2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid | 1357107-99-3

• 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: 2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid
• CAS: 1357107-99-3
• 化学式: C₂₄H₂₅NO₂
• 分子量: 359.468
• InChiKey: JXIGVUPYYZGRRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid 在 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 正庚烷 为溶剂， 生成 (S)-2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid 、 (R)-2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid
  参考文献：
  名称：

  Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity

  摘要：

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

  DOI：

  10.1021/jm201195m
• 作为产物：
  描述：

  3-甲基二苯甲酮 在 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 硫酸 、 palladium 10% on activated carbon 、 双氧水 、 甲酸铵 、 戴斯-马丁氧化剂 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 二乙二醇二甲醚 、 水 为溶剂， 生成 2-amino-5-(3-methylphenyl)-5,5-diphenylpentanoic acid
  参考文献：
  名称：

  Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity

  摘要：

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

  DOI：

  10.1021/jm201195m