2-Acetyl-3-hydroxy-5-methoxy-4,4,6-trimethyl-cyclohexa-2,5-dienone | 849599-28-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Acetyl-3-hydroxy-5-methoxy-4,4,6-trimethyl-cyclohexa-2,5-dienone
• CAS: 849599-28-6
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: BQAHSEFFCRXHOR-UHFFFAOYSA-N

物化性质

• 沸点：
  390.7±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-Acetyl-3-hydroxy-5-methoxy-4,4,6-trimethyl-cyclohexa-2,5-dienone 在 硫酸 、 碘 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 C₂₃H₂₀O₄
  参考文献：
  名称：

  Antitumor Agents. 284. New Desmosdumotin B Analogues with Bicyclic B-Ring as Cytotoxic and Antitubulin Agents

  摘要：

  We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI(50) values of 0.8-2.1 mu M. In contrast, 1 analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) over-expressing multidrug resistant cell line. We have now prepared and evaluated, 1 analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI(50) values of 0.06-0.16 mu M, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC(50) value of 2.0 mu M and colchicine binding by 7896 as well as cellular microtubule polymerization and spindle formation.

  DOI：

  10.1021/jm1011947
• 作为产物：
  描述：

  2-acetyl-3,5-dihydroxy-4,6,6-trimethylcyclohexa-2,4-dien-1-one 、 三甲基硅烷化重氮甲烷 生成 2-Acetyl-3-hydroxy-5-methoxy-4,4,6-trimethyl-cyclohexa-2,5-dienone
  参考文献：
  名称：

  Antitumor Agents 260. New Desmosdumotin B Analogues with Improved In Vitro Anticancer Activity

  摘要：

  Sixteen analogues (3-16, 33, and 48) of the unique flavonoid desmosdumotin B (1) were prepared and evaluated as in vitro inhibitors of the human KB cancer cell line and its MDR subclone, KB-VIN. 6,8,8-Triethyl analogues 10-13 showed enhanced KB-VIN selectivity. In particular, 4'-alkyl derivatives 11 (4'-Me) and 12 (4'-Et) showed significant ED50 values of 0.03 and 0.025 mu g/mL, respectively, against KB-VIN with selectivities of > 460- and 320-fold compared with that of KB. This report is the first to describe compounds showing such high activity against MDR cells versus non-MDR cells. The unique activity of 1-analogues is likely MDR-mediated because cotreatment with verapamil, a P-gp inhibitor, partially reversed the selective toxicity of both 1 and 10. Interestingly, only 1-analogues with a naphthalene B-ring (8 and 14) showed significant cytotoxic activity against KB; and other cancer cell lines. Thus, 1-analogues might be a new class of potent drug candidates, especially as 11 and 12 express direct selective action against tumors expressing MDR.

  DOI：

  10.1021/jm701208v

文献信息

• Antitumor agents 243. Syntheses and cytotoxicity of desmosdumotin C derivatives
  作者：Kyoko Nakagawa-Goto、Jiu-Hong Wu、Kenneth F. Bastow、Chin-Chung Wu、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2004.12.040

  日期：2005.3

  New analogs of desmosdumotin C (1), in which other aromatic rings replaced the terminal phenyl group and the A-ring was modified, were synthesized. Compounds 2-9, 13, and 16 were evaluated in vitro against human tumor cell replication. The 4-bromophenyl analog (2) showed potent cytotoxic activity in four different tumor cell lines.

  合成了desmosdumotin C（1）的新类似物，其中其他芳香环取代了末端苯基，并且对A环进行了修饰。在体外针对人肿瘤细胞复制评估了化合物2-9、13和16。4-溴苯基类似物（2）在四种不同的肿瘤细胞系中显示出强大的细胞毒性活性。
• Desmosdumotins, the Method for Preparing the Same and Use as Anti-Tumor or Anti-AIDS Agents
  申请人：Wu Jiuhong

  公开号：US20090233998A1

  公开（公告）日：2009-09-17

  This invention discloses the method for preparing desmosdumotin C, the series of desmosdumotin C derivatives and their manufactures, and the total synthesis of desmosdumotin B. The invention also discloses uses of the derivatives and pharmaceutical compositions containing the same in preparation of medicines for treatment of tumor or AIDS.

  本发明揭示了制备desmosdumotin C的方法、desmosdumotin C衍生物系列及其制备方法，以及desmosdumotin B的全合成方法。本发明还揭示了衍生物的用途和含有它们的制药组合物，用于制备治疗肿瘤或艾滋病的药物。
• Antitumor Agents 259. Design, Syntheses, and Structure−Activity Relationship Study of Desmosdumotin C Analogs
  作者：Kyoko Nakagawa-Goto、Tzu-Hsuan Chen、Chieh-Yu Peng、Kenneth F. Bastow、Jiu-Hong Wu、Kuo-Hsiung Lee

  DOI：10.1021/jm0702534

  日期：2007.7.1

  Desmosdumotin C (1) and its analogs previously showed potent, selective in vitro anticancer activity. To explore structure-activity relationships of 1 and further increase potency and selectivity, 15 novel analogs (7-15 and 21-26) were synthesized and evaluated for cytotoxity against several human tumor cell lines, as well as inhibition of human endothelial (HUVEC) replication. 4-Bromo-3',3',5'-tripropyl analog 26 showed significant cytotoxity against A549, A431, 1A9, and HCT-8 with ED50 values of 1.0, 1.2, 0.9, and 1.3 mu g/mL, respectively. Compound 26 also strongly inhibited the growth of matched tumor cells, KB-VIN and its parent cell KB. Furthermore, analogs 13 and 21 were over 5-fold more potent against KB-VIN than KB. Bromination of ring-B and tripropyl functionalization of ring-A enhanced activity, while alkylation of ring-B promoted KB-VIN/KB selectivity. 2-Furyl analog 16 showed selective activity against HUVEC, suggesting that it may have potential as a new prototype for angiogenesis inhibition.
• US7834216B2
  申请人：——

  公开号：US7834216B2

  公开（公告）日：2010-11-16