Modelling of absorption, distribution and physicochemical properties of AT1 receptor antagonists / Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1 receptorov

Ježko, Pavol; Žufková, Viera; Remko, Milan

doi:10.1515/afpuc-2015-0028

Abstract

The theoretical chemistry methods were used to elucidate absorption, distribution and physicochemical properties of AT₁ receptor antagonists and dual angiotensin II and endothelin A receptor antagonist (PS-433540). Computed partition coefficients (ALOGPS method) studied for drugs varied between 2.98 and 6.66. Neutral compounds are described as lipophilic drugs. Telmisartan is a drug with the highest lipophilicity. The neutral forms of the studied AT₁ receptor antagonists are practically insoluble in water, and their computed solubilities is in interval between 2.04 and 22.65 mg/l (ALOGpS method). The calculated pK_a values for tetrazolyle moiety are in the range 3.92-5.00 and for carboxylic moiety 3.12-5.50. Telmisartan (polar surface area = 72.95 A) and irbesartan (polar surface area = 87.14 A) belong to the AT₁ receptor antagonists with increased absorption.

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Modelling of absorption, distribution and physicochemical properties of AT1 receptor antagonists / Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1 receptorov

Abstract

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