Synthesis of l-Carbethoxy-4-cyano-4-phenylpiperidine

Bercz, Christa V.; Ice, Rodney D.

doi:10.1002/jps.2600610833

Cited by 5 publications

(1 citation statement)

References 10 publications

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“…A mixture of H2O (1 mL) and sulfuric acid (2 mL) was added to compound 21 17 (2 g), and the resulting mixture was refluxed overnight. Solvent was removed under vacuum to produce a residue, the residue was dissolved in MeOH (20 mL), and concentrated sulfuric acid (3 mL) was added.…”

Section: -(4′-chlorophenyl)-4-carboxy-1-phenylpiperidine (22)mentioning

confidence: 99%

Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species

et al. 2003

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The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [K(i)(D2) = 33, K(i)(D3) = 200, K(i)(D4) = 11 nM; K(i)(D2)/K(i)(D4) = 3] and 9 [K(i)(D2) = 44, K(i)(D3) = 170, K(i)(D4) = 24 nM; K(i)(D2)/K(i)(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

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Section: -(4′-chlorophenyl)-4-carboxy-1-phenylpiperidine (22)mentioning

confidence: 99%