Substituted phenylmorpholines, or substituted phenmetrazines alternatively, are chemical derivatives of phenylmorpholine or of the psychostimulant drug phenmetrazine. Most such compounds act as releasers of monoamine neurotransmitters, and have stimulant effects. Some also act as agonists at serotonin receptors, and compounds with an N-propyl substitution act as dopamine receptor agonists. A number of derivatives from this class have been investigated for medical applications, such as for use as anorectics or medications for the treatment of ADHD. Some compounds have also become subject to illicit use as designer drugs.[1][2][3][4]

Various phenmetrazine derivatives
Various phenmetrazine derivatives
The 2S,3S isomer of phendimetrazine (i.e. (2S,3S)-3,4-dimethyl-2-phenylmorpholine)
The 2S,3S isomer of phendimetrazine (i.e. (2S,3S)-3,4-dimethyl-2-phenylmorpholine)
The (+)-enantiomer & (−)-enantiomer of pseudophenmetrazine.
The (+)-enantiomer & (−)-enantiomer of pseudophenmetrazine.
List of phenmetrazine analogues and related compounds
Substance Structure CAS number
2-phenylmorpholine
2-phenylmorpholine.svg
23972-41-0
2-phenyl-3-methylmorpholine (phenmetrazine)
Phenmetrazine.svg
134-49-6
2-phenyl-3,4-dimethylmorpholine (phendimetrazine)
Phendimetrazine.svg
634-03-7
2-phenyl-5-methylmorpholine (isophenmetrazine)
Isophenmetrazine structure.png
80123-66-6
2-phenyl-3-ethylmorpholine (phenetrazine)
Phenetrazine structure.png
100368-98-7
2-phenyl-3-methyl-4-ethylmorpholine (phenmetetrazine)
Phenmetetrazine structure.png
92196-09-3
2-phenyl-3,5-dimethylmorpholine (PDM-35)
2-phenyl-3,5-dimethylmorpholine.png
1218345-44-8
2-phenyl-3,6-dimethylmorpholine (6-methylphenmetrazine, 3,6-DMPM)
2-phenyl-3,6-dimethylmorpholine structure.png
92902-99-3
2-phenyl-5,5-dimethylmorpholine (G-130)
G-130 structure.png
42013-48-9
2-phenyl-3-methylmorpholin-5-one (fenmetramide)
Fenmetramide.png
5588-29-4
4-isopropyl-2-phenylmorpholine[5]
4-Isopropyl-2-phenylmorpholine.png
23222-62-0
Fenbutrazate
Fenbutrazate.png
4378-36-3
Morazone
Morazone.png
6536-18-1
2-Fluorophenmetrazine
2-Fluorophenmetrazine structure.png
1533654-24-8
3-fluorophenmetrazine (PAL-593)
3-fluorophenmetrazine proper structure.svg
1350768-28-3
4-Fluorophenmetrazine (PAL-748)
4-Fluorophenmetrazine structure.png
1097796-73-0
3-fluorophenetrazine
3-Fluorophenetrazine structure.png
3-chlorophenmetrazine (PAL-594)
3-Chlorophenmetrazine structure.png
1097796-78-5
3-Methoxyphenmetrazine
3-MeO-phenmetrazine structure.png
2-Methylphenmetrazine
2-Methylphenmetrazine structure.png
1507705-48-7
3-methylphenmetrazine (PAL-773)
3-Methylphenmetrazine structure.png
1350768-41-0
4-methylphenmetrazine (PAL-747)
4-Methylphenmetrazine structure.png
1998216-41-3
4-methylphendimetrazine
4-Methylphendimetrazine structure.png
1445576-23-7
3,4-Methylenedioxyphenmetrazine[6]
MDPHMZ structure.png
Naphthylmetrazine (PAL-704)
Naphthylmetrazine structure.png
2-(thiophen-2-yl)-3-methylmorpholine
2-Thiophenyl-3-methylmorpholine structure.png
2-(2,5-dimethoxy-4-bromophenyl)morpholine[7]
2CB-norphenmetrazine structure.png
2-(3-(Trifluoromethyl)phenyl)morpholine (flumexadol)[8]
Flumexadol structure.svg
30914-89-7
Oxaflozane
Oxaflozane.svg
26629-87-8
Phenmetrazol
Phenmetrazol structure.png
1350768-19-2
N-Ethylphenmetrazol
N-Ethylphenmetrazol structure.png
97630-98-3
(+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol (radafaxine)
Radafaxine Structural Formulae.png
106083-71-0
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethylmorpholin-2-ol (manifaxine)
GW-320,659 structure.png
135306-39-7
PF-219,061[9]
PF-219,061 Structural Formulae.png
710654-74-3
PF-592,379
PF-592379 structure.png
710655-15-5
OSU-6162
OSU-6162 structure.png
156907-84-5
2-Methyl-3-phenylpiperidine
2-Methyl-3-phenylpiperidine structure.png
70769-67-4
2-Phenyl-3-methyl-thiomorpholine
2-Phenyl-3-methyl-thiomorpholine structure.png
Picilorex
Picilorex.svg
62510-56-9
Butyltolylquinuclidine
Butyltolylquinuclidine structure.png
3-benzylmorpholine (3-BZM)[10]
3-benzylmorpholine.png
7684-27-7
3-Benzhydrylmorpholine (3-BZHM)
3-Benzhydrylmorpholine.svg
93406-27-0

