(trans-4-amino-cyclohexylmethyl)-(4-iodo-phenyl)-methyl-amine | 1313365-95-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (trans-4-amino-cyclohexylmethyl)-(4-iodo-phenyl)-methyl-amine
• 英文别名: (trans-4-aminocyclohexylmethyl)(4-iodophenyl)methylamine
• CAS: 1313365-95-5
• 化学式: C₁₄H₂₁IN₂
• 分子量: 344.239
• InChiKey: DTOOJINRJFWYJV-AULYBMBSSA-N

物化性质

• 沸点：
  404.9±20.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  29.26
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (trans-4-amino-cyclohexylmethyl)-(4-iodo-phenyl)-methyl-amine 在 盐酸 、 potassium phosphate 、 copper(l) iodide 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 trans-1,2-cyclohexanediamine 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 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：

  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。

  公开号：

  US20130245036A1
• 作为产物：
  描述：

  对碘苯胺 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 (trans-4-amino-cyclohexylmethyl)-(4-iodo-phenyl)-methyl-amine
  参考文献：
  名称：

  CRYSTALLINE FORM OF AN INHIBITOR OF MDM2/4 AND P53 INTERACTION

  摘要：

  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。

  公开号：

  US20130245036A1

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：US20120129871A1

  公开（公告）日：2012-05-24

  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,

  (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。
• 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。
• MDM2 protein degraders
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US11192898B2

  公开（公告）日：2021-12-07

  The present disclosure provides compounds represented by Formula I-A: A1-L1-B1 I-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.

  本公开提供了由式I-A代表的化合物：A1-L1-B1 I-A及其药学上可接受的盐、水合物和溶液，其中A1、B1和L1如说明书中所定义。本公开还提供了式 I-A 的化合物，用于治疗对 MDM2 蛋白降解有反应的病症或紊乱，如癌症。
• 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.