Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling's clathrate hypothesis
Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling's clathrate hypothesis
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DOI：
10.1016/j.ejmech.2012.02.003
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发表时间：
2012-05-01
影响因子：
6.7
通讯作者：
Scott, K. R.
中科院分区：
文献类型：
--
作者：
Jackson, Patrice L.;Hanson, Clive D.;Scott, K. R.
测定了3-（（5-甲基异恶唑-3-基）氨基）-5-甲基环己-2-烯酮（12 b）和3-（（5-甲基异恶唑-3-基）氨基）-5，5-二甲基环己-2-烯酮（12 c）的X-射线晶体结构，并与它们在小鼠和大鼠体内的抗惊厥活性进行了关联。提出了类似物的毒性假说。此外，合成了一系列5-甲基-N-（3-氧代环己-1-烯基）-异恶唑-3-甲酰胺类化合物，并对其抗惊厥活性进行了评价。将这些化合物与相应的氨基和氨甲基烯胺酮的活性进行比较。另外的研究涉及活性异恶唑4-（5-甲基异恶唑-3-基-氨基）-6-甲基-2-氧代-环己-3-烯羧酸叔丁酯（4f）的三氟甲基类似物的合成和评价。由Elsevier Masson SAS出版。
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). Published by Elsevier Masson SAS.