Dichloropane ((-)-2β-Carbomethoxy-3β-(3,4-dichlorophenyl)tropane, RTI-111, O-401) is a powerful SNDRI with IC50 (nM) values of 0.79, 3.13, and 18 at the DAT, SERT, and NET.[1]
Methylecgonidine as the direct precursor to this compound.[2]
In contrast to the closely related RTI-112, dichloropane is a potent stimulant drug which produces similar effects to cocaine in animal studies, although with a slower onset and longer duration of action.[3][4]
[edit] Transporter selectivity for disubstituted analogs
MAT IC50 (Ki) nM for 3',4'-Disubstituted Phenyltropanes.
| RTI |
P |
M |
[3H]WIN 35,428 |
[3H]Paroxetine |
[3H]Nisoxetine |
| 111 |
Cl |
Cl |
0.79 |
3.13 (0.29) |
18 (11) |
| 112 |
Cl |
Me |
0.82 ± 0.05 |
10.5 ± 0.41 (0.95 ± 0.04) |
36.2 ± 1.02 (21.8 ± 0.62) |
|
Cl |
Br |
0.42 ± 0.02 |
0.78 ± 0.04 (0.19 ± 0.01) |
7.24 ± 0.69 (3.62 ± 0.34) |
| Cl |
I |
0.41 ± 0.09 |
1.39 ± 0.23 (0.34 ± 0.06) |
15.1 ± 0.59 (7.74 ± 0.29) |
| Br |
Cl |
0.12 ± 0.04 |
0.94 ± 0.09 (0.23 ± 0.02) |
1.31 ± 0.13 (0.65 ± 0.07) |
| Br |
Br |
0.27 ± 0.01 |
0.71 ± 0.03 (0.18 ± 0.01) |
2.80 ± 0.16 (1.10 ± 0.08) |
| Br |
I |
0.21 ± 0.06 |
1.14 ± 0.26 (0.25 ± 0.04) |
10.4 ± 1.5 (5.12 ± 0.77) |
| I |
Cl |
0.26 ± 0.05 |
1.04 ± 0.14 (0.63 ± 0.05) |
1.26 ± 0.09 (0.63 ± 0.05) |
| I |
Br |
0.20 ± 0.04 |
0.58 ± 0.07 (0.14 ± 0.02) |
1.96 ± 0.17 (0.98 ± 0.09) |
| I |
I |
0.98 ± 0.05 |
2.0 ± 0.56 (0.19 ± 0.05) |
40.4 ± 3.56 (24 ± 2.1) |
| Me |
Me |
0.43 ± 0.07 |
9.88 ± 1.11 (2.42 ± 0.27) |
107 ± 11 (44 ± 4.7) |
DAT: (p-Br, m-Cl) < (p-I, m-Br) ≈ (p-Br, m-I) ~ (p-I, m-Cl) ≈ p,m-Br2 < (p-Cl, m-I) ≈ (p-Cl, m-Br) ≈ p,m-Me2 < p,m-Cl2 < (p-Cl, m-Me) < p,m-I2.
5HT: (p-I, m-Br) < p,m-Br2 ~ (p-Cl, m-Br) < (p-Br, m-Cl) ~ (p-I, m-Cl) < (p-Br, m-I) < (p-Cl, m-I) < p,m-I2 < p,m-Cl2 < (p-Cl, m-Me) < p,m-Me2.
NET: (p-I, m-Cl) ~ (p-Br, m-Cl) < (p-I, m-Br) < p,m-Br2 < (p-Cl, m-Br) < (p-Br, m-I) < (p-Cl, m-I) < p,m-Cl2 < (p-Cl, m-Me) < p,m-I2 < p,m-Me2.
