1-Methyl-3-propyl-4-(p-chlorophenyl)piperidine explained

1-Methyl-3-propyl-4-(p-chlorophenyl)piperidine is a drug developed by a team led by Alan Kozikowski, which acts as a potent dopamine reuptake inhibitor, and was developed as a potential therapeutic agent for the treatment of cocaine addiction.^[1] As with related compounds such as nocaine, it is a structurally simplified derivative of related phenyltropane compounds.^[2] Its activity at the serotonin and noradrenaline transporters has not been published, though most related 4-phenylpiperidine derivatives are relatively selective for inhibiting dopamine reuptake over the other monoamine neurotransmitters. While several of its isomers are active, the (3S,4S)-enantiomer is by far the most potent.^{[3] [4]} The rearranged structural isomer 2-[1-(4-chlorophenyl)butyl]piperidine is also a potent inhibitor of dopamine reuptake.^[5]

See also

• 4-Fluoropethidine
• Allylprodine
• JZ-IV-10
• N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate
• WY-46824

Notes and References

1. US . 6180648 . Kozikowski AP, Araldi GL . George Town University . 2001-01-30 . Analogs of cocaine .
2. Kozikowski AP, Araldi GL, Prakash KR, Zhang M, Johnson KM . Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters . Journal of Medicinal Chemistry . 41 . 25 . 4973–82 . December 1998 . 9836615 . 10.1021/jm9802564 .
3. Kozikowski AP, Araldi GL, Boja J, Meil WM, Johnson KM, Flippen-Anderson JL, George C, Saiah E . Chemistry and pharmacology of the piperidine-based analogues of cocaine. Identification of potent DAT inhibitors lacking the tropane skeleton . Journal of Medicinal Chemistry . 41 . 11 . 1962–9 . May 1998 . 9599245 . 10.1021/jm980028+ . 10.1.1.512.7158 .
4. Kozikowski AP, Araldi GL, Tamiz AP . Georgetown University . Monomeric and dimeric heterocycles, and therapeutic uses thereof . US . 6440996 . 2002-08-27 .
5. Froimowitz M, Gu Y, Dakin LA, Nagafuji PM, Kelley CJ, Parrish D, Deschamps JR, Janowsky A . Slow-onset, long-duration, alkyl analogues of methylphenidate with enhanced selectivity for the dopamine transporter . Journal of Medicinal Chemistry . 50 . 2 . 219–32 . January 2007 . 17228864 . 10.1021/jm0608614 .