Within the framework of the study of the synthesis and high-performance liquid chromatography (HPLC) enantioseparation the series of 9 derivatives of 3-hydroxyphenylethanone was prepared by a well-tried method. The structure of the prepared compounds was confirmed on the basis of interpretation of the IR, UV, 1H NMR and 13C NMR spectra. An enantioseparation of prepared compounds was performed using HPLC on a native teicoplanin (Chirobiotic T) and the amylose tris (3,5-dimethylphenylcarbamate) (Chiralpak AD) chiral stationary phases, which is more suitable for the enantioseparation of all prepared compounds especially with heterocycles in the basic part of a molecule.
This article describes a preparation of some new compounds of the aryloxyaminopropanol type derived from 4-hydroxyphenylpropan- 1-one with phenylamino, cyclohexylamino and isobutylamino group in the hydrophilic part and methoxymethyl or ethoxymethyl substituent in the lipophilic part of the molecule. The purity of the prepared compounds was checked by thinlayer chromatography and the structure was confirmed on the basis of interpretation of the IR, UV, 1H NMR and 13C NMR spectra. An enantioseparation of the prepared compounds was performed by using high-performance liquid chromatography on an amylase tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) and native teicoplanin (Chirobiotic T). The chromatographic results such as retention, separation and resolution factors have shown that Chiralpak AD is more suitable for enantioseparation of some of the prepared compounds.
Synthesis and enantioseparation of derivatives of propranolol
Propranolol is one of the first prepared and in therapeutic praxis used beta- adrenolytics. In this paper novel derivatives of propranolol with cyclohexylamino and pyrrolidin-1-yl groups in hydrophilic part were prepared. HPLC-enantioseparation propranolol (as reference compound) and of the prepared derivatives has been achieved using a Chiralpak AD CSP based on the amylose tris (3,5-dimethylphenylcarbamate).(R)-enantiomer of the propranolol was prepared by stereoselective synthesis using Jacobsen catalyst.
Structural understanding of subtype specific ligand-binding pocket variations and interactions of ligand with receptor may facilitate design of novel selective drugs. To gain insights into the subtype selectivity of β-blockers we performed flexible molecular docking study to analyze the interaction mode of cardioselective phenoxyaminopropanol blocker into the β1 and β2-adrenergic receptor. The binding site analysis reveals a strong identity between important amino acid residues and interactions with ligand in orthosteric catecholamine- binding pocket. The differences in the binding mode of selective ligand have been identified in the extracellular region of receptor subtypes.