[edit] See also
[edit] References
- ^ Carroll FI, Blough BE, Nie Z, Kuhar MJ, Howell LL, Navarro HA. Synthesis and Monoamine Transporter Binding Properties of 3-(3',4'-Disubstituted phenyl)tropane-2-carboxylic Acid Methyl Esters. J Med Chem. 2005 Apr 21;48(8):2767-71. PMID 15828814
- ^ Carroll FI, Mascarella SW, Kuzemko MA, Gao Y, Abraham P, Lewin AH, Boja JW, Kuhar MJ. Synthesis, ligand binding, and QSAR (CoMFA and classical) study of 3 beta-(3'-substituted phenyl)-, 3 beta-(4'-substituted phenyl)-, and 3 beta-(3',4'-disubstituted phenyl)tropane-2 beta-carboxylic acid methyl esters. Journal of Medicinal Chemistry. 1994 Sep 2;37(18):2865-73. PMID 8071935
- ^ Ranaldi R, Anderson KG, Carroll FI, Woolverton WL. Reinforcing and discriminative stimulus effects of RTI 111, a 3-phenyltropane analog, in rhesus monkeys: interaction with methamphetamine. Psychopharmacology (Berlin). 2000 Dec;153(1):103-10. PMID 11255920
- ^ Cook CD, Carroll IF, Beardsley PM. Cocaine-like discriminative stimulus effects of novel cocaine and 3-phenyltropane analogs in the rat. Psychopharmacology (Berlin). 2001 Dec;159(1):58-63. PMID 11797070
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| 2-Carboxymethyl Esters |
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| (3,4-Disubstituted Phenyl)-tropanes |
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| α,β Stereochemistry |
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| Heterocycles: 3-Substituted-isoxazol-5-yl |
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| Heterocycles: 3-Substituted-1,2,4-oxadiazole |
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| Irreversible |
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| Nortropanes (N-demethylated) |
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| Adamantanes |
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| Adenosine antagonists |
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| Arylcyclohexylamines |
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| Convulsants |
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| Eugeroics |
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| Oxazolines |
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| Phenethylamines |
1-(4-Methylphenyl)-2-aminobutane • 1-Phenyl-2-(piperidin-1-yl)pentan-3-one • 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane • 2-Fluoroamphetamine • 2-Fluoromethamphetamine • 2-OH-PEA • 2-Phenyl-3-aminobutane • 2-Phenyl-3-methylaminobutane • 2,3-MDA • 3-Fluoroamphetamine • 3-Fluoroethamphetamine • 3-Fluoromethcathinone • 3-Methoxyamphetamine • 3-Methylamphetamine • 3,4-DMMC • 4-BMC • 4-Ethylamphetamine • 4-FA • 4-FMA • 4-MA • 4-MMA • 4-MTA • 6-FNE • Alfetamine • α-Ethylphenethylamine • Amfecloral • Amfepentorex • Amfepramone • Amidephrine • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • Arbutamine • β-Methylphenethylamine • β-Phenylmethamphetamine • Benfluorex • Benzedrone • Benzphetamine • BDB (J) • BOH (Hydroxy-J) • BPAP • Buphedrone • Bupropion (Amfebutamone) • Butylone • Cathine • Cathinone • Chlorphentermine • Cinnamedrine • Clenbuterol • Clobenzorex • Cloforex • Clortermine • D-Deprenyl • Denopamine • Dimethoxyamphetamine • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, Metamfepramone) • Dobutamine • DOPA (Dextrodopa, Levodopa) • Dopamine • Dopexamine • Droxidopa • EBDB (Ethyl-J) • Ephedrine • Epinephrine (Adrenaline) • Epinine (Deoxyepinephrine) • Etafedrine • Ethcathinone (Ethylpropion) • Ethylamphetamine (Etilamfetamine) • Ethylnorepinephrine (Butanefrine) • Ethylone • Etilefrine • Famprofazone • Fenbutrazate • Fencamine • Fenethylline • Fenfluramine (Dexfenfluramine) • Fenmetramide • Fenproporex • Flephedrone • Fludorex • Furfenorex • Gepefrine • HMMA • Hordenine • Ibopamine • IMP • Indanylamphetamine • Isoetarine • Isoethcathinone • Isoprenaline (Isoproterenol) • L-Deprenyl (Selegiline) • Lefetamine • Lisdexamfetamine • Lophophine (Homomyristicylamine) • Manifaxine • MBDB (Methyl-J; "Eden") • MDA (Tenamfetamine) • MDBU • MDEA ("Eve") • MDMA ("Ecstasy", "Adam") • MDMPEA (Homarylamine) • MDOH • MDPR • MDPEA (Homopiperonylamine) • Mefenorex • Mephedrone • Mephentermine • Metanephrine • Metaraminol • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methoxamine • Methoxyphenamine • MMA • Methcathinone (Methylpropion) • Methedrone • Methoxyphenamine • Methylone • MMDA • MMDMA • MMMA • Morazone • N-Benzyl-1-phenethylamine • N,N-Dimethylphenethylamine • Naphthylamphetamine • Nisoxetine • Norepinephrine (Noradrenaline) • Norfenefrine • Norfenfluramine • Normetanephrine • Octopamine • Orciprenaline • Ortetamine • Oxilofrine • Paredrine (Norpholedrine, Oxamphetamine, Mycadrine) • PBA • PCA • PHA • Pargyline • Pentorex (Phenpentermine) • Pentylone • Phenatine • Phendimetrazine • Phenmetrazine • Phenpromethamine • Phentermine • Phenylalanine • Phenylephrine (Neosynephrine) • Phenylpropanolamine • Pholedrine • PIA • PMA • PMEA • PMMA • PPAP • Prenylamine • Propylamphetamine • Pseudoephedrine • Radafaxine • Ropinirole • Salbutamol (Albuterol; Levosalbutamol) • Sibutramine • Synephrine (Oxedrine) • Theodrenaline • Tiflorex (Flutiorex) • Tranylcypromine • Tyramine • Tyrosine • Xamoterol • Xylopropamine • Zylofuramine