See also

References

  1. ^ Boswell GE (1997). "Synthesis, stereochemistry and anti-tetrabenazine activity of bicyclo analogues of 2-phenylmorpholines". Journal of Heterocyclic Chemistry. 34 (6): 1813–1820. doi:10.1002/jhet.5570340629.
  2. ^ US 20130203752, Blough BE, Rothman R, Landavazo A, Page KM, Decker AM, "Phenylmorpholines and analogues thereof", published 8 August 2013 
  3. ^ Mayer FP, Burchardt NV, Decker AM, Partilla JS, Li Y, McLaughlin G, et al. (May 2018). "Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family". Neuropharmacology. 134 (Pt A): 149–157. doi:10.1016/j.neuropharm.2017.10.006. PMC 7294773. PMID 28988906.
  4. ^ McLaughlin G, Baumann MH, Kavanagh PV, Morris N, Power JD, Dowling G, et al. (September 2018). "Synthesis, analytical characterization, and monoamine transporter activity of the new psychoactive substance 4-methylphenmetrazine (4-MPM), with differentiation from its ortho- and meta- positional isomers". Drug Testing and Analysis. 10 (9): 1404–1416. doi:10.1002/dta.2396. PMC 7316143. PMID 29673128.
  5. ^ Chem-Sink (chemicals that are Sn2 products & Friedel-Crafts alkylation reactants)
  6. ^ Swist M, Wilamowski J, Zuba D, Kochana J, Parczewski A (May 2005). "Determination of synthesis route of 1-(3,4-methylenedioxyphenyl)-2-propanone (MDP-2-P) based on impurity profiles of MDMA". Forensic Science International. 149 (2–3): 181–92. doi:10.1016/j.forsciint.2004.06.016. PMID 15749360.
  7. ^ Glennon RA, Bondarev ML, Khorana N, Young R, May JA, Hellberg MR, et al. (November 2004). "Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane". Journal of Medicinal Chemistry. 47 (24): 6034–41. doi:10.1021/jm040082s. PMID 15537358.
  8. ^ Chemicalbook dot com: Flumexadol
  9. ^ Morpholine Dopamine Agonists For The Treatment Of Pain. Michael Andrew Ackley US 2009/0318451 AI Dec., 24th 2009. 1st Page.
  10. ^ NIH PubChem Compound Summary for CID 3283983