ethyl 2-diethoxyphosphoryl-3-(2-naphthyl)propanoate | 1613475-20-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 2-diethoxyphosphoryl-3-(2-naphthyl)propanoate
• 英文别名: Ethyl 2-diethoxyphosphoryl-3-naphthalen-2-ylpropanoate；ethyl 2-diethoxyphosphoryl-3-naphthalen-2-ylpropanoate
• CAS: 1613475-20-9
• 化学式: C₁₉H₂₅O₅P
• 分子量: 364.378
• InChiKey: XARGPWDZNOMAPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-diethoxyphosphoryl-3-(2-naphthyl)propanoate 在 正丁基锂 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 2.91h， 生成
  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
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 、 2-(氯甲基)萘 在 sodium hydride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 4.67h， 以50%的产率得到ethyl 2-diethoxyphosphoryl-3-(2-naphthyl)propanoate
  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

文献信息

• Catalytic Synthesis of 8‐Membered Ring Compounds via Cobalt(III)‐Carbene Radicals
  作者：Minghui Zhou、Marianne Lankelma、Jarl Ivar Vlugt、Bas Bruin

  DOI：10.1002/anie.202002674

  日期：2020.6.26

  The metalloradical activation of o ‐aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)‐carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium‐sized ring structures. Herein we make use of the intrinsic radical‐type reactivity of cobalt(III)‐carbene radical intermediates in the [CoII(TPP)]‐catalyzed (TPP=tetraphenylporphyrin)

  用甲苯磺酰肼和钴（II）卟啉催化剂对邻芳基醛进行金属自由基活化，产生钴（III）卡宾自由基中间体，为合成中等大小的环结构提供了一种新的强大策略。在此，我们利用钴(III)-卡宾自由基中间体的固有自由基型反应活性，在[Co II (TPP)]催化（TPP=四苯基卟啉）合成两种类型的8元环化合物；新型二苯并环辛烯和前所未有的单苯并环辛二烯。该方法已成功应用，以良好的收率和优异的取代基耐受性提供了多种八元环化合物。密度泛函理论（DFT）计算和实验结果表明，反应通过氢原子从双烯丙基/苯甲基烯丙基CH键转移到卡宾自由基进行，然后通过两个不同的过程进行闭环，形成两种不同类型的碳烯。 8元环产物。虽然二苯并环辛烯很可能是由邻醌二甲烷 ( o -QDM) 解离形成的，经过非催化 8π 环化，DFT 计算表明单苯并环辛二烯的闭环涉及钴配位层中的自由基反弹步骤。后一种机制意味着手性单苯并环辛二烯前所未有的对映
• [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。
• Further insights into the SAR of α-substituted cyclopropylamine derivatives as inhibitors of histone demethylase KDM1A
  作者：Marco Pieroni、Giannamaria Annunziato、Elisa Azzali、Paola Dessanti、Ciro Mercurio、Giuseppe Meroni、Paolo Trifiró、Paola Vianello、Manuela Villa、Claudia Beato、Mario Varasi、Gabriele Costantino

  DOI：10.1016/j.ejmech.2014.12.032

  日期：2015.3

  including histone methylation and acetylation, and DNA methylation, are thought to play important roles in the onset and progression of cancer in numerous tumour cell lines. Lysine-specific demethylase 1 (LSD1 or KDM1A) is highly expressed in different cancer types and inhibiting KDM1A activity seems to have high therapeutic potential in cancer treatment. In the recent years, several inhibitors of KDM1A

  表观遗传学的改变，包括组蛋白甲基化和乙酰化，以及DNA甲基化，被认为在许多肿瘤细胞系的癌症的发生和发展中起着重要的作用。赖氨酸特异性脱甲基酶1（LSD1或KDM1A）在不同类型的癌症中高度表达，抑制KDM1A活性似乎在癌症治疗中具有很高的治疗潜力。 近年来，已经制备并公开了几种KDM1A抑制剂。这些衍生物中的大多数是基于反式环丙胺的结构设计的，因为环丙烷核心负责抑制剂与KDM蛋白催化结构域之间的共价相互作用。在这项研究中，我们进一步扩展了关于化合物1a – e的SAR ，最近发现它们可抑制KDM1A并具有良好的活性。如化合物44a所示，在带有少量官能团的环丙烷环的β位置修饰苯环，这些官能团大多被卤化，尤其是在间位，导致对KDM1A的抑制活性显着提高。，其效力在低纳摩尔范围（31 nM）中。
• 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