(2R,3R,4R,5S)-3-(3-chlorophenyl)-4-(4-chlorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxybutyl)amide | 1219082-06-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (2R,3R,4R,5S)-3-(3-chlorophenyl)-4-(4-chlorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxybutyl)amide
• 英文别名: (2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide；(3r,4r,5s)-3-(3-Chlorophenyl)-4-(4-Chlorophenyl)-4-Cyano-N-[(3s)-3,4-Dihydroxybutyl]-5-(2,2-Dimethylpropyl)-D-Prolinamide；(2R,3R,4R,5S)-3-(3-chlorophenyl)-4-(4-chlorophenyl)-4-cyano-N-[(3S)-3,4-dihydroxybutyl]-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxamide
• CAS: 1219082-06-0
• 化学式: C₂₇H₃₃Cl₂N₃O₃
• 分子量: 518.483
• InChiKey: ZSZGGSIFAMXPIG-CPASSRBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  105
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-[(E)-(3,3-dimethylbutylidene)amino]acetic acid tert-butyl ester 在 silver fluoride 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 37.08h， 生成 (2S,3S,4S,5R)-3-(3-chlorophenyl)-4-(4-chlorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxybutyl)amide 、 (2R,3R,4R,5S)-3-(3-chlorophenyl)-4-(4-chlorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxybutyl)amide
  参考文献：
  名称：

  Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

  摘要：

  Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.

  DOI：

  10.1021/jm400487c

文献信息

• Substituted Pyrrolidine-2-Carboxamides
  申请人：Ding Qingjie

  公开号：US20100075948A1

  公开（公告）日：2010-03-25

  There are provided compounds of the formula wherein X, Y, R 1 , R 2 , R 3 , R 3 , R 4 , R 5 , R 6 and R 7 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

  提供了以下式的化合物 其中X、Y、R1、R2、R3、R3、R4、R5、R6和R7如本文所述，以及其对映体和药用可接受的盐和酯。这些化合物可用作抗癌药物。
• SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2340021A1

  公开（公告）日：2011-07-06
• US8354444B2
  申请人：——

  公开号：US8354444B2

  公开（公告）日：2013-01-15
• [EN] SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES<br/>[FR] PYRROLIDINE-2-CARBOXAMIDES SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011098398A1

  公开（公告）日：2011-08-18

  There are provided compounds of the formula (I) wherein X, Y, R1, R2, R3, R3, R4, R5, R6 and R7 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.
• Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development
  作者：Qingjie Ding、Zhuming Zhang、Jin-Jun Liu、Nan Jiang、Jing Zhang、Tina M. Ross、Xin-Jie Chu、David Bartkovitz、Frank Podlaski、Cheryl Janson、Christian Tovar、Zoran M. Filipovic、Brian Higgins、Kelli Glenn、Kathryn Packman、Lyubomir T. Vassilev、Bradford Graves

  DOI：10.1021/jm400487c

  日期：2013.7.25

  Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.