Abstract
We report the resolution of racemic (+/-)-1 with (R)-(+)-methylbenzyl isocianate and the synthesis of (R)-1 and (S)-1 via Sharpless chiral epoxidation. The enantio- and tissue-selectivity of such enantiomers, as beta- and alpha-adrenoceptor antagonists, were studied. Compound 1, while confirming the potent beta-blocking activity, displayed a modest enantio-selectivity towards beta 1- and beta 2-adrenoceptors. All the compounds displayed no activity as alpha-adrenoceptor blockers.
MeSH terms
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / pharmacology
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Adrenergic beta-Antagonists / chemical synthesis*
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Adrenergic beta-Antagonists / pharmacology
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Animals
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Carteolol / pharmacology
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Electric Stimulation
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Guinea Pigs
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In Vitro Techniques
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Magnetic Resonance Spectroscopy
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Myocardial Contraction / drug effects
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Rats
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Stereoisomerism
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Thiazines / chemical synthesis*
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Thiazines / pharmacology
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Trachea / drug effects
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Vas Deferens / drug effects
Substances
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Adrenergic alpha-Antagonists
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Adrenergic beta-Antagonists
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Thiazines
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8-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydro-3-oxo-2H-(1,4)-benzothiazine
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Carteolol