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
The 2S,3S isomer of phendimetrazine (
i.e. (2S,3S)-3,4-dimethyl-2-phenylmorpholine)
The (+)-enantiomer & (−)-enantiomer of
pseudophenmetrazine .
List of phenmetrazine analogues and related compounds
Substance
Structure
CAS number
2-phenylmorpholine
23972-41-0
2-phenyl-3-methylmorpholine (phenmetrazine)
134-49-6
2-phenyl-3,4-dimethylmorpholine (phendimetrazine )
634-03-7
2-phenyl-5-methylmorpholine (isophenmetrazine)
80123-66-6
2-phenyl-3-ethylmorpholine (phenetrazine)
100368-98-7
2-phenyl-3-methyl-4-ethylmorpholine (phenmetetrazine)
92196-09-3
2-phenyl-3,5-dimethylmorpholine (PDM-35 )
1218345-44-8
2-phenyl-3,6-dimethylmorpholine (6-methylphenmetrazine, 3,6-DMPM)
92902-99-3
2-phenyl-5,5-dimethylmorpholine (G-130 )
42013-48-9
2-phenyl-3-methylmorpholin-5-one (fenmetramide )
5588-29-4
4-isopropyl-2-phenylmorpholine[5]
23222-62-0
Fenbutrazate
4378-36-3
Morazone
6536-18-1
2-Fluorophenmetrazine
1533654-24-8
3-fluorophenmetrazine (PAL-593)
1350768-28-3
4-Fluorophenmetrazine (PAL-748)
1097796-73-0
3-chlorophenmetrazine (PAL-594)
1097796-78-5
3-Methoxyphenmetrazine
2-Methylphenmetrazine
1507705-48-7
(PAL-773)
1350768-41-0
4-methylphenmetrazine (PAL-747)
1998216-41-3
1445576-23-7
3,4-Methylenedioxyphenmetrazine [6]
Naphthylmetrazine (PAL-704)
2-(thiophen-2-yl)-3-methylmorpholine
2-(2,5-dimethoxy-4-bromophenyl)morpholine[7]
2-(3-(Trifluoromethyl)phenyl)morpholine (flumexadol )[8]
30914-89-7
Oxaflozane
26629-87-8
Phenmetrazol
1350768-19-2
N-Ethylphenmetrazol
97630-98-3
(+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol (radafaxine )
106083-71-0
(2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethylmorpholin-2-ol (manifaxine )
135306-39-7
PF-219,061 [9]
710654-74-3
PF-592,379
710655-15-5
OSU-6162
156907-84-5
2-Methyl-3-phenylpiperidine
70769-67-4
2-Phenyl-3-methyl-thiomorpholine
Picilorex
62510-56-9
Butyltolylquinuclidine
(3-BZM)[10]
7684-27-7
3-Benzhydrylmorpholine (3-BZHM)
93406-27-0
See also [ ]
Substituted amphetamine
Substituted benzofuran
Substituted cathinone
Substituted methylenedioxyphenethylamine
List of aminorex analogues
List of methylphenidate analogues
List of phenyltropanes
List of cocaine analogues
References [ ]
^ 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 .
^ US 20130203752 , Blough BE, Rothman R, Landavazo A, Page KM, Decker AM, "Phenylmorpholines and analogues thereof", published 8 August 2013
^ 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 .
^ 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 .
^ Chem-Sink (chemicals that are Sn2 products & Friedel-Crafts alkylation reactants)
^ 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 .
^ 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 .
^ Chemicalbook dot com: Flumexadol
^ Morpholine Dopamine Agonists For The Treatment Of Pain. Michael Andrew Ackley US 2009/0318451 AI Dec., 24th 2009. 1st Page.
