ISSN:
1432-1912
Keywords:
Nifedipine
;
Cat papillary muscle
;
Inotropic effects
;
Structure-activity relationship
;
Hansch analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. The effects on contractile activity of 2 series of nifedipine-derivatives were investigated in isolated, isotonically contracting cat papillary muscles. 2. For structure-activity studies the lipophilicity of all compounds was determined by means of reversed phase thin-layer chromatography. 3. Neither the ortho-NO2 group in a series of arylderivatives nor the methyl-esters in a series of esterderivatives were found to be essential for the typical effect of the nifedipine molecule on myocardial contractility. 4. Generally ortho-substituted derivatives induce a greater negative inotropic activity than meta-substituted derivatives. Para-substituted derivatives are the least active compounds. 5. In the group of ester-derivatives activity decreases when lipophilicity and/or volume of the substituent increases. 6. The quantitative analysis (Hansch analysis) revealed significant correlations between the negative inotropic effect and steric substituent parameters. Best correlations were obtained with: i) the minimum width, B 1 (ortho-substituted derivatives); ii) the van der Waals volume, V w (ester-substituted derivatives); iii) the experimentally or theoretically determined lipophilicity, R M or π, respectively (ester-derivatives). 7. It is concluded that-within a group of nifedipine derivatives-the negative inotropic effect depends mainly on steric and on lipophilic and/or steric substituent properties for aryl- and ester-derivatives, respectively. Electronic influences are not important for the biological activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00499876
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