tert-butyl N-[(1S,2R)-1-methyl-2-phenylcyclopropyl]carbamate | 1613475-50-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl N-[(1S,2R)-1-methyl-2-phenylcyclopropyl]carbamate
• 英文别名: tert-butyl-N-[(1S,2R)-1-methyl-2-phenyl-cyclopropyl]carbamate
• CAS: 1613475-50-5
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: MAIWLJSRITYSJN-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(1S,2R)-1-methyl-2-phenylcyclopropyl]carbamate 、 2-氯-1-(4-甲基哌嗪-1-基)乙酮盐酸盐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以32%的产率得到tert-butyl N-[(1S,2R)-1-methyl-2-phenylcyclopropyl]-N-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]carbamate
  参考文献：
  名称：

  Cyclopropylamine derivatives useful as inhibitors of histone demethylases kdm1a

  摘要：

  本发明涉及一般式(I)的环丙基衍生物，其中A、R1和R2如规范中所定义。本申请还涉及含有这种化合物的药物组合物以及它们在治疗中的应用。

  公开号：

  EP2740474A1
• 作为产物：
  描述：

  ethyl (1S,2R)-1-methyl-2-phenylcyclopropane-1-carboxylate 在 叠氮磷酸二苯酯 、 水 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 19.0h， 生成 tert-butyl N-[(1S,2R)-1-methyl-2-phenylcyclopropyl]carbamate
  参考文献：
  名称：

  Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: A novel class of irreversible inhibitors of histone demethylase KDM1A

  摘要：

  Histone demethylase KDM1A (also known as LSD1) has become an attractive therapeutic target for the treatment of cancer as well as other disorders such as viral infections. We report on the synthesis of compounds derived from the expansion of tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. These compounds, which are substituted on the cyclopropyl core moiety, were evaluated for their ability to inhibit KDM1A in vitro as well as to function in cells by modulating the expression of Gfi-1b, a well recognized KDM1A target gene. The molecules were all found to covalently inhibit KDM1A and to become increasingly selective against human monoamine oxidases MAO A and MAO B through the introduction of bulkier substituents on the cyclopropylamine ring. Structural and biochemical analysis of selected trans isomers showed that the two stereoisomers are endowed with similar inhibitory activities against KDM1A, but form different covalent adducts with the FAD co-enzyme. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.068

文献信息

• [EN] CYCLOPROPYLAMINE DERIVATIVES USEFUL AS INHIBITORS OF HISTONE DEMETHYLASES KDM1A<br/>[FR] DÉRIVÉS DE CYCLOPROPYLAMINE UTILES EN TANT QU'INHIBITEURS DE HISTONE DÉMÉTHYLASES KDM1A
  申请人：ISTITUTO EUROP DI ONCOLOGIA S R L

  公开号：WO2014086790A1

  公开（公告）日：2014-06-12

  (I) The present invention relates to cyclopropyl derivatives of general formula (I), wherein A, R1, and R2 are as defined in the specification. The present application also relates to pharmaceutical compositions containing such compounds and to their use in therapy.

  本发明涉及一般式(I)的环丙基衍生物，其中A、R1和R2如规范中定义。本申请还涉及含有这类化合物的药物组合物以及它们在治疗中的应用。
• CYCLOPROPYLAMINE DERIVATIVES USEFUL AS INHIBITORS OF HISTONE DEMETHYLASES KDM1A
  申请人：INSTITUTO EUROPEO DI ONCOLOGIA S.R.L.

  公开号：US20150315126A1

  公开（公告）日：2015-11-05

  The present invention relates to cyclopropyl derivatives of general formula (I), wherein A, R 1 , and R 2 are as defined in the specification. The present application also relates to pharmaceutical compositions containing such compounds and to their use in therapy.

  本发明涉及一般式(I)的环丙基衍生物，其中A、R1和R2如规范中所定义。本申请还涉及含有这种化合物的药物组合物以及它们在治疗中的使用。
• US9944589B2
  申请人：——

  公开号：US9944589B2

  公开（公告）日：2018-04-17
• Cyclopropylamine derivatives useful as inhibitors of histone demethylases kdm1a
  申请人：Instituto Europeo di Oncologia S.r.l.

  公开号：EP2740474A1

  公开（公告）日：2014-06-11

  The present invention relates to cyclopropyl derivatives of general formula (I), wherein A, R1, and R2 are as defined in the specification. The present application also relates to pharmaceutical compositions containing such compounds and to their use in therapy.

  本发明涉及一般式(I)的环丙基衍生物，其中A、R1和R2如规范中所定义。本申请还涉及含有这种化合物的药物组合物以及它们在治疗中的应用。
• Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: A novel class of irreversible inhibitors of histone demethylase KDM1A
  作者：Paola Vianello、Oronza A. Botrugno、Anna Cappa、Giuseppe Ciossani、Paola Dessanti、Antonello Mai、Andrea Mattevi、Giuseppe Meroni、Saverio Minucci、Florian Thaler、Marcello Tortorici、Paolo Trifiró、Sergio Valente、Manuela Villa、Mario Varasi、Ciro Mercurio

  DOI：10.1016/j.ejmech.2014.08.068

  日期：2014.10

  Histone demethylase KDM1A (also known as LSD1) has become an attractive therapeutic target for the treatment of cancer as well as other disorders such as viral infections. We report on the synthesis of compounds derived from the expansion of tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. These compounds, which are substituted on the cyclopropyl core moiety, were evaluated for their ability to inhibit KDM1A in vitro as well as to function in cells by modulating the expression of Gfi-1b, a well recognized KDM1A target gene. The molecules were all found to covalently inhibit KDM1A and to become increasingly selective against human monoamine oxidases MAO A and MAO B through the introduction of bulkier substituents on the cyclopropylamine ring. Structural and biochemical analysis of selected trans isomers showed that the two stereoisomers are endowed with similar inhibitory activities against KDM1A, but form different covalent adducts with the FAD co-enzyme. (C) 2014 Elsevier Masson SAS. All rights reserved.