N-(3-chloro-5-(trifluoromethyl)phenyl)-2-(5-(furan-2-yl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide

• 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: N-(3-chloro-5-(trifluoromethyl)phenyl)-2-(5-(furan-2-yl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide
• 英文别名: N-[3-chloro-5-(trifluoromethyl)anilino]-2-[5-(furan-2-yl)-1,2-oxazol-3-yl]-2-oxoethanimidoyl cyanide
• 化学式: C₁₇H₈ClF₃N₄O₃
• 分子量: 408.724
• InChiKey: ASXMOJVUQQDEAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  5-(2-呋喃基)异恶唑-3-羧酸乙酯 在 盐酸 、 甲基锂 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 反应 1.58h， 生成 N-(3-chloro-5-(trifluoromethyl)phenyl)-2-(5-(furan-2-yl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide
  参考文献：
  名称：

  Identification of novel 2-(benzo[ d ]isoxazol-3-yl)-2-oxo- N -phenylacetohydrazonoyl cyanide analoguesas potent EPAC antagonists

  摘要：

  Two series of novel EPAC antagonists are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit 1 (ESI09). Further SAR studies reveal that the isoxazole ring A of 1 can tolerate chemical modifications with either introduction of flexible electron-donating substitutions or structurally restrictedly fusing with a phenyl ring, leading to identification of several more potent and diversified EPAC antagonists (e.g., 10 (NY0617), 14 (NY0460), 26 (NY0725), 32 (NY0561), and 33 (NY0562)) with low micromolar inhibitory activities. Molecular docking studies on compounds 10 and 33 indicate that these two series of compounds bind at a similar site with substantially different interactions with the EPAC proteins. The findings may serve as good starting points for the development of more potent EPAC antagonists as valuable pharmacological probes or potential drug candidates. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.001

文献信息

• [EN] EPAC ANTAGONISTS<br/>[FR] ANTAGONISTES D'EPAC
  申请人：ZHOU JIA

  公开号：WO2018183626A1

  公开（公告）日：2018-10-04

  Embodiments are directed to a series of novel EPAC antagonists that are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit ESI-09.

  该实施例涉及一系列新颖的EPAC拮抗剂，这些拮抗剂经过设计、合成和评估，旨在基于先前确定的高通量筛选（HTS）命中ESI-09的支架开发多样化的类似物。
• EPAC antagonists
  申请人：Zhou Jia

  公开号：US11124489B2

  公开（公告）日：2021-09-21

  Embodiments are directed to a series of novel EPAC antagonists that are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit ESI-09.

  本发明实施例涉及一系列新型 EPAC 拮抗剂，这些拮抗剂的设计、合成和评估是为了在先前确定的高通量（HTS）研究热点 ESI-09 的支架基础上开发多样化的类似物。
• EPAC ANTAGONISTS
  申请人：ZHOU Jia

  公开号：US20200255388A1

  公开（公告）日：2020-08-13

  Embodiments are directed to a series of novel EPAC antagonists that are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit ESI-09.
• Identification of novel 2-(benzo[ d ]isoxazol-3-yl)-2-oxo- N -phenylacetohydrazonoyl cyanide analoguesas potent EPAC antagonists
  作者：Na Ye、Yingmin Zhu、Zhiqing Liu、Fang C. Mei、Haiying Chen、Pingyuan Wang、Xiaodong Cheng、Jia Zhou

  DOI：10.1016/j.ejmech.2017.04.001

  日期：2017.7

  Two series of novel EPAC antagonists are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit 1 (ESI09). Further SAR studies reveal that the isoxazole ring A of 1 can tolerate chemical modifications with either introduction of flexible electron-donating substitutions or structurally restrictedly fusing with a phenyl ring, leading to identification of several more potent and diversified EPAC antagonists (e.g., 10 (NY0617), 14 (NY0460), 26 (NY0725), 32 (NY0561), and 33 (NY0562)) with low micromolar inhibitory activities. Molecular docking studies on compounds 10 and 33 indicate that these two series of compounds bind at a similar site with substantially different interactions with the EPAC proteins. The findings may serve as good starting points for the development of more potent EPAC antagonists as valuable pharmacological probes or potential drug candidates. (C) 2017 Elsevier Masson SAS. All rights reserved.