Synthesis of new (arylcarbonyloxy)aminopropanol derivatives and the determination of their physico-chemical properties

Jan Tengler, Iva Kapustíková 1 , Ondřej Stropnický 1 , Petr Mokrý 1 , Michal Oravec 3 , Jozef Csöllei 1 , and Josef Jampílek 1
  • 1 Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical sciences Brno, 612 42, Brno, Czech Republic
  • 2 Medis International a.s, 747 23, Bolatice, Czech Republic
  • 3 Global Change Research Centre AS CR, 603 00, Brno, Czech Republic

Abstract

Eight hydrochlorides of 3-{2-[(2/4-fluorophenoxy)-ethylamino]}-2-hydroxypropyl-4-alkoxybenzoates and four hydrochlorides of 3-tert-butylamino-2-hydroxypropyl-4-butoxybenzoates were prepared as potential antagonists of the β1-adrenergic receptor (beta-blockers). A multistep synthesis of these compounds is described as well as their detailed analytical characterization. The pharmacokinetic properties of these weak base compounds are significantly influenced by their acid-base dissociation constant, pK a. The knowledge of this value is crucial for new drug development. This paper is aimed at developing a methodology that utilizes pH-dependent 1H NMR spectroscopy for its routine analysis. The selected predicted physico-chemical parameters of the new (arylcarbonyloxy)aminopropanols (i.e., aryloxyaminopropanol derivatives) were compared with the model drugs esmolol and flestolol.

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