^ NIH PubChem Compound Summary for CID 3283983
External links [ ]
Antiobesity agents /Anorectics (A08 )
Central
Stimulants
4-Methylamphetamine ‡
Amfecloral
Amfepentorex
Amfepramone
Aminorex ‡
Amphetamine
Amphetaminil
Atomoxetine
Benfluorex ‡
Benzphetamine
Bupropion (+naltrexone ; +zonisamide† )
Cathine
Cathinone
Chlorphentermine
Ciclazindol
Clobenzorex
Cloforex
Clominorex
Clortermine
Dexfenfluramine ‡
Dextroamphetamine
Dexmethylphenidate
Difemetorex ‡
Dimethylcathinone
Ephedrine
Ephedra ‡
Etilamfetamine
Etolorex
Fenbutrazate
Fencamfamin
Fenethylline
Fenfluramine (+phentermine ‡ )
Fenproporex
Fludorex
Fluminorex
Furfenorex ‡
Indanorex
Khat
Levopropylhexedrine
Lisdexamfetamine
Manifaxine
Mazindol
Mefenorex
Methamphetamine
Methylphenidate
Norfenfluramine
Pemoline
Pentorex
Phendimetrazine
Phenethylamine
Phenmetrazine
Phentermine (+topiramate )
Phenylpropanolamine
Picilorex
Pipradrol
Prolintane
Propylhexedrine
Pseudoephedrine
Pyrovalerone
Radafaxine
Reboxetine
Setazindol
Sibutramine ‡
Synephrine
Tesofensine
Viloxazine
Xylopropamine
Zylofuramine
Cannabinoid receptor antagonists Others
5-HTP
Beloranib §
Galactomannan
Glucomannan
L-DOPA
L-Phenylalanine
L-Tryptophan
L-Tyrosine
Lorcaserin
Lu AA-33810
Metformin
Naltrexone
Naloxone
Oxyntomodulin
P57
Peptide YY
Setmelanotide
Topiramate
Velneperit §
Yohimbine (Yohimbe )
Zonisamide
Water
Peripheral
# WHO-EM
‡ Withdrawn from market
Clinical trials :
† Phase III
§ Never to phase III
α1
Agonists
6-FNE
Amidephrine
Buspirone
Cirazoline
Corbadrine
Deoxyepinephrine (epinine, N -methyldopamine)
Dipivefrine
Dopamine
Droxidopa (L -DOPS)
Epinephrine
Etilefrine
Etilevodopa
Ethylnorepinephrine
Ibopamine
Indanidine
Isometheptene
L -DOPA (levodopa)
L -Phenylalanine
L -Tyrosine
Melevodopa
Metaraminol
Methoxamine
Methyldopa
Midodrine
Naphazoline
Norepinephrine
Octopamine
Oxymetazoline
Phenylephrine
Phenylpropanolamine
Synephrine
Tetryzoline
Tiamenidine
Xylometazoline
Antagonists
Abanoquil
Ajmalicine
Alfuzosin
Anisodamine
Anisodine
Atiprosin
Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone )
Benoxathian
Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol )
Buflomedil
Bunazosin
Corynanthine
Dapiprazole
Domesticine
Doxazosin
Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride )
Etoperidone
Fenspiride
Hydroxyzine
Indoramin
Ketanserin
L-765,314
mCPP
Mepiprazole
Metazosin
Monatepil
Moxisylyte
Naftopidil
Nantenine
Neldazosin
Niaprazine
Niguldipine
Pardoprunox
Pelanserin
Perlapine
Phendioxan
Phenoxybenzamine
Phentolamine
Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )
Piperoxan
Prazosin
Quinazosin
Quinidine
Silodosin
Spegatrine
Spiperone
Talipexole
Tamsulosin
Terazosin
Tiodazosin
Tolazoline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine )
Trimazosin
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Urapidil
WB-4101
Zolertine
α2
Agonists
(R)-3-Nitrobiphenyline
4-NEMD
6-FNE
Amitraz
Apraclonidine
Brimonidine
Clonidine
Corbadrine
Deoxyepinephrine (epinine, N -methyldopamine)
Detomidine
Dexmedetomidine
Dihydroergotamine
Dipivefrine
Dopamine
Droxidopa (L -DOPS)
Etilevodopa
Ergotamine
Epinephrine
Etilefrine
Ethylnorepinephrine
Guanabenz
Guanfacine
Guanoxabenz
L -DOPA (levodopa)
L -Phenylalanine
L -Tyrosine
Ibopamine
Lofexidine
Medetomidine
Melevodopa
Methyldopa
Mivazerol
Moxonidine
Naphazoline
Norepinephrine
Oxymetazoline
Phenylpropanolamine
Piperoxan
Rilmenidine
Romifidine
Talipexole
Tetrahydrozoline
Tiamenidine
Tizanidine
Tolonidine
Urapidil
Xylazine
Xylometazoline
Antagonists
1-PP
Adimolol
Amesergide
Aptazapine
Atipamezole
Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine )
Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone )
BRL-44408
Buflomedil
Cirazoline
Efaroxan
Esmirtazapine
Fenmetozole
Fluparoxan
Idazoxan
Ketanserin
Lisuride
