Analogs of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds
| العنوان: | Analogs of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds |
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| المؤلفون: | Lalita Noronha-Blob, Waclaw Janusz Rzeszotarski, J. P. Carter, Ciro J. Spagnuolo, Waid Pp, Carl Kaiser, Natalie Kj, Andrea C. Dupont, Vicki H. Audia, McPherson Dw |
| المصدر: | Journal of Medicinal Chemistry. 34:3065-3074 |
| بيانات النشر: | American Chemical Society (ACS), 1991. |
| سنة النشر: | 1991 |
| مصطلحات موضوعية: | medicine.drug_class, Hydrochloride, Guinea Pigs, Urinary Bladder, Muscarinic Antagonists, Pharmacology, Parasympatholytic, chemistry.chemical_compound, Oxybutynin Chloride, In vivo, Drug Discovery, medicine, Anticholinergic, Animals, Amines, Oxybutynin, Parasympatholytics, Stereoisomerism, Biological activity, Receptors, Muscarinic, Urinary Incontinence, chemistry, Alkynes, Mandelic Acids, Molecular Medicine, Carbachol, Female, Antispasmodic, Cyclobutanes, Muscle Contraction, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ec2308fd260160398bdc73dbe7f84a5Test https://doi.org/10.1021/jm00114a016Test |
| رقم الانضمام: | edsair.doi.dedup.....8ec2308fd260160398bdc73dbe7f84a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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