Analogues of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds.
J Med Chem
; 34(10): 3065-74, 1991 Oct.
Article
em En
| MEDLINE
| ID: mdl-1920357
ABSTRACT
Oxybutynin chloride [4-(diethylamino)-2-butynyl alpha-cyclohexyl-alpha-hydroxybenzeneacetate hydrochloride, Ditropan] is widely used for the relief of symptoms in neurogenic bladder. This is a result of its combined anticholinergic, antispasmodic, and local anesthetic activities. In a study directed toward development of agents possessing the beneficial properties of oxybutynin, but having a longer duration of action, a series of metabolically more stable keto analogues of the parent ester, i.e. substituted 7-amino-1-hydroxy-5-heptyn-2-ones along with some analogues and derivatives, was prepared and evaluated for in vitro and in vivo antimuscarinic action in guinea pig preparations. Several members of the series were potent antimuscarinics having a longer duration of activity than that of oxybutynin in a guinea pig cystometrogram model. On the basis of its in vitro and in vivo antimuscarinic activity, coupled with a 5-fold greater duration of action than that of oxybutynin, 1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one (14b) was selected for clinical evaluation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Parassimpatolíticos
/
Bexiga Urinária
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Antagonistas Muscarínicos
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Ciclobutanos
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Alcinos
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Ácidos Mandélicos
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1991
Tipo de documento:
Article