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{{Short description|Chemical compound}} |
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{{Drugbox| |
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{{Infobox drug |
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|IUPAC_name = methyl (1R,2S,3S,5S)-3-(4-fluorophenyl)-8-methyl- 8-azabicyclooctane-2-carboxylate |
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| image = WIN 35428 structural formula.png |
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| CAS_number= 50370-56-4 |
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| verifiedrevid = 413466418 |
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| CAS_supplemental = <br>77210-32-3 |
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| IUPAC_name = Methyl (1''R'',2''S'',3''S'',5''S'')-3-(4-fluorophenyl)-8-methyl-8-azabicyclooctane-2-carboxylate |
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| image = Phenyltropane 11b - WIN 35428.svg |
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| ATC_suffix= |
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<!--Clinical data-->| tradename = |
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| PubChem= 105056 |
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| legal_US = Schedule II |
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| DrugBank= |
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| legal_status = <!--Identifiers--> |
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| chemical_formula = C<sub>16</sub>H<sub>20</sub>FNO<sub>2</sub>·C<sub>10</sub>H<sub>8</sub>S<sub>2</sub>O<sub>6</sub> |
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| C=16 | H=20 | F=1 | N=1 | O=2 |
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| IUPHAR_ligand = 4606 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| molecular_weight = 277.33 g/mol (free base); 565.55 (anhydrous naphthalenedisulfonate) |
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| CAS_number = 50370-56-4 |
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| smiles = CN12CC1((C2)C3=CC=C(C=C3)F)C(=O)OC |
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| CAS_supplemental = <br>77210-32-3 |
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| synonyms = CFT, WIN 35,428 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| melting_point = 202 |
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| melting_high = 204 |
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| UNII = 8ZT6KJ947T |
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| PubChem = 105056 |
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| specific_rotation = -62.5° |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| bioavailability= |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| metabolism = |
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| ChEMBL = 541252 |
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| elimination_half-life= |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| excretion = |
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| ChemSpiderID = 94788 |
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| pregnancy_category = |
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<!--Chemical data--> |
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| legal_status = Schedule II (US) |
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| C = 16 |
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| routes_of_administration= |
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| H = 20 |
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| F = 1 |
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| N = 1 |
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| O = 2 |
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| SMILES = CN12CC1((C2)C3=CC=C(C=C3)F)C(=O)OC |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C16H20FNO2/c1-18-12-7-8-14(18)15(16(19)20-2)13(9-12)10-3-5-11(17)6-4-10/h3-6,12-15H,7-9H2,1-2H3/t12-,13+,14+,15-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = QUSLQENMLDRCTO-YJNKXOJESA-N |
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| synonyms = CFT, WIN 35,428 |
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| melting_point = 202 |
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| melting_high = 204 |
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| specific_rotation = -62.5° |
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'''(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane''' ('''β-CFT''', '''WIN 35,428''') is a ], drug used in scientific research. CFT is a ] based ] and is structurally derived from ]. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While the ] salt is the most commonly used form in scientific research due to its high ] in water, the free base and ] salts are known compounds and can also be produced. The tartrate is another salt form that is reported.<ref name=Wee>{{cite journal | last1 = Wee | first1 = S | last2 = Carroll | first2 = FI | last3 = Woolverton | first3 = WL | title = A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants | url = http://www.nature.com/npp/journal/v31/n2/full/1300795a.html | journal = Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology | volume = 31 | issue = 2 | pages = 351–62 | year = 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 }}</ref> |
