modified in any of the following ways, that is to say—

(i) by substitution in the ring system to any extent with alkyl, alkoxy, haloalkyl or halide substituents, whether or not further substituted in the ring system by one or more other univalent substituents;

(ii) by substitution at the 3–position with an alkyl substituent;

(iii) by substitution at the 2-amino nitrogen atom with alkyl or dialkyl groups, or

by inclusion of the 2-amino nitrogen atom in a cyclic structure.”

— Home Office, 13th July 2010.

General chemical structure of substituted naphyrones, with R₁-R₃ defined in text

The substitutions in the general structure for naphyrone analogues subject to the ban may be described as follows:

• Cyc = any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), including analogues where the ring system is substituted to any extent with alkyl, alkoxy, haloalkyl or halide substituents, whether or not further substituted in the ring system by one or more other univalent substituents
• R₁ = hydrogen or any alkyl group
• R₂ = hydrogen, any alkyl group, or incorporation in a cyclic structure
• R₃ = hydrogen, any alkyl group, or incorporation in a cyclic structure

More new derivatives have however continued to appear, with the UK reporting more novel cathinone derivatives detected in 2010 than any other country in Europe, with most of them first identified after the generic ban had gone into effect and thus already being illegal despite never having been previously reported.^[8]

In the United States, substituted cathinones are the psychoactive ingredients in "bath salts" which as of July 2011 were banned by at least 28 states, but not by the federal government.^[9]

See also

• Markush structure
• Substituted amphetamines
• Substituted methylenedioxyphenethylamines
• Substituted phenethylamines
• Substituted phenylmorpholines
• Arylcyclohexylamines

References

1. Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B. Khat use is associated with impaired working memory and cognitive flexibility. PLoS One. 2011;6(6):e20602. PMID 21698275. Retrieved 2011-07-17.
2. Advisory Council on the Misuse of Drugs (UK). Consideration of the cathinones. 31 March 2010. Retrieved 2011-07-17.
3. "The Misuse of Drugs (Amendment) (England, Wales and Scotland) Regulations 2010 No. 1144". Opsi.gov.uk. Retrieved 2010-04-08.
4. "NRG-1 'legal high' drug is banned". BBC News. 2010-07-12. Retrieved 2010-07-17.
5. "Advisory Council on the Misuse of Drugs Naphyrone Report (2010)". Home Office. 2010-07-07. Retrieved 2010-07-17.
6. "Explanatory Memorandum To The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799" (PDF). Opsi.gov.uk. Retrieved 2010-07-18.
7. "The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799" (PDF). Opsi.gov.uk. Retrieved 2010-07-18.
8. European Monitoring Centre on Drugs and Drug Addiction. EMCDDA–Europol 2010 Annual Report on the implementation of Council Decision 2005/387/JHA. Retrieved 2011-07-17.
9. Goodnough A, Zezima K. An Alarming New Stimulant, Legal in Many States. New York Times 2011 July 16. Retrieved 2011-07-17.