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Pharmacy World and Science

, Volume 17, Issue 4, pp 120–125 | Cite as

Synthesis and pharmacology of a series of new organic nitrate esters

  • J. Bron
  • G. J. Sterk
  • J. F. van der Werf
  • H. Timmerman
Articles

Abstract

New organic nitrate esters, derived from structurally different (cyclo)aliphatic templates, were synthesized and pharmacologically investigated. Theirin vitro vascular smooth muscle relaxing activities and, occasionally,in vivo haemodynamic profiles were studied and compared to those of the clinically important nitrates, glyceryl trinitrate, isosorbide dinitrate and isosorbide-5-mononitrate. A number of compounds appeared to be even more potent than glyceryl trinitrate. Qualitative structure-activity relationships within the series of new compounds are discussed. In flexiblen-alkylene dinitrates, lipophilicity as well as chain length appears to affectin vitro activity. In semi-rigid cyclohexylene dinitrates, the number of atoms between and the configuration of the nitrate groups may play an important role. Finally, in cycloalkylene mononitrates neither the number of ring carbon atoms nor the lipophilicity clearly affects thein vitro activity. It is suggested that, apart from a limited involvement of compound lipophilicity, other factors such as differences in enzymatic conversion to a common putative bioactive species, nitric oxide, are responsible for the observed differences in activity.

Keywords

Alcohols Chemical synthesis Nitrates Pharmacology Structure-activity relationship Vasodilator agents 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1995

Authors and Affiliations

  • J. Bron
    • 1
  • G. J. Sterk
    • 2
  • J. F. van der Werf
    • 2
  • H. Timmerman
    • 3
  1. 1.Division of Byk Nederland BVCedona Pharmaceuticals BVRW Haarlemthe Netherlands
  2. 2.Cedona Pharmaceuticals BVHaarlemthe Netherlands
  3. 3.Leiden/Amsterdam Centre for Drug Research, Department of Pharmacochemistry, Faculty of ChemistryFree UniversityHV Amsterdamthe Netherlands

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