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Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors

  • M. Remko EMAIL logo
Published/Copyright: April 1, 2007
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Chemical Papers
From the journal Chemical Papers Volume 61 Issue 2

Abstract

Computational chemical methods have been used to correlate the molecular properties of the 10 ACE inhibitors (captopril, enalapril, perindopril, lisinopril, ramipril, trandolapril, quinapril, fosinopril, benazepril, and cilazapril) and some of their active metabolites (enalaprilat, perindoprilat, ramiprilat, trandolaprilat, quinaprilat, fosinoprilat, benazeprilat, and cilazaprilat). The computed pK a values correlate well with the available experimental values. In the dicarboxylic ACE inhibitors, the carboxyalkyl carboxylate group of the ACE inhibitors studied is more acidic than the C-terminal carboxylate. However, at physiological pH = 7.4 both carboxyl groups of ACE inhibitors are completely ionized and the dicarboxyl-containing ACE inhibitors behave as strong acids. The available experimental partition coefficients of these ACE inhibitors investigated are well reproduced by the neural network-based ALOGPs and the fragment-based KoWWiN methods. All parent drugs (and prodrugs), with the exception of fosinopril, are compounds with low lipophilicity. Calculated pK a, lipophilicity, solubility, absorption, and polar surface area of the most effective ACE inhibitors for the prevention of myocardial infarction, perindopril and ramipril, were found similar. Therefore, it is probable that the experimentally observed differences in the survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older correlate closely to the physicochemical and pharmacokinetic characteristics of the specific ACE inhibitor that is used.

Keywords: ACE inhibitors; pK a ; lipophilicity; solubility; absorption; polar surface area

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Published Online: 2007-4-1
Published in Print: 2007-4-1

© 2007 Institute of Chemistry, Slovak Academy of Sciences

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https://doi.org/10.2478/s11696-007-0010-y
Keywords for this article
ACE inhibitors; pK a; lipophilicity; solubility; absorption; polar surface area

Articles in the same Issue

  1. Spectrophotometric determination of microamounts of quercetin based on its complexation with copper(II)
  2. Oxygen evolution on Ti/Co3O4-coated electrodes in alkaline solution
  3. The zeta potential of kaolin suspensions measured by electrophoresis and electroacoustics
  4. Fluidization behavior of oil-contaminated sand
  5. Software sensors for monitoring of a solid waste composting process
  6. Calcined Ni—Al layered double hydroxide as a catalyst for total oxidation of volatile organic compounds: Effect of precursor crystallinity
  7. Thermodynamic possibilities and constraints of pure hydrogen production by a chromium, nickel, and manganese-based chemical looping process at lower temperatures
  8. Death kinetics of Escherichia coli in goat milk and Bacillus licheniformis in cloudberry jam treated by ohmic heating
  9. Topochemical models for anti-HIV activity of 1-alkoxy-5-alkyl-6-(arylthio)uracils
  10. Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors
  11. Silver as anode in cryolite—alumina-based melts
  12. Multicomponent facile synthesis of novel dihydroazolopyrimidinyl carbamides
  13. Z. Platková, M. Polakovič, V. Štefuca, M. Vandáková, and M. Antošová: Selection of Carrier for Immobilization of Fructosyltransferase from Aureobasidium pullulans
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