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| Piperidines |
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| Pyrrolidines |
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| Tropanes |
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- Adamantanes: Amantadine
- Memantine
- Rimantadine; Aminotetralins: 7-OH-DPAT
- 8-OH-PBZI
- Rotigotine
- UH-232; Benzazepines: 6-Br-APB
- Fenoldopam
- SKF-38,393
- SKF-77,434
- SKF-81,297
- SKF-82,958
- SKF-83,959; Ergolines: Bromocriptine
- Cabergoline
- Dihydroergocryptine
- Lisuride
- LSD
- Pergolide; Dihydrexidine derivatives: 2-OH-NPA
- A-86,929
- Ciladopa
- Dihydrexidine
- Dinapsoline
- Dinoxyline
- Doxanthrine; Others: A-68,930
- A-77636
- A-412,997
- ABT-670
- ABT-724
- Aplindore
- Apomorphine
- Aripiprazole
- Bifeprunox
- BP-897
- CY-208,243
- Dizocilpine
- Etilevodopa
- Flibanserin
- Ketamine
- Melevodopa
- Modafinil
- Pardoprunox
- Phencyclidine
- PD-128,907
- PD-168,077
- PF-219,061
- Piribedil
- Pramipexole
- Propylnorapomorphine
- Pukateine
- Quinagolide
- Quinelorane
- Quinpirole
- RDS-127
- Ro10-5824
- Ropinirole
- Rotigotine
- Roxindole
- Salvinorin A
- SKF-89,145
- Sumanirole
- Terguride
- Umespirone
- WAY-100,635
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- Morpholines: Fenbutrazate
- Morazone
- Phendimetrazine
- Phenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX)
- Aminorex
- Clominorex
- Cyclazodone
- Fenozolone
- Fluminorex
- Pemoline
- Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA)
- 4-CAB
- 4-Methylamphetamine (4-MA)
- 4-Methylmethamphetamine (4-MMA)
- Alfetamine
- Amfecloral
- Amfepentorex
- Amfepramone
- Amphetamine (Dextroamphetamine
- Levoamphetamine)
- Amphetaminil
- β-Methylphenethylamine (β-Me-PEA)
- Benzodioxolylbutanamine (BDB)
- Benzodioxolylhydroxybutanamine (BOH)
- Benzphetamine
- Buphedrone
- Butylone
- Cathine
- Cathinone
- Clobenzorex
- Clortermine
- D-Deprenyl
- Dimethoxyamphetamine (DMA)
- Dimethoxymethamphetamine (DMMA)
- Dimethylamphetamine
- Dimethylcathinone (Dimethylpropion, metamfepramone)
- Ethcathinone (Ethylpropion)
- Ethylamphetamine
- Ethylbenzodioxolylbutanamine (EBDB)
- Ethylone
- Famprofazone
- Fenethylline
- Fenproporex
- Flephedrone
- Fludorex
- Furfenorex
- Hordenine
- Lophophine (Homomyristicylamine)
- Mefenorex
- Mephedrone
- Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine
- Levomethamphetamine)
- Methcathinone (Methylpropion)
- Methedrone
- Methoxymethylenedioxyamphetamine (MMDA)
- Methoxymethylenedioxymethamphetamine (MMDMA)
- Methylbenzodioxolylbutanamine (MBDB)
- Methylenedioxyamphetamine (MDA, tenamfetamine)
- Methylenedioxyethylamphetamine (MDEA)
- Methylenedioxyhydroxyamphetamine (MDOH)
- Methylenedioxymethamphetamine (MDMA)
- Methylenedioxymethylphenethylamine (MDMPEA, homarylamine)
- Methylenedioxyphenethylamine (MDPEA, homopiperonylamine)
- Methylone
- Ortetamine
- Parabromoamphetamine (PBA)
- Parachloroamphetamine (PCA)
- Parafluoroamphetamine (PFA)
- Parafluoromethamphetamine (PFMA)
- Parahydroxyamphetamine (PHA)
- Paraiodoamphetamine (PIA)
- Paredrine (Norpholedrine, Oxamphetamine)
- Phenethylamine (PEA)
- Pholedrine
- Phenpromethamine
- Prenylamine
- Propylamphetamine
- Tiflorex (Flutiorex)
- Tyramine (TRA)
- Xylopropamine
- Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP)
- Benzylpiperazine (BZP)
- Methoxyphenylpiperazine (MeOPP, paraperazine)
- Methylbenzylpiperazine (MBZP)
- Methylenedioxybenzylpiperazine (MDBZP, piperonylpiperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN)
- 2-Aminoindane (2-AI)
- 2-Aminotetralin (2-AT)
- 4-Benzylpiperidine (4-BP)
- 5-IAI
- Clofenciclan
- Cyclopentamine
- Cypenamine
- Cyprodenate
- Feprosidnine
- Gilutensin
- Heptaminol
- Hexacyclonate
- Indanylaminopropane (IAP)
- Indanorex
- Isometheptene
- Methylhexanamine
- Naphthylaminopropane (NAP)
- Octodrine
- Phthalimidopropiophenone
- Propylhexedrine (Levopropylhexedrine)
- Tuaminoheptane (Tuamine)
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