title: Enantiomers of 8-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydro-3-oxo-2H- (1,4)benzothiazine: racemic resolution, chiral synthesis and biological activity.
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.
authors.affiliation: Istituto di Chimica Farmaceutica e Technica Farmaceutica, Università di Perugia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Schiaffella
authors.forename: R
authors.initials: R
authors.lastname: Fringuelli
authors.forename: V
authors.initials: V
authors.lastname: Cecchetti
authors.forename: A
authors.initials: A
authors.lastname: Fravolini
authors.forename: P
authors.initials: P
authors.lastname: Angeli
authors.forename: G
authors.initials: G
authors.lastname: Marucci
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002354:Carteolol / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D013843:Thiazines; C068678:8-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydro-3-oxo-2H-(1,4)-benzothiazine; D002354:Carteolol