CTDP-32476

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CTDP-32476
Identifiers
  • (2R)-2-[(1R)-1-(4-chlorophenyl)-3-methylbutyl]piperidine
CAS Number
PubChem CID
ChemSpider
E number{{#property:P628}}
CompTox Dashboard (EPA)
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Chemical and physical data
FormulaC16H24ClN
Molar mass265.83 g·mol−1
3D model (JSmol)
  • CC(C)C[C@H]([C@@H]1CCCCN1)C2=CC=C(C=C2)Cl
  • InChI=1S/C16H24ClN/c1-12(2)11-15(16-5-3-4-10-18-16)13-6-8-14(17)9-7-13/h6-9,12,15-16,18H,3-5,10-11H2,1-2H3/t15-,16-/m0/s1
  • Key:UWHKVOABKKOHHU-HOTGVXAUSA-N

CTDP-32476 is an atypical, highly potent dopamine reuptake inhibitor investigated as a potential pharmacotherapy for cocaine addiction.[1][2][3] Unlike cocaine, which acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) by rapidly blocking reuptake of all three monoamines, CTDP-32476 is highly selective for the dopamine transporter (DAT) and does not significantly block either the serotonin or norepinephrine transporters. Its slow-onset and long-duration effects are thought to result from pharmacokinetic properties such as delayed absorption and slower diffusion across the blood-brain barrier (BBB), resulting in a much lower risk of abuse compared to cocaine.[citation needed] However, the evidence for slower BBB penetration is indirect and inferred primarily from behavioral and neurochemical profiles rather than direct permeability measurements. While agonist-replacement therapies have been effective for opiate and nicotine dependence, there is currently no reliably successful agent for cocaine addiction.[4]

The two enantiomers were labeled ATDP-34209 and ATDP-34210. Their absolute configurations were determined by X-ray crystallography. ATDP-34210 is the RR enantiomer corresponding to the active RR enantiomer of methylphenidate. Both the SS and the RR enantiomers have similar activities.[3]

Synthesis

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The starting quaternary phosphonium salt is called isobutyltriphenylphosphonium bromide (1a). Treatment with phenyl lithium gives the corresponding ylide p-(i-butylidene)triphenylphosphorane (1b). The Wittig reaction with 2-(4-chlorobenzoyl)pyridine (2) gives a pair of geometric isomers: 2-[(E)-1-(4-chlorophenyl)-3-methylbut-1-enyl]pyridine (3) & 2-[(Z)-1-(4-chlorophenyl)-3-methylbut-1-enyl]pyridine (4). Catalytic hydrogenation completes the synthesis (5).[3]

The geometric isomers can be resolved using the corresponding acetylleucine enantiomers.[3]

See also

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References

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