Enantiomeric resolution of some human aldosterone synthase [CYP 11 B2] inhibitors on derivatized polysaccharide chiral stationary phases

Abstract

Aldosterone synthase (CYP 11 B2) is a mitochrondrial cytochrome P450 enzyme catalyzing the last steps of aldosterone production in the adrenal cortex. A new pharmacological approach for the treatment of the aldosterone-induced effects in congestive heart failure and all forms of hyperaldosteronism could be achieved through the use of (CYP 11 B2) inhibitors. The chiral resolution of some of active compounds, namely 1-(4-pyridyl(methyl)tetralin (I), 7-chloro-1-(1-imidazolyl)tetralin (II), and 5-hydroxy-2-(4-pyridylmethyl)indane (III), on various polysaccharide derivative chiral stationary phases, namely Chiralcel OD, OJ, OC, and Chiralpak AD and AS, in normal phase mode was achieved. The mobile phase used was hexane/2-propanol/triethylamine (9:1:0.1 v/v/v). The flow rate of the mobile phase was 0.8 mL/min and the wavelengths of detection of compounds I, II, and III were set at 288, 271, and 254 nm, respectively. The chromatographic parameters: retention factor (k), selectivity (α), and resolution factor (Rs) were calculated. The chiral recognition mechanisms between these analytes and chiral selectors are discussed.