Stereospecific effects of benzo[d]isothiazolyloxypropanolamine derivatives at beta-adrenoceptors: synthesis, chiral resolution, and biological activity in vitro
| Autor: | Matteo Incerti, Mara Comini, Cristina Pozzoli, Ornella Azzolina, Enzo Poli, Simona Collina, Elena Di Vittorio, Giovanni Morini, Daniela Rossi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Tris
Male Adrenergic Antagonists Stereochemistry Stereoisomerism Catalysis Analytical Chemistry Substrate Specificity Propanolamines chemistry.chemical_compound Ileum Drug Discovery Animals Heart Atria Spectroscopy Chromatography High Pressure Liquid Pharmacology Chromatography Circular Dichroism Organic Chemistry Enantioselective synthesis Biological activity Chiral resolution Rats Chiral column chromatography Thiazoles Enantiopure drug chemistry Enantiomer |
| Zdroj: | Chirality. 21(2) |
| ISSN: | 1520-636X |
| Popis: | We performed the asymmetric synthesis of four enantiopure benzo[d] isothiazo-3-or 5-yloxypropanolamine derivatives, previously described as competitive antagonists at beta-adrenoceptors. The chemical characterization of each enantiomer was accomplished by (1)H NMR and HPLC/DAD/CD. The direct chromatographic separation of the enantiomers via chiral HPLC was investigated. The best resolutions were achieved using cellulose tris (3,5-dimethylphenyl carbamate) (Chiralcel OD-H) and amylose tris (3,5-dimethylphenyl carbamate) (Chiralpak AD). The enantiomers obtained had enantiomeric purities suitable for biological assays. Tested in isolated rat cardiac and intestinal tissues to evaluate their effects at beta(1)- and beta(3)-adrenoceptors, the (S)-enantiomers revealed a higher degree of antagonism than (R)-enantiomers at both subtypes, even though their activity was greater at the cardiac beta(1)-subtype. The potent and cardiospecific antagonistic effect exerted by the compounds tested suggests that the benzisothiazole moiety could be an interesting scaffold for discovering new chiral beta-blocking drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text