Synthesis and α(1)-adrenoceptor antagonist activity of tamsulosin analogues
| Autor: | Gianni Sagratini, Dario Giardinà, Michela Buccioni, Piero Angeli, Gabriella Marucci, Carlo Melchiorre, Ugo Gulini, Elena Poggesi |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Tamsulosin medicine.medical_specialty Pharmacology Chemical synthesis Structure-Activity Relationship Lower urinary tract symptoms Internal medicine Receptors Adrenergic alpha-1 Drug Discovery medicine Structure–activity relationship Potency Animals Rats Wistar Sulfonamides Molecular Structure Chemistry Organic Chemistry Antagonist Stereoisomerism General Medicine Hyperplasia medicine.disease Rats Endocrinology Adrenergic alpha-1 Receptor Antagonists Antagonism medicine.drug |
| Popis: | Tamsulosin (-)-1 is the most utilized α(1)-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)-1 analogues (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for α(1)-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α1A-than α1D-and α1B-adrenoceptors, and a 12-fold higher potency at α1A-adrenoceptors with respect to the α1B subtype, may have improved uroselectivity compared to (-)-1. |
| Databáze: | OpenAIRE |
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