Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues

Andrew Thurkauf, Brian De Costa, Shun Ichi Yamaguchi, Mariena V. Mattson, Arthur E. Jacobson, Kenner C. Rice, Michael A Rogawski

Research output: Contribution to journalArticle

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Abstract

Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay. In addition, we determined the binding affinities of the compounds for PCP acceptor sites in rat brain membranes labeled with [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine. Many of the analogues were protective against MES seizures (ED50s of 5-41 mg/kg, ip) and all of these compounds caused motor toxicity. The potencies in the motor toxicity and MES seizure tests showed a moderate correlation with the affinities for PCP sites. Several analogues exhibited a greater separation of potencies in the motor toxicity and MES seizure tests than did the parent compound PCA. These were obtained by (i) 3-methylation of the cyclohexyl ring trans to the phenyl ring, (ii) methoxylation at the ortho position on the phenyl ring, and (iii) contraction of the cyclohexane ring to form the corresponding cyclopentane.

Original languageEnglish (US)
Pages (from-to)1452-1458
Number of pages7
JournalJournal of Medicinal Chemistry
Volume33
Issue number5
StatePublished - 1990
Externally publishedYes

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Electroshock
Phencyclidine
Anticonvulsants
Toxicity
Seizures
Passive Cutaneous Anaphylaxis
tenocyclidine
Cyclopentanes
Methylation
Rats
Assays
Brain
Derivatives
Membranes
1-phenylcyclohexylamine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Thurkauf, A., De Costa, B., Yamaguchi, S. I., Mattson, M. V., Jacobson, A. E., Rice, K. C., & Rogawski, M. A. (1990). Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues. Journal of Medicinal Chemistry, 33(5), 1452-1458.

Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues. / Thurkauf, Andrew; De Costa, Brian; Yamaguchi, Shun Ichi; Mattson, Mariena V.; Jacobson, Arthur E.; Rice, Kenner C.; Rogawski, Michael A.

In: Journal of Medicinal Chemistry, Vol. 33, No. 5, 1990, p. 1452-1458.

Research output: Contribution to journalArticle

Thurkauf, A, De Costa, B, Yamaguchi, SI, Mattson, MV, Jacobson, AE, Rice, KC & Rogawski, MA 1990, 'Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues', Journal of Medicinal Chemistry, vol. 33, no. 5, pp. 1452-1458.
Thurkauf A, De Costa B, Yamaguchi SI, Mattson MV, Jacobson AE, Rice KC et al. Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues. Journal of Medicinal Chemistry. 1990;33(5):1452-1458.
Thurkauf, Andrew ; De Costa, Brian ; Yamaguchi, Shun Ichi ; Mattson, Mariena V. ; Jacobson, Arthur E. ; Rice, Kenner C. ; Rogawski, Michael A. / Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogues. In: Journal of Medicinal Chemistry. 1990 ; Vol. 33, No. 5. pp. 1452-1458.
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