4-羟基-7-甲基-2H-苯并[h]苯并吡喃-2-酮 | 802910-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 中文名称: 4-羟基-7-甲基-2H-苯并[h]苯并吡喃-2-酮
• 中文别名: (4aS,4bR,6R,6aR,10aS,10bR,12aS)-8-甲酰基-1,1,4a,6a,10b-五甲基-1,2,3,4,4a,4b,5,6,6a,7,10,10a,10b,11,12,12a-十六氢屈-6-基乙酸酯
• 英文名称: 4-hydroxy-7-methyl-benzo[h]chromen-2-one
• 英文别名: 4-hydroxy-7-methylbenzo[h]chromen-2-one
• CAS: 802910-33-4
• 化学式: C₁₄H₁₀O₃
• 分子量: 226.232
• InChiKey: ZJXYANHJIKSKLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-羟基-7-甲基-2H-苯并[h]苯并吡喃-2-酮 在 盐酸 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 5.08h， 生成 4-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
• 作为产物：
  描述：

  1,2-dihydro-4-methyl-8-methoxynaphthalene 在 palladium on activated charcoal 三溴化硼 作用下， 以 三甘醇二甲醚 、 二氯甲烷 为溶剂， 反应 78.0h， 生成 4-羟基-7-甲基-2H-苯并[h]苯并吡喃-2-酮
  参考文献：
  名称：

  Antitumor Agents. 239. Isolation, Structure Elucidation, Total Synthesis, and Anti-Breast Cancer Activity of Neo-tanshinlactone from Salvia miltiorrhiza

  摘要：

  Neo-tanshinlactone (1) was isolated and synthesized for the first time and evaluated in vitro against several human cancer cell lines. Compound 1 showed significant inhibition against two ER+ human breast cancer cell lines and was 10-fold more potent and 20-fold more selective as compared to tamoxifen citrate. Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer cell line. Therefore, this novel compound merits further development as an anti-breast cancer drug candidate.

  DOI：

  10.1021/jm040112r

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。
• 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。
• Antitumor Agents. 272. Structure−Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues
  作者：Yizhou Dong、Qian Shi、Huei-Chen Pai、Chieh-Yu Peng、Shiow-Lin Pan、Che-Ming Teng、Kyoko Nakagawa-Goto、Donglei Yu、Yi-Nan Liu、Pei-Chi Wu、Kenneth F. Bastow、Susan L. Morris-Natschke、Arnold Brossi、Jing-Yu Lang、Jennifer L. Hsu、Mien-Chie Hung、Eva Y.-H. P. Lee、Kuo-Hsiung Lee

  DOI：10.1021/jm1000858

  日期：2010.3.11

  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.
• Isolation, Structure Elucidation, and Syntheses of Isoneocryptotanshinone II and Tanshinlactone A from Salvia miltiorrhiza
  作者：Ming-Jaw Don、Chang-Ming Sun、Tsung-Mei Chin、Yun-Lian Lin、Chien-Jui Chen、Wei-Chou Chen、Tian-Shung Wu

  DOI：10.3987/com-05-10591

  日期：——