HA 14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: HA 14-1
• 英文别名: ethyl (4R)-2-amino-6-bromo-4-[(1S)-1-cyano-2-ethoxy-2-oxoethyl]-4H-chromene-3-carboxylate
• 化学式: C₁₇H₁₇BrN₂O₅
• 分子量: 409.236
• InChiKey: SXJDCULZDFWMJC-YPMHNXCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氰乙酸乙酯 、 5-溴水杨醛 在 二乙胺 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以93%的产率得到HA 14-1
  参考文献：
  名称：

  Diethylamine: A smart organocatalyst in eco-safe and diastereoselective synthesis of medicinally privileged 2-amino-4H-chromenes at ambient temperature

  摘要：

  摘要 二乙胺已被证明是一个高效的有机催化剂，能够以一次性缩合法选择性合成Bcl-2蛋白拮抗剂（HA-14-1）及其结构类似物，该方法通过水杨醛与三种不同的C–H酸（即乙基氰乙酸酯、苯基磺酰乙腈和丙二腈）反应实现。该催化剂在商业上的易得性和极低的成本，以及避免传统的后处理和纯化程序，使这一可扩展的方案符合“近乎理想合成”的标准。 补充材料： 本文的补充材料作为单独文件提供： mmc1.docx

  DOI：

  10.1016/j.crci.2013.02.016

文献信息

• Mesoporous niobiosilicate NbMCF modified with alkali metals in the synthesis of chromene derivatives
  作者：Agata Smuszkiewicz、Jesús Lopez-Sanz、Izabela Sobczak、Maria Ziolek、Rosa M. Martín-Aranda、Elena Soriano、Elena Pérez-Mayoral

  DOI：10.1016/j.cattod.2016.02.042

  日期：2016.11

  alkaline metals) were tested in the reaction of 2-hydroxybenzaldehyde and ethyl cyanoacetate, under solvent-free conditions, at room temperature, leading to mixtures of the corresponding chromenes 4 and 5, as mixtures of diastereomers erythro/threo, in a 2:1 ratio, respectively, with good to excellent yields. Our experimental results indicate that the metal loading on the catalysts and the acid-base character

  我们报告了基于铌介孔泡沫 (NbMCF)、碱金属元素改性的新型催化剂系列的合成、表征和活性。这些材料表现出非常不同的酸碱性质，这归因于用于制备催化剂的 Nb 源以及不同碱金属的存在和负载。Me/NbMCF 材料（其中 Me 是碱金属）在 2-羟基苯甲醛和氰基乙酸乙酯的反应中进行测试，在无溶剂条件下，在室温下，产生相应色烯 4 和 5 的混合物，作为非对映异构体的混合物赤型/苏型，比例分别为 2:1，产率良好至极好。我们的实验结果表明，催化剂上的金属负载量和酸碱特性，质地参数可能是反应性和观察到的非对映选择性的决定因素。计算研究表明，Me/NbMCF 催化剂上碱性氧化物的存在，表现出强碱性，激活了亲核物质（相应的烯醇化物）的形成，并引发了反应。然而，阳离子尺寸对反应物配合物的稳定性有很大的影响，因此较大的中心的存在可能会阻碍有效的醛缩合。
• Combination therapies using agents that target tumor-associated stroma or tumor cells and other pathways
  申请人：BIOMED VALLEY DISCOVERIES, INC.

  公开号：US10758526B2

  公开（公告）日：2020-09-01

  The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a molecularly targeted agent; and (b) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody contains: (i) a heavy chain variable region (VH), which includes an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:7; and (ii) a light chain variable region (VL), which includes an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

  本发明特别提供了治疗或改善疾病（如癌症）对受试者影响的方法。这些方法包括：向有需要的受试者施用(a)治疗有效量的分子靶向制剂；和(b)治疗有效量的单克隆抗体或其抗原结合片段，其中单克隆抗体包含：(i) 重链可变区（VH），其包括选自 SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5 和 SEQ ID NO:7 的氨基酸序列；以及 (ii) 轻链可变区（VL），其包括选自 SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6 和 SEQ ID NO:8 的氨基酸序列。本文还提供了用于治疗癌症等疾病的组合物（包括药物组合物）和试剂盒。
• COMBINATION THERAPIES USING AGENTS THAT TARGET TUMOR-ASSOCIATED STROMA OR TUMOR CELLS AND OTHER PATHWAYS
  申请人：BIOMED VALLEY DISCOVERIES, INC.

  公开号：US20170095575A1

  公开（公告）日：2017-04-06

  The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a molecularly targeted agent; and (b) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody contains: (i) a heavy chain variable region (VH), which includes an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and SEQ ID NO:7; and (ii) a light chain variable region (VL), which includes an amino acid sequence selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and SEQ ID NO:8. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.
• COMBINATION OF A BCL-2 INHIBITOR AND A BROMODOMAIN INHIBITOR FOR TREATING CANCER
  申请人：Gilead Sciences, Inc.

  公开号：US20180133212A1

  公开（公告）日：2018-05-17

  Provided herein are methods and compositions for the treatment of cancer. In particular, the methods include administration of a Bcl-2 inhibitor and a BET inhibitor.
• [EN] CANCER TREATMENTS USING ERK1/2 AND BCL-2 FAMILY INHIBITORS<br/>[FR] TRAITEMENTS DU CANCER FAISANT APPEL À DES INHIBITEURS DES FAMILLES ERK1/2 ET BCL-2
  申请人：BIOMED VALLEY DISCOVERIES INC

  公开号：WO2015095834A2

  公开（公告）日：2015-06-25

  The present invention provides, inter alia, methods for treating or ameliorating the effects of a cancer in a subject in need thereof. These methods include administering to the subject an effective amount of (i) an ERK1/2 inhibitor (such as BVD-523) or a pharmaceutically acceptable salt thereof and (ii) a BCL-2 family inhibitor (such as navitoclax) or a pharmaceutically acceptable salt thereof, to treat or ameliorate the effects of the cancer. Kits and pharmaceutical compositions for treating or ameliorating the effects of a cancer in a subject and methods for selecting a subject with cancer that may benefit from a combination drug therapy are also provided.