ethyl 4-hydroxy-2-oxo-6-methylcyclohex-3-ene-1-carboxylate | 67174-68-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-hydroxy-2-oxo-6-methylcyclohex-3-ene-1-carboxylate
• 英文别名: ethyl-4-hydroxy-6-methyl-2-oxo-3-cyclohexene-1-carboxylate；ethyl 4-hydroxy-6-methyl-2-oxocyclohex-3-en-1-oate；4-carbethoxy-5-methylcyclohexane-1,3-dione；ethyl 4-hydroxy-6-methyl-2-oxo-3-cyclohexene-1-carboxylate；2,3-Dihydro-o-orsellinsaeure-ethylester
• CAS: 67174-68-9
• 化学式: C₁₀H₁₄O₄
• mdl: MFCD00010807
• 分子量: 198.219
• InChiKey: GABAYOQGPJPKDK-UHFFFAOYSA-N

物化性质

• 熔点：
  91-93 °C(lit.)
• 稳定性/保质期：

  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.18
• 重原子数：
  14.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  3.0

安全信息

• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38

反应信息

• 作为反应物：
  描述：

  ethyl 4-hydroxy-2-oxo-6-methylcyclohex-3-ene-1-carboxylate 在 sodium hydroxide 、 硫酸 作用下， 生成 5-甲基环己烷-1,3-二酮
  参考文献：
  名称：

  Synthesis and anticonvulsant activity of enaminones

  摘要：

  A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of > 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

  DOI：

  10.1021/jm00093a012
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 反式-2-丁烯酸乙酯 在 sodium methylate 作用下， 生成 ethyl 4-hydroxy-2-oxo-6-methylcyclohex-3-ene-1-carboxylate
  参考文献：
  名称：

  Synthesis and anticonvulsant activity of enaminones

  摘要：

  A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of > 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

  DOI：

  10.1021/jm00093a012

文献信息

• Synthesis, neuronal activity and mechanisms of action of halogenated enaminones
  作者：Ivan O. Edafiogho、Mohamed G. Qaddoumi、Kethireddy V.V. Ananthalakshmi、Oludotun A. Phillips、Samuel B. Kombian

  DOI：10.1016/j.ejmech.2014.02.002

  日期：2014.4

  Due to the excellent anticonvulsant activity of previously synthesized halogenated enaminones, more disubstituted analogs were synthesized and evaluated in vitro. The new enaminones either had no effect, depressed, or enhanced population spike (PS) amplitude in the rat hippocampus in a concentration-dependent manner. Structure–activity relationship (SAR) analysis indicated that compounds 21 and 25

  由于先前合成的卤代烯胺酮具有出色的抗惊厥活性，因此合成了更多的双取代类似物并进行了体外评估。在大鼠海马中，新的烯胺酮要么没有作用，要么没有抑制，或者没有增强，但浓度依赖性。结构-活性关系（SAR）分析表明，化合物21和25（具有二溴取代基）是等价的，并且比化合物2（具有二氯取代基）更有效，其中化合物25是所有测试化合物中最有效的。二碘代衍生物30和31测试对PS没有产生显着影响。对于PS抑郁症，环己烯酮环上的苯基取代产生最有效的化合物25。压抑PS的类似物还压抑了诱发的兴奋性突触后电流（EPSC）和动作电位触发频率。从烯胺酯的环己烯酮环上的6位上除去苯基或甲基，制得显示出前惊厥作用的化合物28。C log P值与卤代烯胺酮的抗惊厥活性之间没有直接关系。抗惊厥活性的机制是通过增强细胞外GABA间接抑制兴奋性突触传递，以及直接抑制神经元动作电位的激发。
• SILVER BETA-KETOCARBOXYLATE, MATERIAL COMPRISING THE SAME FOR FORMING SILVER METAL, AND USE THEREOF
  申请人：OSAKA UNIVERSITY

  公开号：EP1905756A1

  公开（公告）日：2008-04-02

  It is an object to provide a novel material that can quickly form metal silver even at a low temperature of approximately 210°C or less. This serves as a metal silver forming material that includes a silver β-ketocarboxylate. By heating this forming material, it is possible to form metal silver quickly even at a low temperature of approximately 210°C or less. Examples of the silver β-ketocarboxylate include silver isobutyrylacetate, silver benzoylacetate, silver acetoacetate, silver propionylacetate, silver α-methylacetoacetate, and silver α-ethylacetoacetate.

