[[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-(4-{[(4-iodo-phenyl)-methyl-amino]-methyl}-trans-cyclohexyl)-amino]-acetic acid methyl ester | 1313365-98-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-(4-{[(4-iodo-phenyl)-methyl-amino]-methyl}-trans-cyclohexyl)-amino]-acetic acid methyl ester
• 英文别名: [[2-(tert-butoxycarbonylmethylamino)ethyl]-(4-{[(4-iodophenyl)methylamino]methyl}-trans-cyclohexyl)amino]acetic acid methyl ester
• CAS: 1313365-98-8
• 化学式: C₂₅H₄₀IN₃O₄
• 分子量: 573.515
• InChiKey: DUOGRMMHCDVUTF-XYWHTSSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.63
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  62.32
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-(4-{[(4-iodo-phenyl)-methyl-amino]-methyl}-trans-cyclohexyl)-amino]-acetic acid methyl ester 在 盐酸 、 potassium phosphate 、 copper(l) iodide 、 trans-1,2-Diaminocyclohexane 作用下， 以 1,4-二氧六环 为溶剂， 反应 22.5h， 生成 NVP-CGM097
  参考文献：
  名称：

  Crystalline form of an inhibitor of MDM2/4 and p53 interaction

  摘要：

  (S)-1-(4-氯苯基)-7-异丙氧基-6-甲氧基-2-(4-{甲基-[4-(4-甲基-3-氧代-哌嗪-1-基)-反式-环己基甲基]-氨基}-苯基)-1,4-二氢-2H-异喹啉-3-酮的晶体形式，用于治疗与p53或其变体以及MDM2和/或MDM4或其变体之间相互作用相关的疾病或紊乱。

  公开号：

  US20120129871A1
• 作为产物：
  描述：

  {4-[(4-iodo-phenylamino)-methyl]-trans-cyclohexyl}-carbamic acid tert-butyl ester 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 [[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-(4-{[(4-iodo-phenyl)-methyl-amino]-methyl}-trans-cyclohexyl)-amino]-acetic acid methyl ester
  参考文献：
  名称：

  Crystalline form of an inhibitor of MDM2/4 and p53 interaction

  摘要：

  (S)-1-(4-氯苯基)-7-异丙氧基-6-甲氧基-2-(4-{甲基-[4-(4-甲基-3-氧代-哌嗪-1-基)-反式-环己基甲基]-氨基}-苯基)-1,4-二氢-2H-异喹啉-3-酮的晶体形式，用于治疗与p53或其变体以及MDM2和/或MDM4或其变体之间相互作用相关的疾病或紊乱。

  公开号：

  US20120129871A1

文献信息

• Substituted Isoquinolinones and Quinazolinones
  申请人：BERGHAUSEN Joerg

  公开号：US20110230457A1

  公开（公告）日：2011-09-22

  The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) wherein Z is CH 2 or N—R 4 and X, R 1 , R 2 , R 4 , R 6 , R 7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

  这项发明涉及公式（I）中的取代氮含有的双环杂环化合物，其中Z为CH2或N—R4，X、R1、R2、R4、R6、R7和n的定义如描述中所述。这类化合物适用于治疗由MDM2和/或MDM4的活性介导的疾病或疾病变体。
• CRYSTALLINE FORM OF AN INHIBITOR OF MDM2/4 AND P53 INTERACTION
  申请人：Berghausen Joerg

  公开号：US20130245036A1

  公开（公告）日：2013-09-19

  A crystalline form of (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one, which is useful in the treatment of a disease or disorder associated with the interaction between p53, or variants thereof, and MDM2 and/or MDM4, or variants thereof, respectively.

  一种结晶形式的(S)-1-(4-氯苯基)-7-异丙氧基-6-甲氧基-2-(4-甲基-[4-(4-甲基-3-氧代哌嗪-1-基)-反式环己基甲基]-氨基}-苯基)-1,4-二氢-2H-异喹啉-3-酮，用于治疗与p53或其变体以及MDM2和/或MDM4或其变体之间相互作用相关的疾病或紊乱。
• SUBSTITUTED ISOQUINOLINONES AND QUINAZOLINONES
  申请人：Novartis AG

  公开号：US20130281473A1

  公开（公告）日：2013-10-24

  The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) wherein Z is CH 2 or N—R 4 and X, R 1 , R 2 , R 4 , R 6 , R 7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

  本发明涉及式(I)的取代氮含杂环的双环杂环化合物，其中Z是CH2或N-R4，X，R1，R2，R4，R6，R7和n的定义如说明书中所定义。这类化合物适用于治疗由MDM2和/或MDM4的活性或其变异体介导的疾病或疾病。
• Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors
  作者：Philipp Holzer、Keiichi Masuya、Pascal Furet、Joerg Kallen、Therese Valat-Stachyra、Stéphane Ferretti、Joerg Berghausen、Michèle Bouisset-Leonard、Nicole Buschmann、Carole Pissot-Soldermann、Caroline Rynn、Stephan Ruetz、Stefan Stutz、Patrick Chène、Sébastien Jeay、Francois Gessier

  DOI：10.1021/acs.jmedchem.5b00810

  日期：2015.8.27

  As a result of our efforts to discover novel p53:MDM2 protein-protein interaction inhibitors useful for treating cancer, the potent and selective MDM2 inhibitor NVP-CGM097 (1) with an excellent in vivo profile was selected as a clinical candidate and is currently in phase 1 clinical development. This article provides an overview of the discovery of this new clinical p53:MDM2 inhibitor. The following aspects are addressed: mechanism of action, scientific rationale, binding mode, medicinal chemistry, pharmacokinetic and pharmacodynamic properties, and in vivo pharmacology/toxicology in preclinical species.
• US8440693B2
  申请人：——

  公开号：US8440693B2

  公开（公告）日：2013-05-14