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

Remko, M. Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors Chemical Papers, Vol.61, No. 2, 2007, 133-141

Document type: ńĆl√°nok z ńćasopisu / Journal Article
Collection: Chemical papers  

Author(s) Remko, M.
Title Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors
Journal name Chemical Papers
Publication date 2007
Year available 2007
Volume number 61
Issue number 2
ISSN 0366-6352
Start page 133
End page 141
Place of publication Poland
Publisher Versita
Collection year 2007
Language english
Subject 250000 Chemical Sciences
250300 Organic Chemistry
Abstract/Summary 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.
 
Related Links
Link Description
http://www.springerlink.com/content/f73722780j006q70/?p=29f8b7eb72e44714935a0...   fulltext  
 
 
User Comments
 
Access Statistics: 0 Abstract Views Detailed Statistics
Created: Wed, 17 Mar 2010, 08:24:51 CET by Jana Taptińćov√° . Detailed History