N-(5-(tert-butyl)isoxazol-3-yl)-3-chlorobenzamide | 959239-93-1

• 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: N-(5-(tert-butyl)isoxazol-3-yl)-3-chlorobenzamide
• 英文别名: N-(5-tert-butyl-1,2-oxazol-3-yl)-3-chlorobenzamide
• CAS: 959239-93-1
• 化学式: C₁₄H₁₅ClN₂O₂
• mdl: MFCD09873353
• 分子量: 278.738
• InChiKey: SPZCTBVXUJWIIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基-5-叔丁基异唑 、 3-氯苯甲酸 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以33%的产率得到N-(5-(tert-butyl)isoxazol-3-yl)-3-chlorobenzamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-N′-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00635

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.