  我们的目标是提供一种新型材料，即使在约 210°C 或更低的低温下也能快速形成金属银。这种金属银成型材料包括一种β-酮羧酸银。通过加热这种成型材料，即使在约 210°C 或更低的低温下，也能快速形成金属银。β-酮羧酸银的例子包括异丁酰乙酸银、苯甲酰乙酸银、乙酰乙酸银、丙酰乙酸银、α-甲基乙酰乙酸银和α-乙基乙酰乙酸银。
• Anticonvulsant evaluation and mechanism of action of benzylamino enaminones
  作者：Ivan O. Edafiogho、Kethireddy V.V. Ananthalakshmi、Samuel B. Kombian

  DOI：10.1016/j.bmc.2006.03.049

  日期：2006.8

  The mechanism of anticonvulsant action was evaluated for the benzylamino enaminones. The most potent enaminone in this series was the unsubstituted benzylamine analog (30; methyl 4-benzylamino-6-methyl-2-oxocyclohex-3-en-1-oate) which had an oral effective dose (EDSO) in rats of 27 mg/kg against maximal electroshock seizures, and a concentration 10-fold less than this dose depressed excitatory synaptic transmission, and action potential firing in the rat brain in vitro. (c) 2006 Elsevier Ltd. All rights reserved.
• Ultraviolet spectroscopy of anticonvulsant enaminones
  作者：I.O Edafiogho、O.A Phillips、M Abdel-Hamid、A.A.M Ali、W.C Matowe、A El-Hashim、S.B Kombian

  DOI：10.1016/s0968-0896(01)00314-5

  日期：2002.3

  The ultraviolet (UV) spectra of selected enaminones were determined in acidic, alkaline and neutral media and compared to their anticonvulsant activities. The wavelength of maximum absorption and molar absorptivity were compared with the anticonvulsant activity of the selected secondary and tertiary enaminones. and general inferences were made. The UV spectra of the enaminones had hypsochromic shifts in acidic media in comparison with neutral media. Generally, a small hypsochromic shift occurred in alkaline media when compared to the neutral solutions of the enaminones. The tertiary enaminones absorbed UV light at longer wavelength than the secondary enaminones in acidic, neutral and alkaline media. In particular, the tertiary enaminones displayed absorption at the higher end and secondary enaminones towards the lower end of the UV wavelength range 292-315 nm in aqueous media. Tertiary enaminones (30-33) which were devoid of the NH proton were found to be uniformly inactive in a mouse model of electroshock seizures, while some secondary enaminones (1, 5-8, 12. 16, 18, 20, 23-25, 28 and 29) had anticonvulsant activity. Thus the NH group of secondary enaminones is very important for anticonvulsant activity, and this agrees with an already established trend in proton NMR spectroscopy. In addition, the pares-substitution on the phenyl group in some enaminones result in higher molar absorptivity (a) values that enhance anticonvulsant activity. These results indicate that the anticonvulsant activity of enaminones is not due to electronic effect alone, but is probably due to a combination of factors including electronic and steric effects. lipophilicity, and hydrogen bonding. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis, characterization, and anticonvulsant activity of enaminones. Part 5: Investigations on 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-one derivatives
  作者：Mia L. Laws、Ralph R. Roberts、Jesse M. Nicholson、Raymond Butcher、James P. Stables、Angela M. Goodwin、Carlynn A. Smith、K.R. Scott

  DOI：10.1016/s0968-0896(98)80009-6

  日期：1998.12

  A new series of anticonvulsant 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones is herein reported. 2-Aminothiophenols underwent cyclocondensation with 4-carboalkoxy-5-methylcyclohexane-1,3-diones in refluxing dimethylsulfoxide (DMSO) to yield 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones, 4a-k. In the case of the carbo-tert-butoxy derivatives (4c and 4k) prolonged reaction times led to the isolation of the respective 3-unsubstituted-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones (41 and 4m) instead. Significant anticonvulsant activity was displayed by these analogues, most particularly 4k, which was active at 30 mg/kg intraperitoneally tip) in mice in the maximal electroshock seizure (MES) evaluation, with no toxicity noted at dosages up to 300 mg/kg. Oral (po) rat evaluation of 4k in the MES evaluation provided an ED50 Of 17.60 mg/kg, with no toxicity noted at dosages up to 500 mg/kg, providing a protective index (PI = TD50/ED50) > 28.40. These compounds represent the first reported series of phenothiazines which possess anticonvulsant activity. (C) 1998 Elsevier Science Ltd. All rights reserved.