1-methyl-11H-benzo[h]furo[3,2-c]chromene-11-thione | 1211519-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 1-methyl-11H-benzo[h]furo[3,2-c]chromene-11-thione
• 英文别名: 1-Methyl-11H-furo[2,3-d]naphtho[1,2-b]pyran-11-thione；14-methyl-12,17-dioxatetracyclo[8.7.0.02,7.011,15]heptadeca-1(10),2,4,6,8,11(15),13-heptaene-16-thione
• CAS: 1211519-00-4
• 化学式: C₁₆H₁₀O₂S
• 分子量: 266.32
• InChiKey: PLPVNSAGRZWATA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 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：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  17-methyl-11,15-dioxa-cyclopenta[a]phenanthren-12-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 7.0h， 以90%的产率得到1-methyl-11H-benzo[h]furo[3,2-c]chromene-11-thione
  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

文献信息

• 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。
• US7495026B2
  申请人：——

  公开号：US7495026B2

  公开（公告）日：2009-02-24
• US7795299B2
  申请人：——

  公开号：US7795299B2

  公开（公告）日：2010-09-14
• 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.