3-[2-Aminoethylsulfanyl-(4-methylphenyl)-phenylmethyl]benzonitrile | 1426165-30-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3-[2-Aminoethylsulfanyl-(4-methylphenyl)-phenylmethyl]benzonitrile
• 英文别名: 3-[2-aminoethylsulfanyl-(4-methylphenyl)-phenylmethyl]benzonitrile
• CAS: 1426165-30-1
• 化学式: C₂₃H₂₂N₂S
• 分子量: 358.507
• InChiKey: JCHGXYLXAIPILQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-甲基二苯甲酮 在 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 24.4h， 生成 3-[2-Aminoethylsulfanyl-(4-methylphenyl)-phenylmethyl]benzonitrile
  参考文献：
  名称：

  Optimized S-Trityl-l-cysteine-Based Inhibitors of Kinesin Spindle Protein with Potent in Vivo Antitumor Activity in Lung Cancer Xenograft Models

  摘要：

  The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-L-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activity. We report here their further optimization to produce extremely potent inhibitors of Eg5 (K-i(app) < 10 nM) with broad-spectrum activity against cancer cell lines comparable to the Phase II drug candidates ispinesib and SB-743921. They have good oral bioavailability and pharmacolcinetics and induced complete tumor regression in nude mice explanted with lung cancer patient xenografts. Furthermore, they display fewer liabilities with CYP-metabolizing enzymes and hERG compared with ispinesib and SB-743921, which is important given the likely application of Eg5 inhibitors in combination therapies. We present the case for this preclinical series to be investigated in single and combination chemotherapies, especially targeting hematological malignancies.

  DOI：

  10.1021/jm3014597

文献信息

• Optimized <i>S</i>-Trityl-<scp>l</scp>-cysteine-Based Inhibitors of Kinesin Spindle Protein with Potent in Vivo Antitumor Activity in Lung Cancer Xenograft Models
  作者：James A. D. Good、Fang Wang、Oliver Rath、Hung Yi Kristal Kaan、Sandeep K. Talapatra、Dawid Podgórski、Simon P. MacKay、Frank Kozielski

  DOI：10.1021/jm3014597

  日期：2013.3.14

  The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-L-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activity. We report here their further optimization to produce extremely potent inhibitors of Eg5 (K-i(app) < 10 nM) with broad-spectrum activity against cancer cell lines comparable to the Phase II drug candidates ispinesib and SB-743921. They have good oral bioavailability and pharmacolcinetics and induced complete tumor regression in nude mice explanted with lung cancer patient xenografts. Furthermore, they display fewer liabilities with CYP-metabolizing enzymes and hERG compared with ispinesib and SB-743921, which is important given the likely application of Eg5 inhibitors in combination therapies. We present the case for this preclinical series to be investigated in single and combination chemotherapies, especially targeting hematological malignancies.