Biology:WIN-35428

Short description: Chemical compound

WIN-35428

Clinical data
Other names	CFT, WIN 35,428
Legal status
Legal status	US: Schedule II
Identifiers
IUPAC name Methyl (1R,2S,3S,5S)-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number	50370-56-4 Y 77210-32-3
PubChem CID	105056
IUPHAR/BPS	4606
ChemSpider	94788 N
UNII	8ZT6KJ947T
ChEMBL	ChEMBL541252 N
Chemical and physical data
Formula	C16H20FNO2
Molar mass	277.339 g·mol−1
3D model (JSmol)	Interactive image
Specific rotation	-62.5°
Melting point	202 to 204 °C (396 to 399 °F)
SMILES CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)F)C(=O)OC
InChI InChI=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 N Key:QUSLQENMLDRCTO-YJNKXOJESA-N N
NY (what is this?)  (verify)

(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT, WIN 35,428) is a stimulant drug used in scientific research. CFT is a phenyltropane based dopamine reuptake inhibitor and is structurally derived from cocaine. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While the naphthalenedisulfonate salt is the most commonly used form in scientific research due to its high solubility in water, the free base and hydrochloride salts are known compounds and can also be produced. The tartrate is another salt form that is reported.

Uses

CFT was first reported by Clarke and co-workers in 1973. This drug is known to function as a "positive reinforcer" (although it is less likely to be self-administered by rhesus monkeys than cocaine). Tritiated CFT is frequently used to map binding of novel ligands to the DAT, although the drug also has some SERT affinity.

Radiolabelled forms of CFT have been used in humans and animals to map the distribution of dopamine transporters in the brain. CFT was found to be particularly useful for this application as a normal fluorine atom can be substituted with the radioactive isotope ¹⁸F which is widely used in Positron emission tomography. Another radioisotope-substituted analog [11C]WIN 35,428 (where the carbon atom of either the N-methyl group, or the methyl from the 2-carbomethoxy group of CFT, has been replaced with ¹¹C) 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 methylecgonidine with parafluorophenylmagnesium bromide, and also avoids the requirement for a licence to work with the restricted precursor ecgonine.

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 cocaine, in a similar manner to how methadone is used as a substitute for opiates in treating addiction.

Street drug

In August 2010, some media sources claimed that the designer drug Ivory Wave contained WIN 35428. However, samples of Ivory Wave have been found to contain MDPV, so the legitimacy of these claims remains unclear.

Legal status

CFT is not specifically scheduled in the United States, though it meets the statutory definition of an ecgonine derivative. Consequently, it is a Schedule II drug.

Toxicity

Administering 100 mg/kg of CFT to rats only resulted in convulsions being reported, whereas CIT had the ability to cause death at this dose.

See also

• WIN 35,065-2
• List of phenyltropanes
• List of cocaine analogues

Further reading

• "Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428)". Neuropharmacology 18 (12): 1009–1010. December 1979. doi:10.1016/0028-3908(79)90167-9. PMID 530372. 
• "Saturable (3H)cocaine binding in central nervous system of mouse". Life Sciences 27 (12): 1055–1062. September 1980. doi:10.1016/0024-3205(80)90029-6. PMID 6106874. 
• "Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane". Pharmacology, Biochemistry, and Behavior 39 (4): 1011–1013. August 1991. doi:10.1016/0091-3057(91)90067-c. PMID 1763097. 
• "Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor". Journal of Medicinal Chemistry 34 (5): 1728–1731. May 1991. doi:10.1021/jm00109a029. PMID 2033595. 
• "Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency". The Journal of Pharmacology and Experimental Therapeutics 260 (3): 1174–1179. March 1992. PMID 1545384. 
• "Chemistry, design, and structure-activity relationship of cocaine antagonists". Chemical Reviews 100 (3): 925–1024. March 2000. doi:10.1021/cr9700538. PMID 11749256. 
• "Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine". The Journal of Pharmacology and Experimental Therapeutics 317 (3): 1088–1096. June 2006. doi:10.1124/jpet.105.100594. PMID 16478825. 
• "Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake". Journal of Medicinal Chemistry 33 (7): 2024–2027. July 1990. doi:10.1021/jm00169a036. PMID 2362282. 
• "Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane.". Journal of Heterocyclic Chemistry 33 (6): 2037–9. November 1996. doi:10.1002/jhet.5570330676.