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'''WIN 35,428''' ('''β-CFT''', '''(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane''') is a ] drug used in scientific research. CFT is a ] based ] and is structurally derived from ]. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While the ] salt is the most commonly used form in scientific research due to its high ] in water, the free base and ] salts are known compounds and can also be produced. The tartrate is another salt form that is reported.<ref name=Wee>{{cite journal | vauthors = Wee S, Carroll FI, Woolverton WL | title = A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants | journal = Neuropsychopharmacology | volume = 31 | issue = 2 | pages = 351–362 | date = February 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 | doi-access = free }}</ref> |
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== Uses == |
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== Uses == |
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CFT was first reported by Clarke and co-workers in 1973.<ref name=Clarke>{{cite journal | last1 = Clarke | first1 = RL | last2 = Daum | first2 = SJ | last3 = Gambino | first3 = AJ | last4 = Aceto | first4 = MD | last5 = Pearl | first5 = J | last6 = Levitt | first6 = M | last7 = Cumiskey | first7 = WR | last8 = Bogado | first8 = EF | title = Compounds affecting the central nervous system. 4. 3 Beta-phenyltropane-2-carboxylic esters and analogs | journal = Journal of medicinal chemistry | volume = 16 | issue = 11 | pages = 1260–7 | year = 1973 | pmid = 4747968 | doi=10.1021/jm00269a600}}</ref> This drug is known to function as a "positive reinforcer" (although it is less likely to be self-administered by rhesus monkeys than cocaine).<ref name=Wee/> Tritiated CFT is frequently used to map binding of novel ligands to the ], although the drug also has some ] affinity. |
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CFT was first reported by Clarke and co-workers in 1973.<ref name=Clarke>{{cite journal | vauthors = Clarke RL, Daum SJ, Gambino AJ, Aceto MD, Pearl J, Levitt M, Cumiskey WR, Bogado EF | display-authors = 6 | title = Compounds affecting the central nervous system. 4. 3 Beta-phenyltropane-2-carboxylic esters and analogs | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 11 | pages = 1260–1267 | date = November 1973 | pmid = 4747968 | doi = 10.1021/jm00269a600 | s2cid = 8105834 }}</ref> This drug is known to function as a "positive reinforcer" (although it is less likely to be self-administered by rhesus monkeys than cocaine).<ref name=Wee/> Tritiated CFT is frequently used to map binding of novel ligands to the ], although the drug also has some ] affinity. |
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] forms of CFT have been used in humans and animals to map the distribution of ] transporters in the ]. CFT was found to be particularly useful for this application as a normal fluorine atom can be substituted with the radioactive isotope ] which is widely used in ]. Another radioisotope-substituted ] WIN 35,428 (where the carbon atom of either the N-methyl group, or the ] from the 2-carbomethoxy group of CFT, has been replaced with <sup>11</sup>C) is now more commonly used for this application, as it is quicker and easier in practice to make radiolabelled CFT by methylating nor-CFT or 2-desmethyl-CFT than by reacting ] with parafluorophenylmagnesium bromide, and also avoids the requirement for a licence to work with the restricted precursor ]. |
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] forms of CFT have been used in humans and animals to map the distribution of ] transporters in the ]. CFT was found to be particularly useful for this application as a normal fluorine atom can be substituted with the radioactive isotope ] which is widely used in ]. Another radioisotope-substituted ] WIN 35,428 (where the carbon atom of either the N-methyl group, or the ] from the 2-carbomethoxy group of CFT, has been replaced with <sup>11</sup>C) is now more commonly used for this application, as it is quicker and easier in practice to make radiolabelled CFT by methylating nor-CFT or 2-desmethyl-CFT than by reacting ] with parafluorophenylmagnesium bromide, and also avoids the requirement for a licence to work with the restricted precursor ]. |
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CFT is about as addictive as cocaine in animal studies, but is taken less often due to its longer duration of action. Potentially this could make it a suitable drug to be used as a substitute for ], in a similar manner to how ] is used as a substitute for ]s in treating addiction. |
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CFT is about as addictive as cocaine in animal studies, but is taken less often due to its longer duration of action. Potentially this could make it a suitable drug to be used as a substitute for ], in a similar manner to how ] is used as a substitute for ]s in treating addiction. |
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== Street Drug == |
