4-methyl-17-hydroxy-16,17-dihydro-11,15-dioxacyclopenta[a]phenanthren-12-one | 865071-09-6

• 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: 4-methyl-17-hydroxy-16,17-dihydro-11,15-dioxacyclopenta[a]phenanthren-12-one
• 英文别名: 17-hydroxy-4-methyl-16,17-dihydro-11,15-dioxa-cyclopenta[a]phenanthren-12-one；14-Hydroxy-6-methyl-12,17-dioxatetracyclo[8.7.0.02,7.011,15]heptadeca-1(10),2,4,6,8,11(15)-hexaen-16-one
• CAS: 865071-09-6
• 化学式: C₁₆H₁₂O₄
• 分子量: 268.269
• InChiKey: FTNLPIKTQYIFBN-UHFFFAOYSA-N

物化性质

• 沸点：
  543.7±50.0 °C(predicted)
• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methyl-17-hydroxy-16,17-dihydro-11,15-dioxacyclopenta[a]phenanthren-12-one 在 盐酸 作用下， 以86%的产率得到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：

  5-甲基-1-萘酚 在 potassium carbonate 作用下， 以 水 为溶剂， 反应 5.08h， 生成 4-methyl-17-hydroxy-16,17-dihydro-11,15-dioxacyclopenta[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

• 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。
• 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. 254. Synthesis and Biological Evaluation of Novel Neo-tanshinlactone Analogues as Potent Anti-Breast Cancer Agents
  作者：Xihong Wang、Kyoko Nakagawa-Goto、Kenneth F. Bastow、Ming-Jaw Don、Yun-Lian Lin、Tian-Shung Wu、Kuo-Hsiung Lee

  DOI：10.1021/jm060184d

  日期：2006.9.1

  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.