9-(2-hydroxy-4,4-dimethyl-6-oxocyclohexyl)-7-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one | 221348-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohexyl)-7-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one
• 英文别名: 9-(2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-7-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one；9-(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1-yl)-7-methoxy-3,3-dimethyl-4,9-dihydro-2H-xanthen-1-one
• CAS: 221348-95-4
• 化学式: C₂₄H₂₈O₅
• 分子量: 396.483
• InChiKey: JRVWXXVRFDVNST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-羟基-5-甲氧基苯甲醛 、 5,5-二甲基-1,3-环己二酮 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 1.0h， 生成 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohexyl)-7-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one
  参考文献：
  名称：

  (9S)-9-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, a Selective and Orally Active Neuropeptide Y Y5 Receptor Antagonist

  摘要：

  （9S）-9-(2-羟基-4,4-二甲基-6-氧-1-环己烯-1-基)-3,3-二甲基-2,3,4,9-四氢-1H-呫吨-1-酮 ((S)-1) 被鉴定为一种选择性且具有口服活性的神经肽Y Y5受体拮抗剂。针对这一结构类别的构效关系研究显示，苯环上的有限取代是可以耐受的，而对环己酮部分的4,4-二甲基基团和呫吨酮部分的3,3-二甲基基团进行修饰略有提高其效力。在 Sprague-Dawley (SD) 大鼠中口服给予(S)-1后，其血浆浓度-时间曲线显示(S)-1在体内发生显著的外消旋作用，并且(S)-1的清除速率远快于(R)-1。在SD大鼠中，口服给予(RS)-1外消旋体的(S)-1作用持续时间是口服给予(S)-1后作用持续时间的两倍。在(S)-1和(RS)-1给药后，(S)-1的Cmax值相当，且(S)-1在SD大鼠中的脑血浆比值为0.34。在我们的急性D-Trp3,4-神经肽Y诱导的食物摄入模型中，(S)-1和(RS)-1均显示出强大且剂量依赖性的疗效。因此，使用(RS)-1适合需要(S)-1持续血浆暴露的研究。

  DOI：

  10.1021/jm8003587

文献信息

• l-Proline-accelerated, eco-friendly synthesis of 9-substituted-2,3,4,9-tetrahydro-1H-xanthen-1-ones under mild conditions
  作者：Davinder Prasad、Amreeta Preetam、Mahendra Nath

  DOI：10.1016/j.crci.2013.05.011

  日期：2013.12

  Résumé An efficient l-proline-accelerated synthesis of 9-substituted-2,3,4,9-tetrahydro-1H-xanthen-1-one derivatives has been accomplished via one-pot condensation of dimedone or 1,3-cyclohexanedione with substituted salicylaldehydes under mild reaction conditions. This protocol demonstrates several notable advantages, including operational simplicity, short reaction times, environmentally friendly conditions, no necessity of extraction and chromatographic purification steps, and high yields of the target products. Supplementary Materials: Supplementary material for this article is supplied as a separate file: mmc1.doc

  摘要 通过将二酮或1,3-环己烷二酮与取代的水杨 aldehyde 在温和反应条件下进行一锅缩合，实现了高效的 l-脯氨酸加速合成 9-取代-2,3,4,9-四氢-1H-香豆素-1-酮衍生物。该方案显示出若干显著优势，包括操作简单、反应时间短、环保条件、不需要提取和色谱纯化步骤以及高产率的目标产品。 补充材料： 本文章的补充材料作为单独文件提供：mmc1.doc
• (9<i>S</i>)-9-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1<i>H</i>-xanthen-1-one, a Selective and Orally Active Neuropeptide Y Y5 Receptor Antagonist
  作者：Nagaaki Sato、Makoto Jitsuoka、Takunobu Shibata、Tomoko Hirohashi、Katsumasa Nonoshita、Minoru Moriya、Yuji Haga、Aya Sakuraba、Makoto Ando、Tomoyuki Ohe、Hisashi Iwaasa、Akira Gomori、Akane Ishihara、Akio Kanatani、Takehiro Fukami

  DOI：10.1021/jm8003587

  日期：2008.8.1

  (9S)-9-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one ((S)-1) was identified as a selective and orally active neuropeptide Y Y5 receptor antagonist. The structure-activity relationship for this structural class was investigated and showed that limited substitution on the phenyl ring was tolerated and that modification of the 4,4-dimethyl group of the cyclohexenone and the 3,3-dimethyl group of the xanthenone parts slightly improved potency. The plasma concentration-time profile after oral administration of (S)-1 in Sprague-Dawley (SD) rats showed significant in vivo racemization of (S)-1 and that (S)-1 is cleared much more quickly than (R)-1. The duration of (S)-1 in SD rats after oral administration of (RS)-1 racemate was twice as long as that following oral administration of (S)-1. The Cm, values of (S)-1 after administration of (S)-1 and (RS)-1 were comparable, and the brain to plasma ratio for (S)-1 was 0.34 in SD rats. In our acute D-Trp34NPY-induced food intake model, both (S)-1 and (RS)-1 showed potent and dose-dependent efficacy. Therefore, the use of (RS)-1 is suitable for studies that require sustained plasma exposure of (S)-1.

  （9S）-9-(2-羟基-4,4-二甲基-6-氧-1-环己烯-1-基)-3,3-二甲基-2,3,4,9-四氢-1H-呫吨-1-酮 ((S)-1) 被鉴定为一种选择性且具有口服活性的神经肽Y Y5受体拮抗剂。针对这一结构类别的构效关系研究显示，苯环上的有限取代是可以耐受的，而对环己酮部分的4,4-二甲基基团和呫吨酮部分的3,3-二甲基基团进行修饰略有提高其效力。在 Sprague-Dawley (SD) 大鼠中口服给予(S)-1后，其血浆浓度-时间曲线显示(S)-1在体内发生显著的外消旋作用，并且(S)-1的清除速率远快于(R)-1。在SD大鼠中，口服给予(RS)-1外消旋体的(S)-1作用持续时间是口服给予(S)-1后作用持续时间的两倍。在(S)-1和(RS)-1给药后，(S)-1的Cmax值相当，且(S)-1在SD大鼠中的脑血浆比值为0.34。在我们的急性D-Trp3,4-神经肽Y诱导的食物摄入模型中，(S)-1和(RS)-1均显示出强大且剂量依赖性的疗效。因此，使用(RS)-1适合需要(S)-1持续血浆暴露的研究。
• Diethylamine-catalyzed environmentally benign synthesis of 1-oxo-hexahydroxanthenes and bis-coumarins at ambient temperature
  作者：Ravindra V. Kupwade、Kapil S. Pandit、Uday V. Desai、Makarand A. Kulkarni、Prakash P. Wadgaonkar

  DOI：10.1007/s11164-016-2464-4

  日期：2016.7

  environmentally benign protocol has been described for one-pot synthesis of 1-oxo-hexahydroxanthenes by pseudo three-component condensation between salicylaldehydes and dimedone, cyclohexane-1,3-dione or 5-methyl cyclohexane-1,3-dione using diethylamine as the catalyst. Based upon the mechanism of the reaction, the protocol has been extended towards the synthesis of tetraketones and bis-coumarins. Graphical Abstract

  摘要 已经描述了通过水杨醛与二甲酮，环己烷-1,3-二酮或5-甲基环己烷-1,3之间的假三组分缩合一锅合成1-氧代-六氢氧杂蒽的极其简单，经济和环境友好的方案。 -使用二乙胺作为催化剂的二酮。根据反应机理，该方案已扩展到四酮和双香豆素的合成。 图形概要