2-[(氯乙酰基)(3-氯-4-甲氧基苯基)氨基]-N-(2-苯乙基)-2-噻吩-2-基乙酰胺 | 1035072-16-2

• 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
• 中文名称: 2-[(氯乙酰基)(3-氯-4-甲氧基苯基)氨基]-N-(2-苯乙基)-2-噻吩-2-基乙酰胺
• 英文名称: 2-chloro-N-(3-chloro-4-methoxyphenyl)-N-(2-oxo-2-(phenethylamino)-1-(thiophen-2-yl)ethyl)acetamide
• 英文别名: ML 162；ML162；2-[(chloroacetyl)(3-chloro-4-methoxyphenyl)amino]-N-(2-phenylethyl)-2-thien-2-ylacetamide；2-(3-chloro-N-(2-chloroacetyl)-4-methoxyanilino)-N-(2-phenylethyl)-2-thiophen-2-ylacetamide
• CAS: 1035072-16-2
• 化学式: C₂₃H₂₂Cl₂N₂O₃S
• 分子量: 477.411
• InChiKey: UNVKYJSNMVDZJE-UHFFFAOYSA-N

物化性质

• 沸点：
  699.3±55.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)
• 溶解度：
  DMF:10.0(最大浓度 mg/mL);20.95(最大浓度 mM)DMSO:25.0(最大浓度 mg/mL);52.37(最大浓度 mM)乙醇:1.0(最大浓度 mg/mL);2.09(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-噻吩甲醛 、 苯乙基乙腈 、 氯乙酸 、 3-氯-4-甲氧基苯胺 以 甲醇 为溶剂， 反应 48.0h， 以59%的产率得到2-[(氯乙酰基)(3-氯-4-甲氧基苯基)氨基]-N-(2-苯乙基)-2-噻吩-2-基乙酰胺
  参考文献：
  名称：

  Development of small-molecule probes that selectively kill cells induced to express mutant RAS

  摘要：

  Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRAS(G12V) followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRAS(G12V) oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML162 and CID 49766530, ML210) with nanomolar potencies and 4-23-fold selectivities, which can potentially be used for identifying oncogene-specific pathways and targets in cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.047

文献信息

• QUINAZOLINONE-BASED ONCOGENIC-RAS-SELECTIVE LETHAL COMPOUNDS AND THEIR USE
  申请人：THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

  公开号：US20150175558A1

  公开（公告）日：2015-06-25

  The present invention provides, inter alia, compounds having the structure (1) compositions containing such compounds are also provided. Methods for using such compounds or compositions for treating or ameliorating the effects of a cancer having a cell that harbors an oncogenic RAS mutation, for modulating a lipoxygenase in a ferroptosis cell death pathway, and for depleting reduced glutathione (GSH) in a cell harboring an oncogenic RAS mutation are further provided.

  本发明提供了结构为（1）的化合物，还提供了含有这种化合物的组合物。还提供了使用这种化合物或组合物治疗或改善携带致癌RAS突变细胞的癌症的影响，调节铁死亡细胞途径中的脂氧合酶，以及耗竭携带致癌RAS突变细胞的还原型谷胱甘肽（GSH）的方法。
• [EN] GPX4 PROTEIN DEGRADATION-INDUCING COMPOUND<br/>[FR] COMPOSÉ INDUISANT LA DÉGRADATION DE LA PROTÉINE GPX4<br/>[KO] GPX4 단백질 분해 유도 화합물
  申请人：UPPTHERA

  公开号：WO2022119362A1

  公开（公告）日：2022-06-09

  본 발명은 GPX4 단백질 분해 유도 화합물에 관한 것이다. 구체적으로, 본 발명은 GPX4 단백질 결합 모이어티와 CRBN E3 유비퀴틴 라이게이즈 결합 모이어티가 화학적 링커로 연결된 이기능성 화합물, 이의 제조방법, 이를 활용한 GPX4 단백질의 분해 방법 및 GPX4 관련 질환 또는 페롭토시스 관련 질환의 예방 또는 치료 용도 등을 제공한다.

  这项发明涉及GPX4蛋白质降解诱导化合物。具体而言，本发明提供了一种将GPX4蛋白质结合模因子和CRBN E3泛素连接酶结合模因子通过化学连接剂连接的这种功能化合物、其制备方法、利用其分解GPX4蛋白质的方法以及预防或治疗与GPX4相关疾病或过氧化脂质症相关疾病的用途等。
• Combination cancer therapy with pentaaza macrocyclic ring complex and ascorbate compound
  申请人：Galera Labs, LLC

  公开号：US11219614B2

  公开（公告）日：2022-01-11

  A method of treating cancer in a subject includes administering an active agent selected from ascorbic acid, an ascorbic acid derivative, and/or a pharmaceutically acceptable salt thereof and administering a pentaaza macrocyclic ring complex corresponding to formula (I) below:

  一种治疗受试者癌症的方法包括施用选自抗坏血酸、抗坏血酸衍生物和/或其药学上可接受的盐的活性剂，以及施用与下式（I）相对应的五氮杂大环环络合物：
• COMBINATION THERAPY FOR CANCER TREATMENT
  申请人：Galera Labs, LLC

  公开号：US20190151331A1

  公开（公告）日：2019-05-23

  A method of treating cancer in a subject includes administering at least one active agent including one or more of a thioredoxin reductase inhibitor and a glutathione depleting agent, and administering a pentaaza macrocyclic ring complex corresponding to formula (I) below:
• COMBINATION CANCER THERAPY WITH PENTAAZA MACROCYCLIC RING COMPLEX AND ASCORBATE COMPOUND
  申请人：Galera Labs, LLC

  公开号：US20190209524A1

  公开（公告）日：2019-07-11

  A method of treating cancer in a subject includes administering an active agent selected from ascorbic acid, an ascorbic acid derivative, and/or a pharmaceutically acceptable salt thereof and administering a pentaaza macrocyclic ring complex corresponding to formula (I) below: