Structure–Activity Relationship Studies of Hemicholinium (HC-3) Congeners

Joseph G. Cannon, Teresa M.L. Lee, Y. a. Chang, Alfred M. Nyanda, Bula Bhattacharyya, Jan R. Flynn, Tapan Chatterjee, Ranbir K. Bhatnagar, John Paul Long

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

In a continuing investigation of structural requirements for hemicholinium-like activity (inhibition of neuromuscular transmission due to inhibition of uptake of choline into nerve terminals), some additional molecular modifications of hemicholinium (“HC-3”; structure 1) were made. The target compounds were prepared by standard one- or two-step sequences. Noncyclic acetal moieties in general permitted retention of pharmacological activity, as did concomitant replacement of the central bi-phenyl “spacer” by other bulky cyclic groupings and replacement of the oxazinium rings by piperidine or 4-methylpiperidine. However, these modifications generally produced compounds of a lower potency. Replacement of the biphenyl moiety of HC-3 with polyalkylene chains permitted retention of a considerable degree of activity. In these target compounds, the two quaternary nitrogens can exist the same distance apart (approximately 14 Å) as in the hemicholinium molecule. The ditertiary amino congener of a pharmacologically active bis-quaternary oxazinium compound was almost completely inactive. To date, only one tertiary amine has been found which displays a significant degree of hemicholinium-like activity.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume5
Issue number6
DOIs
StatePublished - Jun 1988

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Keywords

  • hemicholinium
  • inhibition of choline uptake
  • neuromuscular inhibition

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Cannon, J. G., Lee, T. M. L., Chang, Y. A., Nyanda, A. M., Bhattacharyya, B., Flynn, J. R., Chatterjee, T., Bhatnagar, R. K., & Long, J. P. (1988). Structure–Activity Relationship Studies of Hemicholinium (HC-3) Congeners. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, 5(6), 359-364. https://doi.org/10.1023/A:1015955527100