methyl 4-benzylamino-6,6-dimethyl-2-oxocyclohex-3-en-1-oate | 142458-03-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-benzylamino-6,6-dimethyl-2-oxocyclohex-3-en-1-oate
• 英文别名: Methyl 4-(benzylamino)-6,6-dimethyl-2-oxocyclohex-3-ene-1-carboxylate
• CAS: 142458-03-5
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: PTZPPGJVUQMSDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 2-hydroxy-6,6-dimethyl-4-oxocyclohex-2-en-1-oate 、 苄胺 以 甲苯 为溶剂， 以79%的产率得到methyl 4-benzylamino-6,6-dimethyl-2-oxocyclohex-3-en-1-oate
  参考文献：
  名称：

  烯胺酯的合成，反应和初步评价

  摘要：

  这项工作的目的是设计具有潜在医学特性的烯胺酯。β-羟基酮酯与伯或仲胺之间的反应分别产生仲或叔烯胺酯。在酸性，碱性和中性介质中测定烯胺酯的紫外光谱。与中性介质相比，该光谱在酸性介质中具有七色移。烯胺酯为各种反应提供了亲核和亲电子位点。因此，烯胺酮酯仅转化为烯胺酰胺和O-烷基化产物。尽管烯胺酮酯通常耐金属氢化物还原，但一种无阻碍的烯胺酮酯可与硼氢化钠还原为醇。另一种烯胺酯与胍反应，得到相应的喹唑啉酮。由于烯胺酮系统中亲核和亲电子位点的多样性，烯胺酮酯具有作为反应中间体和药用化合物的巨大潜力。烯胺酮酯的初步评估显示了组胺能作用，子宫松弛特性和抗惊厥活性。

  DOI：

  10.1002/jps.2600830119

文献信息

• Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations
  作者：K. R. Scott、Ivan O. Edafiogho、Erica L. Richardson、Vida A. Farrar、Jacqueline A. Moore、Elizabeth I. Tietz、Christine N. Hinko、Hyejung Chang、Afif El-Assadi、Jesse M. Nicholson

  DOI：10.1021/jm00066a003

  日期：1993.7

  shown to be safer alternatives, the most notable was methyl 4-[(p-bromophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate, 13. Compound 13 had an ip ED50 of 4 mg/kg in the rat and a TD50 of 269 mg/kg, providing a protective index (TD50/ED50) of > 67. By variation in the ring size, additional aromatic substitutions and the synthesis of acyclic analogs, these newer compounds provide a more definitive insight

  该报告继续对4-[（对氯苯基）氨基] -6-甲基-2-氧代环己基-3-烯-1-酸酯1（ADD 196022）和甲基4-（苄基氨基）进行深入评估-6-甲基-2-氧代环己基-3-烯-1-酸酯，2个，两个有效的抗惊厥性烯胺酮。这些化合物采用杏仁核点燃模型进行评估。1和2都没有针对杏仁核点燃的癫痫发作的活性，进一步支持了角膜点燃的模型作为抗电击癫痫发作评估的确定工具，如先前报道。关于1的其他腹膜内（ip）数据显示，在100 mg / kg的24小时内有毒性。为了使毒性最小化，已经制备了几种活性类似物。在由抗癫痫药物开发（ADD）计划开发的特殊ip大鼠屏幕中，对这些新的类似物进行了评估，以防最大剂量10 mg / kg的电击惊厥（MES）和100 mg / kg的神经毒性。从该筛选中，显示出几种化合物是更安全的替代品，最引人注目的是4-[（（对-溴苯基）氨基] -6-甲基-2-氧代环己基-3-en-
• Functionalised enaminones and their use in heterocyclic synthesis
  作者：John V. Greenhill、Ibrahim Chaaban、Peter J. Steel

  DOI：10.1002/jhet.5570290602

  日期：1992.10

  A series of enaminones derived from 2,4-dioxocyclohexane carboxylic acid esters has been prepared. The use of some of the new derivatives in the synthesis of some quinazolones and imidazoloquinazolines is illustrated.

  已经制备了一系列衍生自2，4-二氧代环己烷羧酸酯的烯胺酮。说明了在一些喹唑酮和咪唑并喹唑啉的合成中某些新衍生物的使用。
• 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 and anticonvulsant activity of enaminones
  作者：Ivan O. Edafiogho、Christine N. Hinko、Hyejung Chang、Jacqueline A. Moore、Dianna Mulzac、Jesse M. Nicholson、K. R. Scott

  DOI：10.1021/jm00093a012

  日期：1992.7

  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.