(R)-(-)-10-Methyl-11-hydroxyaporphine: A Highly Selective Serotonergic Agonist

Joseph G. Cannon, Prem Mohan, Jacek Bojarski, John Paul Long, Ranbir K. Bhatnagar, Paul A. Leonard, Jan R. Flynn, Tapan Kumar Chatterjee

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Abstract

Prior work in these laboratories identified (±)-5-hydroxy-6-methyl-2-(di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

Original languageEnglish (US)
Pages (from-to)313-318
Number of pages6
JournalJournal of Medicinal Chemistry
Volume31
Issue number2
DOIs
Publication statusPublished - Dec 1 1988

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Cannon, J. G., Mohan, P., Bojarski, J., Long, J. P., Bhatnagar, R. K., Leonard, P. A., ... Chatterjee, T. K. (1988). (R)-(-)-10-Methyl-11-hydroxyaporphine: A Highly Selective Serotonergic Agonist. Journal of Medicinal Chemistry, 31(2), 313-318. https://doi.org/10.1021/jm00397a007