کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1399397 1501165 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling’s clathrate hypothesis
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling’s clathrate hypothesis
چکیده انگلیسی

The x-ray crystal structure of 3-((5-methylisoxazol-3-yl)amino)-5-methylcyclohex-2-enone (12b) and 3-((5-methylisoxazolyl-3-yl)amino)-5,5-dimethylcyclohex-2-enone (12c) were determined and correlated to their anticonvulsant activity in mice and rats. A hypothesis for the toxicity of the analogs are advanced. In addition, a series of 5-methyl-N-(3-oxocyclohex-1-enyl)-isoxazole-3-carboxamides were synthesized and evaluated for anticonvulsant activity. These compounds were compared to the activity of the corresponding amino and aminomethyl enaminones. Additional investigation involved the synthesis and evaluation of a trifluoromethyl analog of the active isoxazole tert-butyl 4-(5-methisoxazol-3-yl-amino)-6-methyl-2-oxo-cyclohex-3-ene carboxylate (4f).

Clathrate formation of the anticonvulsant active dimethyl enaminone isoxazole analog (12c), assembled as a head-to-tail dimer.Figure optionsDownload as PowerPoint slideHighlights
► A novel series of carboxamide isoxazole enaminones were synthesized.
► All analogs reported were evaluated for anticonvulsant activity.
► X-ray crystal data proves formation of a clathrate, seen in compound 12c.
► The clathrate formation blocks access to the proposed active site.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 51, May 2012, Pages 42–51
نویسندگان
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