(R)-1-(phenylthio)-4-(piperidin-1-yl)butan-2-amine | 1402141-77-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (R)-1-(phenylthio)-4-(piperidin-1-yl)butan-2-amine
• 英文别名: (2R)-1-phenylsulfanyl-4-piperidin-1-ylbutan-2-amine
• CAS: 1402141-77-8
• 化学式: C₁₅H₂₄N₂S
• 分子量: 264.435
• InChiKey: YPIDRCABFZJVPH-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-(phenylthio)-4-(piperidin-1-yl)butan-2-amine 、 5-(4-chlorophenyl)-4-(3-(4-(4-(4-fluoro-3-(trifluoromethylsulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)-phenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylic acid 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-5-(4-chlorophenyl)-1,2-dimethyl-4-(3-(4-(4-(4-(1-(phenylthio)-4-(piperidin-1-yl)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)-phenyl)-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

  摘要：

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.

  DOI：

  10.1021/jm3010306
• 作为产物：
  描述：

  (R)-N-Fmoc-3-氨基-4-(苯硫基)丁酸 在 硼烷四氢呋喃络合物 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 19.0h， 生成 (R)-1-(phenylthio)-4-(piperidin-1-yl)butan-2-amine
  参考文献：
  名称：

  Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

  摘要：

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.

  DOI：

  10.1021/jm3010306

文献信息

• Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression
  作者：Jianfang Chen、Haibin Zhou、Angelo Aguilar、Liu Liu、Longchuan Bai、Donna McEachern、Chao-Yie Yang、Jennifer L. Meagher、Jeanne A. Stuckey、Shaomeng Wang

  DOI：10.1021/jm3010306

  日期：2012.10.11

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.