(±)-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-4-fluoro-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetic acid salt

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (±)-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-4-fluoro-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetic acid salt
• 英文别名: rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-4-fluoro-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetate；(2'R,3R,3'S,5'S)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-4-fluoro-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxylic acid;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₃H₂₂Cl₂F₂N₂O₃
• 分子量: 597.366
• InChiKey: OOHUEPBOBFOAIN-ROQBSYDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (±)-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-4-fluoro-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetic acid salt 在 二氧化碳 、 双氧水 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 二苯基次膦酰氯 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 35.0 ℃ 、10.0 MPa 条件下， 反应 21.5h， 生成 (±)-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-4-fluoro-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-methoxyphenyl)amide
  参考文献：
  名称：

  Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy

  摘要：

  The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.05.072
• 作为产物：
  描述：

  3,3-二甲基丁醛 在 silver fluoride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 40.0h， 生成 (±)-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-4-fluoro-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetic acid salt
  参考文献：
  名称：

  SPIROINDOLINONE PYRROLIDINES

  摘要：

  提供了以下式中的化合物，其中X、Y和R1至R8如本文所述，以及其对映体、药用可接受的盐和酯。这些化合物可用作抗癌药物。

  公开号：

  US20110130398A1

文献信息

• SPIROINDOLINONE PYRROLIDINES
  申请人：Bartkovitz David Joseph

  公开号：US20110130398A1

  公开（公告）日：2011-06-02

  There are provided compounds of the formula wherein X, Y and R 1 to R 8 are described herein along with the enantiomers, pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

  提供了以下式中的化合物，其中X、Y和R1至R8如本文所述，以及其对映体、药用可接受的盐和酯。这些化合物可用作抗癌药物。
• US8088815B2
  申请人：——

  公开号：US8088815B2

  公开（公告）日：2012-01-03
• Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy
  作者：Zhuming Zhang、Qingjie Ding、Jin-Jun Liu、Jing Zhang、Nan Jiang、Xin-Jie Chu、David Bartkovitz、Kin-Chun Luk、Cheryl Janson、Christian Tovar、Zoran M. Filipovic、Brian Higgins、Kelli Glenn、Kathryn Packman、Lyubomir T. Vassilev、Bradford Graves

  DOI：10.1016/j.bmc.2014.05.072

  日期：2014.8

  The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994. (C) 2014 Elsevier Ltd. All rights reserved.