4-[(4'-aminophenyl)amino]-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one | 1357161-72-8

• 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: 4-[(4'-aminophenyl)amino]-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one
• 英文别名: 4-(4-Aminoanilino)-7,8,9,10-tetrahydrobenzo[h]chromen-2-one
• CAS: 1357161-72-8
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: YDEFIHKAJYXSPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(4'-aminophenyl)amino]-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 4-[(4'-aminophenyl)amino]-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one hydrochloride
  参考文献：
  名称：

  Antitumor Agents. 289. Design, Synthesis, and Anti-Breast Cancer Activity in Vivo of 4-Amino-2H-benzo[h]chromen-2-one and 4-Amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one Analogues with Improved Water Solubility

  摘要：

  Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues, with IC50 values of 0.038-0.085 mu M in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4[(4'-methoxyphenyl)amino]-2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells, as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and a mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate.

  DOI：

  10.1021/np2007878
• 作为产物：
  描述：

  4-chloro-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one 、 对苯二胺 以 乙醇 为溶剂， 生成 4-[(4'-aminophenyl)amino]-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one
  参考文献：
  名称：

  Antitumor Agents. 289. Design, Synthesis, and Anti-Breast Cancer Activity in Vivo of 4-Amino-2H-benzo[h]chromen-2-one and 4-Amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one Analogues with Improved Water Solubility

  摘要：

  Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues, with IC50 values of 0.038-0.085 mu M in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4[(4'-methoxyphenyl)amino]-2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells, as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and a mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate.

  DOI：

  10.1021/np2007878

文献信息

• Antitumor Agents. 289. Design, Synthesis, and Anti-Breast Cancer Activity in Vivo of 4-Amino-2<i>H</i>-benzo[<i>h</i>]chromen-2-one and 4-Amino-7,8,9,10-tetrahydro-2<i>H</i>-benzo[<i>h</i>]chromen-2-one Analogues with Improved Water Solubility
  作者：Yizhou Dong、Kyoko Nakagawa-Goto、Chin-Yu Lai、Susan L. Morris-Natschke、Kenneth F. Bastow、Yoon Kim、Eva Y.-H. P. Lee、Kuo-Hsiung Lee

  DOI：10.1021/np2007878

  日期：2012.3.23

  Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues, with IC50 values of 0.038-0.085 mu M in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4[(4'-methoxyphenyl)amino]-2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells, as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and a mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate.