17-methyl-11,15-dioxa-cyclopenta[a]phenanthren-12-one

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17-methyl-11,15-dioxa-cyclopenta[a]phenanthren-12-one
• 英文别名: 14-methyl-12,17-dioxatetracyclo[8.7.0.02,7.011,15]heptadeca-1(10),2,4,6,8,11(15),13-heptaen-16-one
• 化学式: C₁₆H₁₀O₃
• 分子量: 250.254
• InChiKey: OREBRUVPHTUTTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17-methyl-11,15-dioxa-cyclopenta[a]phenanthren-12-one 在 甲酸 、 palladium 10% on activated carbon 、 三乙胺 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以30%的产率得到1-methyl-1H-benzo[h]furo[3,2-c]chromen-11(2H)-one
  参考文献：
  名称：

  Antitumor Agents. 272. Structure−Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues

  摘要：

  Neo-tanshinlactone (1) and its previously reported analogues, such as 2, are potent and selective in vitro antibreast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, with a better overall yield. Structure-activity relationships studies on these compounds revealed some key molecular determinants for this family of antibreast agents. Several derivatives (19-21 and 24) exerted potent and selective antibreast cancer activity with IC50 values of 0.3, 0.2, 0.1, and 0.1 mu g/mL, respectively, against the ZR-75-1 cell lines. Compound 24 was 2- to 3-fold more potent than I against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analogue 2 showed potent activity against it ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19-21 and 24 as clinical trial candidates is warranted.

  DOI：

  10.1021/jm1000858
• 作为产物：
  描述：

  4-羟基-2H-苯并[H]色烯-2-酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.17h， 生成 17-methyl-11,15-dioxa-cyclopenta[a]phenanthren-12-one
  参考文献：
  名称：

  Antitumor Agents. 254. Synthesis and Biological Evaluation of Novel Neo-tanshinlactone Analogues as Potent Anti-Breast Cancer Agents

  摘要：

  In our previous study, neo-tanshinlactone ( 1) showed potent and selective anti-breast cancer activity. To explore the SAR of 1, nine analogues (15-18, 24-28) were designed and synthesized. Together with 1 and tamoxifen (TAM), all newly synthesized compounds and some intermediates were evaluated for in vitro anticancer activity against several human tumor cell lines. Compounds without a ring D did not show promising activity, while compounds with a methylated furan ring D showed better activity than those with unsubstituted furan or hydroxy-dihydrofuran rings. Among all newly synthesized compounds, compound 15 with an ethyl group at the 4-position showed the best activity and selectivity with ED50 values of 0.45 and 0.18 mu g/mL against MCF-7 and ZR-75-1 (ER+) and 13.5 and 10.0 mu g/mL against MDA MB-231 and HS 587-1 (ER-), respectively. Furthermore, 15 also showed potent activity against SK-BR-3 (ER-, HER2+) with an ED50 value of 0.10 mu g/mL. Our preliminary SAR studies showed that a methylated furan ring D and the C-4 substituent in ring A are critical for anti-breast cancer activity. Further development of 1 and 15 as anti-breast cancer drug candidates is warranted.

  DOI：

  10.1021/jm060184d

文献信息

• [EN] NEO-TANSHINLACTONE AND ANALOGS AS POTENT AND SELECTIVE ANTI-BREAST CANCER AGENTS<br/>[FR] PUISSANTS ANTICANCEREUX SELECTIFS (CANCER DU SEIN) A BASE DE NEO-TANSHINLACTONE ET ANALOGUES
  申请人：UNIV NORTH CAROLINA

  公开号：WO2005087225A1

  公开（公告）日：2005-09-22

  Compounds of Formulae (I-II) are described : along with methods of using such compounds for the treatment of cancer and pharmeutical formulations thereof.

  化合物的公式（I-II）被描述：以及使用这些化合物治疗癌症的方法和药物配方。
• Total Synthesis of Neo-Tanshinlactones through a Cascade Benzannulation-Lactonization as the Key Step
  作者：Ketaki Ghosh、Raju Karmakar、Dipakranjan Mal

  DOI：10.1002/ejoc.201300102

  日期：2013.7

  The cascade annulation-lactonization of phthalides with α-carboxyfurylacrylates in the presence of lithium hexamethyldisilazide (LiHMDS) provides both convergent and semiconvergent regioselective syntheses of neo-tanshinlactones in moderate yields. This methodology also offers an avenue for the direct syntheses of hitherto unreported 6-alkoxycarbonyl-substituted neo-tanshinlactones and their heterocyclic

  在六甲基二硅肼锂 (LiHMDS) 存在下，邻苯二甲酸酯与 α-羧基呋喃基丙烯酸酯的级联环化 - 内酯化以中等产率提供了新丹参内酯的会聚和半会聚区域选择性合成。该方法还为迄今为止未报道的 6-烷氧基羰基取代的新丹参内酯及其杂环类似物的直接合成提供了途径。基于 Duff 反应和 Furstner 交叉偶联的组合开发了 4-烷基苯酞的新合成方法。
• Selectfluor-Enabled C(sp³)–H Alkoxylation of 3-Methylfuranocoumarins
  作者：Zengxin Qin、Mengfei Zhao、Kaixin Zhang、Masuo Goto、Kuo-Hsiung Lee、Jizhen Li

  DOI：10.1021/acs.joc.1c00776

  日期：2021.6.4

  A facile and metal-free method for the direct C(sp3)–H bond alkoxylation of 3-methylfuranocoumarins with alcohols has been disclosed. Selectfluor enabled the (hetero)benzylic C–H etherification by tuning the reaction temperature and solvent. Various alcohols were compatible in this transformation with suitable yields. The mechanistic studies revealed that the reaction might undergo the double addition

  已经公开了一种简便且无金属的方法，用于3-甲基呋喃香豆素与醇的直接 C(sp 3 )-H 键烷氧基化。Selectfluor 通过调节反应温度和溶剂来实现（杂）苄基 C-H 醚化。各种醇以合适的产率在该转化中相容。机理研究表明，该反应可能经历了醇的双加成过程，以及氟阴离子的离开和氧鎓离子的形成。
• NEO-TANSHINLACTONE AND ANALOGS AS POTENT AND SELECTIVE ANTI-BREAST CANCER AGENTS
  申请人：Lee Kuo-Hsiung

  公开号：US20090118356A1

  公开（公告）日：2009-05-07

  Compounds of Formulas I-II are described, along with methods of using such compounds for the treatment of cancer and pharmaceutical formulations thereof.

  描述了I-II式化合物，以及使用这些化合物治疗癌症和制备制药配方的方法。
• Neo-tanshinlactone and analogs as potent and selective anti-breast cancer agents
  申请人：Lee Kuo-Hsiung

  公开号：US20050250751A1

  公开（公告）日：2005-11-10

  Compounds of Formulas I-II are described, along with methods of using such compounds for the treatment of cancer and pharmeutical formulations thereof.

  本文描述了I-II式化合物，以及使用这些化合物治疗癌症的方法和制药配方。