Ani9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Ani9
• 英文别名: 2-(4-chloro-2-methylphenoxy)-N-[(2-methoxyphenyl)methylideneamino]acetamide
• 化学式: C₁₇H₁₇ClN₂O₃
• 分子量: 332.787
• InChiKey: KDALDZRKOBJXIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ani9 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 1.0h， 生成 2-(4-chloro-2-methylphenoxy)-N'-(2-methoxybenzyl)acetohydrazide
  参考文献：
  名称：

  PHARMACEUTICAL COMPOSITION FOR ANO1 ANTAGONIST WITH ANTICANCER ACTIVITY

  摘要：

  本公开涉及一种新型抗癌药物组合。本公开通过使用一种有效抑制ANO1（TMEM16A）表达的化合物实现抗癌效果。此外，本公开提供了一种使用抑制ANO1（TMEM16A）表达的化合物的ANO1（TMEM16A）拮抗剂。

  公开号：

  US20200087250A1
• 作为产物：
  描述：

  邻甲氧基苯甲醛 、 2-(4-氯-2-甲基苯氧基)乙酸肼 以 乙醇 为溶剂， 反应 1.0h， 以90%的产率得到Ani9
  参考文献：
  名称：

  Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)

  摘要：

  Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50 of similar to 30 nM, similar to 3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.

  DOI：

  10.1021/acs.jmedchem.7b00020

文献信息

• Pharmaceutical composition for ANO1 antagonist with anticancer activity
  申请人：INDUSTRY-ACADEMIC COOPERATION FOUNDATION, YONSEI UNIVERSITY

  公开号：US11274074B2

  公开（公告）日：2022-03-15

  The present disclosure relates to a novel anticancer pharmaceutical composition. The present disclosure achieves an anticancer effect using a compound effective in inhibiting the expression of ANO1 (TMEM16A). In addition, the present disclosure provides an ANO1 (TMEM16A) antagonist using the compound inhibiting the expression of ANO1 (TMEM16A).

  本公开涉及一种新型抗癌药物组合物。本公开利用有效抑制 ANO1 (TMEM16A) 表达的化合物达到抗癌效果。此外，本公开还提供了一种使用抑制 ANO1 (TMEM16A) 表达的化合物的 ANO1 (TMEM16A) 拮抗剂。
• Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)
  作者：Eric C. Truong、Puay W. Phuan、Amanda L. Reggi、Loretta Ferrera、Luis J. V. Galietta、Sarah E. Levy、Alannah C. Moises、Onur Cil、Elena Diez-Cecilia、Sujin Lee、Alan S. Verkman、Marc O. Anderson

  DOI：10.1021/acs.jmedchem.7b00020

  日期：2017.6.8

  Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50 of similar to 30 nM, similar to 3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.
• PHARMACEUTICAL COMPOSITION FOR ANO1 ANTAGONIST WITH ANTICANCER ACTIVITY
  申请人：INDUSTRY-ACADEMIC COOPERATION FOUNDATION, YONSEI UNIVERSITY

  公开号：US20200087250A1

  公开（公告）日：2020-03-19

  The present disclosure relates to a novel anticancer pharmaceutical composition. The present disclosure achieves an anticancer effect using a compound effective in inhibiting the expression of ANO1 (TMEM16A). In addition, the present disclosure provides an ANO1 (TMEM16A) antagonist using the compound inhibiting the expression of ANO1 (TMEM16A).

  本公开涉及一种新型抗癌药物组合。本公开通过使用一种有效抑制ANO1（TMEM16A）表达的化合物实现抗癌效果。此外，本公开提供了一种使用抑制ANO1（TMEM16A）表达的化合物的ANO1（TMEM16A）拮抗剂。