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== Street drug == |
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In August 2010, some media sources claimed that the ], ] contained WIN 35,428.<ref name="Metro.co.uk">{{cite web|url=http://www.metro.co.uk/news/838315-ivory-wave-the-new-meow-meow |title=Ivory Wave: The new meow meow? |publisher=Metro.co.uk |date=2010-08-17 |accessdate=2010-08-23}}</ref> However, samples of Ivory Wave have been found to contain ],<ref>{{cite news|author=Sam Jones and Mike Power |url=http://www.guardian.co.uk/society/2010/aug/17/ivory-wave-drug-alleged-death |title=Ivory Wave drug implicated in death of 24-year-old man | Society | guardian.co.uk |publisher=Guardian |date= 2010-08-17|accessdate=2010-08-23 | location=London}}</ref> so the legitimacy of these claims remains unclear. |
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In August 2010, some media sources claimed that the ] ] contained WIN 35428.<ref name="Metro.co.uk">{{cite web|url=http://www.metro.co.uk/news/838315-ivory-wave-the-new-meow-meow |title=Ivory Wave: The new meow meow? |publisher=Metro.co.uk |date=2010-08-17 |access-date=2010-08-23}}</ref> However, samples of Ivory Wave have been found to contain ],<ref>{{cite news| vauthors = Jones S, Power M |url= https://www.theguardian.com/society/2010/aug/17/ivory-wave-drug-alleged-death |title=Ivory Wave drug implicated in death of 24-year-old man | Society | guardian.co.uk |publisher=Guardian |date= 2010-08-17|access-date=2010-08-23 | location=London}}</ref> so the legitimacy of these claims remains unclear. |
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== Legal Status == |
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== Legal status == |
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CFT is not specifically scheduled in the United States,<ref>{{cite web |url=https://www.justice.gov/dea/pubs/scheduling.html |title=DEA, Drug Scheduling |access-date=2011-04-07 |archive-date=2013-06-29 |archive-url=https://web.archive.org/web/20130629153729/http://www.justice.gov/dea/pubs/scheduling.html |url-status=dead }}</ref> though it meets the statutory definition of an ecgonine derivative. Consequently, it is a Schedule II drug.<ref>{{Cite web |title=21 USC 812: Schedules of controlled substances |url=https://uscode.house.gov/view.xhtml?req=38&f=treesort&num=5465 |access-date=2023-07-18 |website=uscode.house.gov}}</ref> |
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CFT is illegal in the ] (Schedule II)<ref>{{cite web|url=http://www.visn20.med.va.gov/portland/research/pdf-documents/csi_research_policy.pdf |title=Controlled Substances in Research Policy (Portland VA Medical Center) |format=PDF |date= |accessdate=2010-08-23}}</ref><ref name="sigma">{{cite web|url=http://www.sigmaaldrich.com/catalog/search/ProductDetail?ProdNo=C124&Brand=SIGMA |title=C124 β-CFT naphthalenedisulfonate monohydrate solid |publisher=Sigmaaldrich.com |date= |accessdate=2010-08-23}}</ref> and ] (Kontrollierte Droge).<ref name="sigma"/> Its legal status in other countries is unclear. |
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== Toxicity == |
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== Toxicity == |
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Administering 100 mg/kg of CFT to rats only resulted in convulsions being reported, whereas ] had the ability to cause death at this dose.<ref name=Navarro>{{cite journal | last1 = Carroll | first1 = FI | last2 = Runyon | first2 = SP | last3 = Abraham | first3 = P | last4 = Navarro | first4 = H | last5 = Kuhar | first5 = MJ | last6 = Pollard | first6 = GT | last7 = Howard | first7 = JL | title = Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers | journal = Journal of medicinal chemistry | volume = 47 | issue = 25 | pages = 6401–9 | year = 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 }}</ref> |
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Administering 100 mg/kg of CFT to rats only resulted in convulsions being reported, whereas ] had the ability to cause death at this dose.<ref name=Navarro>{{cite journal | vauthors = Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL | title = Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 25 | pages = 6401–6409 | date = December 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 | s2cid = 26612669 }}</ref> |
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==See also== |
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== See also == |
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==References== |
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== References == |
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{{Reflist}} |
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{{Reflist}} |
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== Further reading == |
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==References== |
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{{refbegin|30em}} |
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*D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP. Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428). ''Neuropharmacology''. 1979 Dec;18(12):1009-10. |
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* {{cite journal | vauthors = D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP | title = Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428) | journal = Neuropharmacology | volume = 18 | issue = 12 | pages = 1009–1010 | date = December 1979 | pmid = 530372 | doi = 10.1016/0028-3908(79)90167-9 | s2cid = 31564203 }} |
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*Reith, MEA., Sershen H, Lajtha A. Saturable (3H)cocaine binding in central nervous system of mouse. ''Life Sciences''. 1980 Sep 22;27(12):1055-62. |
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* {{cite journal | vauthors = Reith ME, Sershen H, Lajtha A | title = Saturable (3H)cocaine binding in central nervous system of mouse | journal = Life Sciences | volume = 27 | issue = 12 | pages = 1055–1062 | date = September 1980 | pmid = 6106874 | doi = 10.1016/0024-3205(80)90029-6 }} |
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*Spealman RD, Bergman J, Madras BK. Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane. ''Pharmacology Biochemistry and Behaviour''. 1991 Aug;39(4):1011-3. |
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* {{cite journal | vauthors = Spealman RD, Bergman J, Madras BK | title = Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane | journal = Pharmacology, Biochemistry, and Behavior | volume = 39 | issue = 4 | pages = 1011–1013 | date = August 1991 | pmid = 1763097 | doi = 10.1016/0091-3057(91)90067-c | s2cid = 53272758 }} |
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*Milius RA, Saha JK, Madras BK, Neumeyer JL. Synthesis and Receptor Binding of N-Substituted Tropane Derivatives. High- Affinity Ligands for the Cocaine Receptor. ''Journal of Medicinal Chemistry''. 1991,34, 1728–1731 |
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* {{cite journal | vauthors = Milius RA, Saha JK, Madras BK, Neumeyer JL | title = Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 5 | pages = 1728–1731 | date = May 1991 | pmid = 2033595 | doi = 10.1021/jm00109a029 | s2cid = 22777518 }} |
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*Cline EJ, Scheffel U, Boja JW, Carroll FI, Katz JL, Kuhar MJ. Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency. ''Journal of Pharmacology and Experimental Therapeutics''. 1992 Mar;260(3):1174-9. |
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* {{cite journal | vauthors = Cline EJ, Scheffel U, Boja JW, Carroll FI, Katz JL, Kuhar MJ | title = Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 3 | pages = 1174–1179 | date = March 1992 | pmid = 1545384 }} |
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*Singh S. Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. ''Chemistry Reviews'', 2000. 100(3): 925-1024 |
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* {{cite journal | vauthors = Singh S | title = Chemistry, design, and structure-activity relationship of cocaine antagonists | journal = Chemical Reviews | volume = 100 | issue = 3 | pages = 925–1024 | date = March 2000 | pmid = 11749256 | doi = 10.1021/cr9700538 | s2cid = 36764655 }} |
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*Li SM, Campbell BL, Katz JL. Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine. ''Journal of Pharmacology and Experimental Therapeutics''. 2006 Jun;317(3):1088-96. |
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* {{cite journal | vauthors = Li SM, Campbell BL, Katz JL | title = Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 3 | pages = 1088–1096 | date = June 2006 | pmid = 16478825 | doi = 10.1124/jpet.105.100594 | s2cid = 28919339 }} |
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*Richard H. Kline, Jr., Jeremy Wright, Kristine M. Fox, and Mohyee E. Eldefrawi. Synthesis of 3- Arylecgonine Analogues as Inhibitors of Cocaine Binding and Dopamine Uptake. ''Journal of Medicinal Chemistry'' 1990, (33): 2024-2027. |
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* {{cite journal | vauthors = Kline RH, Wright J, Fox KM, Eldefrawi ME | title = Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 7 | pages = 2024–2027 | date = July 1990 | pmid = 2362282 | doi = 10.1021/jm00169a036 }} |
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*Xu L, Trudell ML. ''Journal of Heterocyclic Chemistry''. 1996; 33: 2037. |
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* {{cite journal | vauthors = Xu L, Trudell ML | title = Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane. | journal = Journal of Heterocyclic Chemistry | date = November 1996 | volume = 33 | issue = 6 | pages = 2037–9 | doi = 10.1002/jhet.5570330676 }} |
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{{refend}} |
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{{Phenyltropanes}} |
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{{Stimulants}} |
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{{Stimulants}} |
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{{Monoamine reuptake inhibitors}} |
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{{Dopaminergics}} |
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{{Phenyltropanes}} |
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