(R,R)-1,1', 6,6',7,7'-hexamethoxy-3,3'-dimethyl-N5,N5'-bis(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamide | 1228108-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (R,R)-1,1', 6,6',7,7'-hexamethoxy-3,3'-dimethyl-N5,N5'-bis(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamide
• 英文别名: 2,3,5-trimethoxy-7-methyl-N-[(2R)-2-phenylpropyl]-6-[1,6,7-trimethoxy-3-methyl-5-[[(2R)-2-phenylpropyl]carbamoyl]naphthalen-2-yl]naphthalene-1-carboxamide
• CAS: 1228108-63-1
• 化学式: C₄₈H₅₂N₂O₈
• 分子量: 784.949
• InChiKey: PHFDHUKXYVHMBJ-KYJUHHDHSA-N

物化性质

• 沸点：
  835.5±65.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  58
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R,R)-1,1', 6,6',7,7'-hexamethoxy-3,3'-dimethyl-N5,N5'-bis(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamide 在 三溴化硼 、 盐酸 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以25 mg的产率得到sabutoclax
  参考文献：
  名称：

  BI-97C1, an Optically Pure Apogossypol Derivative as Pan-Active Inhibitor of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins

  摘要：

  In our continued attempts to identify novel and effective pan-Bcl-2 antagonists, we have recently reported a series of compound 2 (Apogossypol) derivatives, resulting in the chiral compound 4 (8r). We report here the synthesis and evaluation on its optically pure individual isomers. Compound 11 (BI-97Cl), the most potent diastereoisomer of compound 4, inhibits the binding of BH3 peptides to Bcl-X(L), Bcl-2, Mcl-l, and Bfl-l with IC(50) values of 0.31, 0.32, 0.20, and 0.62 mu M, respectively. The compound also potently inhibits cell growth of human prostate cancer, lung cancer, and lymphoma cell lines with EC(50) values of 0.13, 0.56, and 0.049 mu M, respectively, and shows little cytotoxicity against bax(-/-)bak(-/-) cells. Compound 11 displays in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, compound 11 represents a potential drug lead for the development of novel apoptosis-based therapies against cancer.

  DOI：

  10.1021/jm1001265
• 作为产物：
  描述：

  1,1',6,6',7,7'-hexamethoxy-3,3'-dimethyl-2,2'-binaphthalene-5,5'-dicarboxylic acid 、 (R)-2-苯基-1-丙胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.25h， 以76%的产率得到(R,R)-1,1', 6,6',7,7'-hexamethoxy-3,3'-dimethyl-N5,N5'-bis(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamide
  参考文献：
  名称：

  BI-97C1, an Optically Pure Apogossypol Derivative as Pan-Active Inhibitor of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins

  摘要：

  In our continued attempts to identify novel and effective pan-Bcl-2 antagonists, we have recently reported a series of compound 2 (Apogossypol) derivatives, resulting in the chiral compound 4 (8r). We report here the synthesis and evaluation on its optically pure individual isomers. Compound 11 (BI-97Cl), the most potent diastereoisomer of compound 4, inhibits the binding of BH3 peptides to Bcl-X(L), Bcl-2, Mcl-l, and Bfl-l with IC(50) values of 0.31, 0.32, 0.20, and 0.62 mu M, respectively. The compound also potently inhibits cell growth of human prostate cancer, lung cancer, and lymphoma cell lines with EC(50) values of 0.13, 0.56, and 0.049 mu M, respectively, and shows little cytotoxicity against bax(-/-)bak(-/-) cells. Compound 11 displays in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, compound 11 represents a potential drug lead for the development of novel apoptosis-based therapies against cancer.

  DOI：

  10.1021/jm1001265

文献信息

• BI-97C1, an Optically Pure Apogossypol Derivative as Pan-Active Inhibitor of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins
  作者：Jun Wei、John L. Stebbins、Shinichi Kitada、Rupesh Dash、William Placzek、Michele F. Rega、Bainan Wu、Jason Cellitti、Dayong Zhai、Li Yang、Russell Dahl、Paul B. Fisher、John C. Reed、Maurizio Pellecchia

  DOI：10.1021/jm1001265

  日期：2010.5.27

  In our continued attempts to identify novel and effective pan-Bcl-2 antagonists, we have recently reported a series of compound 2 (Apogossypol) derivatives, resulting in the chiral compound 4 (8r). We report here the synthesis and evaluation on its optically pure individual isomers. Compound 11 (BI-97Cl), the most potent diastereoisomer of compound 4, inhibits the binding of BH3 peptides to Bcl-X(L), Bcl-2, Mcl-l, and Bfl-l with IC(50) values of 0.31, 0.32, 0.20, and 0.62 mu M, respectively. The compound also potently inhibits cell growth of human prostate cancer, lung cancer, and lymphoma cell lines with EC(50) values of 0.13, 0.56, and 0.049 mu M, respectively, and shows little cytotoxicity against bax(-/-)bak(-/-) cells. Compound 11 displays in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, compound 11 represents a potential drug lead for the development of novel apoptosis-based therapies against cancer.