mCPP
Mianserin
Mirtazapine
NAN-190
Pardoprunox
Phentolamine
Phenoxybenzamine
Piperoxan
Piribedil
Rauwolscine
Rotigotine
Setiptiline
Spegatrine
Spiroxatrine
Sunepitron
Terguride
Tolazoline
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Yohimbine
β
Agonists
Abediterol
Alifedrine
Amibegron
Arbutamine
Arformoterol
Arotinolol
BAAM
Bambuterol
Befunolol
Bitolterol
Broxaterol
Buphenine
Carbuterol
Carmoterol
Cimaterol
Clenbuterol
Colterol
Corbadrine
Denopamine
Deoxyepinephrine (epinine, N -methyldopamine)
Dipivefrine
Dobutamine
Dopamine
Dopexamine
Droxidopa (L -DOPS)
Epinephrine
Etafedrine
Etilefrine
Etilevodopa
Ethylnorepinephrine
Eugenodilol
Fenoterol
Formoterol
Hexoprenaline
Higenamine
Ibopamine
Indacaterol
Isoetarine
Isoprenaline
Isoxsuprine
L -DOPA (levodopa)
L -Phenylalanine
L -Tyrosine
Levosalbutamol
Lubabegron
Mabuterol
Melevodopa
Methoxyphenamine
Methyldopa
Mirabegron
Norepinephrine
Orciprenaline
Oxyfedrine
PF-610355
Phenylpropanolamine
Pirbuterol
Prenalterol
Ractopamine
Procaterol
Reproterol
Rimiterol
Ritodrine
Salbutamol
Salmeterol
Solabegron
Terbutaline
Tretoquinol
Tulobuterol
Vibegron
Vilanterol
Xamoterol
Zilpaterol
Zinterol
Antagonists
See also: Receptor/signaling modulators
Dopaminergics
Serotonergics
Monoamine reuptake inhibitors
Monoamine releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins
D1 -like
Agonists
Benzazepines : 6-Br-APB
Fenoldopam
SKF-38,393
SKF-77,434
SKF-81,297
SKF-82,958
SKF-83,959
Trepipam
Ergolines : Cabergoline
CY-208,243
Dihydroergocryptine
Lisuride
Pergolide
Terguride
Dihydrexidine derivatives : A-77636
A-86929
Adrogolide (ABT-431, DAS-431)
Dihydrexidine
Dinapsoline
Dinoxyline
Doxanthrine
Phenethylamines :
Deoxyepinephrine (N-methyldopamine, epinine)
Dopexamine
Etilevodopa
Ibopamine
L -DOPA (levodopa)
Melevodopa
L -Phenylalanine
L -Tyrosine
Others : A-68930
Apomorphine
Nuciferine
PF-6649751
Propylnorapomorphine
Rotigotine
SKF-89,145
Stepholidine
Tavapadon
Tetrahydropalmatine
PAMs Antagonists
Typical antipsychotics : Butaclamol
Chlorpromazine
Chlorprothixene
Flupentixol (flupenthixol) (+melitracen )
Fluphenazine
Loxapine
Perphenazine (+amitriptyline )
Thioridazine
Thiothixene
Trifluoperazine (+tranylcypromine )
Zuclopenthixol
Atypical antipsychotics : Asenapine
Clorotepine
Clotiapine
Clozapine
DHA-clozapine
Fluperlapine
Iloperidone
Norclozapine
Olanzapine (+fluoxetine )
Paliperidone
Quetiapine
Risperidone
Zicronapine
Ziprasidone
Zotepine
Others :
Ecopipam
EEDQ
Metitepine (methiothepin)
Perlapine
SCH-23390
D2 -like
Agonists
Adamantanes : Amantadine
Memantine
Rimantadine
Aminotetralins : 5-OH-DPAT
7-OH-DPAT
8-OH-PBZI
Rotigotine
UH-232
Ergolines : Bromocriptine
Cabergoline
Chanoclavine
Dihydroergocryptine
Epicriptine
Ergocornine
Lergotrile
Lisuride
LSD
Pergolide
Terguride
Phenethylamines : Deoxyepinephrine (N-methyldopamine, epinine)
Dopexamine
Etilevodopa
Ibopamine
L -DOPA (levodopa)
L -Phenylalanine
L -Tyrosine
Melevodopa
Atypical antipsychotics : Alentemol (U-66444B)
Aripiprazole (+sertraline )
Aripiprazole lauroxil
Bifeprunox
Brexpiprazole
Brilaroxazine
Cariprazine
F-15063
Lumateperone
Norclozapine
Others : 3-PPP
A-412997
ABT-670
ABT-724
Adrafinil
Aplindore
Apomorphine
Arketamine
Armodafinil
BP-897
Captodiame
CP-226,269
Dizocilpine
Esketamine
Flibanserin
Ketamine
Mesulergine
Modafinil
OSU-6162
Pardoprunox
PD-128,907
PD-168,077
PF-219,061
PF-592,379
Phencyclidine
Piribedil
Pramipexole
Preclamol
Propylnorapomorphine
Pukateine
Quinagolide
Quinelorane
Quinpirole
RDS-127
Ro10-5824
Ropinirole
Roxindole
Salvinorin A
SKF-83,959
Sumanirole
Talipexole
Umespirone
WAY-100,635
Antagonists
See also: Receptor/signaling modulators
Adrenergics
Serotonergics
Monoamine reuptake inhibitors
Monoamine releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins