ethyl 2-amino-6-bromo-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate | 1063714-09-9

• 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: ethyl 2-amino-6-bromo-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
• CAS: 1063714-09-9
• 化学式: C₁₆H₁₈BrNO₅
• 分子量: 384.227
• InChiKey: HRUCPMAUFWZHHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-噻吩硼酸甲基亚氨基二乙酸酯 、 ethyl 2-amino-6-bromo-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate 在 四(三苯基膦)钯 作用下， 以25%的产率得到ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-(thiophen-2-yl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationship (SAR) Study of Ethyl 2-Amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017) and the Potential of the Lead against Multidrug Resistance in Cancer Treatment

  摘要：

  Multidrug resistance (MDR) against standard therapies poses a serious challenge in cancer treatment, and there is a clinical need for new anticancer agents that would selectively target MDR malignancies. Our previous studies have identified a 4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR cancer cells. To further improve its potency, we have performed detailed structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the 4H-chromene system. The results reveal that the 3 and 4 positions prefer rigid and hydrophobic functional groups while the 6 position prefers a meta or para-substituted aryl functional group and the substituent should be small and hydrophilic. We have also identified and characterized nine MDR cancer cells that acquire MDR through different mechanisms and demonstrated the scope of our new lead, 9g, to selectively target different MDR cancers, which holds promise to help manage MDR in cancer treatment.

  DOI：

  10.1021/jm300515q
• 作为产物：
  描述：

  5-溴水杨醛 在 sodium 、 三氯氧磷 作用下， 反应 4.0h， 生成 ethyl 2-amino-6-bromo-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  WO2008/118802

  摘要：

  公开号：

文献信息

• Structure−Activity Relationship and Molecular Mechanisms of Ethyl 2-Amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4<i>H</i>-chromene-3-carboxylate (sHA 14-1) and Its Analogues
  作者：Sonia G. Das、Jignesh M. Doshi、Defeng Tian、Sadiya N. Addo、Balasubramanian Srinivasan、David L. Hermanson、Chengguo Xing

  DOI：10.1021/jm9005059

  日期：2009.10.8

  excitingly, our studies of 5q in camptothecin (CCRF-CEM/C2) and mitoxantrone (HL-60/MX2) resistant cancer cells highlight its ability to selectively kill drug-resistant cells over parent cancer cells. 5q inhibits tumor cell growth through the induction of apoptosis, with detailed mechanism of its selectivity toward drug-resistant cancer cells under investigation. These results suggest that 5q is a promising

  对当前疗法的多种耐药性的快速发展是癌症治疗中的主要障碍。因此，可以克服癌细胞中获得的耐药性的抗癌剂非常重要。以前，我们已经证明2-氨基-4-（2-乙氧基-2-氧代乙基）-6-苯基-4 H-苯甲基-3-羧酸乙酯（5a，sHA 14-1）是乙基2的稳定类似物-氨基-6-溴-4-（1-氰基-2-乙氧基-2-氧代乙基）-4 H-苯甲基-3-羧酸盐（6，HA 14-1），减轻耐药性并与多种癌症协同作用白血病细胞的疗法。5a的结构活性关系（SAR）研究指导了乙基2-氨基-6-（3'，5'-二甲氧基苯基）-4-（2-乙氧基-2-氧代乙基）-4的发展H - chromene -3-carboxylate（5q，CXL017），一种对多种血液学和实体瘤细胞具有低微摩尔细胞毒性的化合物。更令人兴奋的是，我们对喜树碱（CCRF-CEM / C2）和米托蒽醌（HL-60 / MX2）耐药癌细胞中的5q的研究突显了
• [EN] THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR<br/>[FR] COMBINAISONS THÉRAPEUTIQUES D'UN INHIBITEUR DE BTK, D'UN INHIBITEUR DE PI3K, D'UN INHIBITEUR DE JAK-2, ET/OU D'UN INHIBITEUR DE BCL-2
  申请人：ACERTA PHARMA BV

  公开号：WO2016024230A1

  公开（公告）日：2016-02-18

  Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

  本发明描述了磷脂酰肌醇3-激酶（PI3K）抑制剂的治疗组合，包括选择性作用于γ-和δ-异构体以及同时选择性作用于γ-和δ-异构体（PI3K-γ,δ, PI3K-γ和PI3K-δ）的PI3K抑制剂，一种Janus激酶-2（JAK-2）抑制剂，一种Bruton酪氨酸激酶（BTK）抑制剂，和/或一种B细胞淋巴瘤-2（BCL-2）抑制剂。在一些实施例中，本发明提供了PI3K-δ抑制剂和BTK抑制剂、JAK-2和BTK抑制剂、以及BCL-2和BTK抑制剂的治疗组合。
• Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor
  申请人：Acerta Pharma B.V.

  公开号：US11166951B2

  公开（公告）日：2021-11-09

  Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

  磷脂酰肌醇 3-激酶（PI3K）抑制剂的治疗组合，包括对γ-和δ-异构体有选择性的 PI3K 抑制剂以及对γ-和δ-异构体均有选择性的 PI3K 抑制剂（PI3K-γ、PI3K-γ 和 PI3K-δ）、δ、PI3K-γ 和 PI3K-δ）的选择性抑制剂、Janus 激酶-2 (JAK-2) 抑制剂、布鲁顿酪氨酸激酶 (BTK) 抑制剂和/或 B 细胞淋巴瘤-2 (BCL-2) 抑制剂。在一些实施方案中，本发明提供了PI3K-δ抑制剂和BTK抑制剂、JAK-2和BTK抑制剂以及BCL-2和BTK抑制剂的治疗组合。
• WO2008/118802
  申请人：——

  公开号：——

  公开（公告）日：——
• THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR
  申请人：Acerta Pharma B.V.

  公开号：EP3179991A1

  公开（公告）日：2017-06-21