3-(5-tert-butyl-isoxazol-3-yl)-2-[(4-chlorophenyl)-hydrazono]-3-oxo-propionitrile | 263707-17-1

• 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: 3-(5-tert-butyl-isoxazol-3-yl)-2-[(4-chlorophenyl)-hydrazono]-3-oxo-propionitrile
• 英文别名: 2-(5-tert-butyl-1,2-oxazol-3-yl)-N-(4-chloroanilino)-2-oxoethanimidoyl cyanide
• CAS: 263707-17-1
• 化学式: C₁₆H₁₅ClN₄O₂
• 分子量: 330.774
• InChiKey: FVOOXEZIGUERJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-hydroxy-5,5-dimethyl-4-oxohex-2-enoate 在 盐酸 、 四丁基氟化铵 、 甲基锂 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 反应 5.58h， 生成 3-(5-tert-butyl-isoxazol-3-yl)-2-[(4-chlorophenyl)-hydrazono]-3-oxo-propionitrile
  参考文献：
  名称：

  高效合成 ESI-09，一种新型非环核苷酸 EPAC 拮抗剂

  摘要：

  报道了一种简洁有效的合成方法来生产新型非环核苷酸 EPAC 拮抗剂ESI-09及其新类似物。该合成的主要特点包括温和可靠的异恶唑合成子一锅法，以及氰甲基酮关键中间体的改良一锅法。该合成需要廉价的起始材料和仅三个线性步骤即可完成，总产率为 53%。

  DOI：

  10.1016/j.tetlet.2013.01.024

文献信息

• Structure–Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-<i>N</i>′-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists
  作者：Na Ye、Yingmin Zhu、Haijun Chen、Zhiqing Liu、Fang C. Mei、Christopher Wild、Haiying Chen、Xiaodong Cheng、Jia Zhou

  DOI：10.1021/acs.jmedchem.5b00635

  日期：2015.8.13

  Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of the pivotal second messenger cAMP, thereby regulating a wide variety of intracellular physiological and pathophysiological processes. A series of novel 2-(isoxazol-3yl)-2-oxo-N'-phenyl-acetohydrazonoyl cyanide EPAC antagonists was synthesized and evaluated in an effort to optimize properties of the previously identified high-throughput (HTS) hit 1 (ESI-09). Structure activity relationship (SAR) analysis led to the discovery of several more active EPAC antagonists (e.g., 22 (HJC0726), 35 (NY0123), and 47 (NY0173)) with low micromolar inhibitory activity. These inhibitors may serve as valuable pharmacological probes to facilitate our efforts in elucidating the biological functions of EPAC and developing potential novel therapeutics against human diseases. Our SAR ring as well as the 5-position of the results have also revealed that further modification at the 3-, 4-, and 5-positions of the phenyl isoxazole moiety may allow for the development of more potent EPAC antagonists.
• Efficient synthesis of ESI-09, a novel non-cyclic nucleotide EPAC antagonist
  作者：Haijun Chen、Chunyong Ding、Christopher Wild、Huiling Liu、Tianzhi Wang、Mark A. White、Xiaodong Cheng、Jia Zhou

  DOI：10.1016/j.tetlet.2013.01.024

  日期：2013.3

  A concise and efficient synthetic approach to producing a novel non-cyclic nucleotide EPAC antagonist ESI-09 and its new analogs is reported. Key features of the synthesis include a mild and reliable one-pot procedure for an isoxazole synthon, as well as a modified one-pot protocol for the cyanomethyl ketone key intermediate. The synthesis requires inexpensive starting materials and only three linear

  报道了一种简洁有效的合成方法来生产新型非环核苷酸 EPAC 拮抗剂ESI-09及其新类似物。该合成的主要特点包括温和可靠的异恶唑合成子一锅法，以及氰甲基酮关键中间体的改良一锅法。该合成需要廉价的起始材料和仅三个线性步骤即可完成，总产率为 53%。