2-(6-Cyano-1,3-benzodioxol-5-yl)acetyl chloride | 1027592-18-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 2-(6-Cyano-1,3-benzodioxol-5-yl)acetyl chloride
• CAS: 1027592-18-2
• 化学式: C₁₀H₆ClNO₃
• 分子量: 223.616
• InChiKey: DTEGZHCQIPUATJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(6-Cyano-1,3-benzodioxol-5-yl)acetyl chloride 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 N-(4-chloro-3-methyl-5-isoxazolyl)-2-[3,4-(methylenedioxy)-6-cyano]phenylacetyl-3-thiophenesulfonamide
  参考文献：
  名称：

  Discovery of TBC11251, a Potent, Long Acting, Orally Active Endothelin Receptor-A Selective Antagonist

  摘要：

  Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ETA receptors with a K-i of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM). This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with a K-i of 0.686 nM and a pA(2) of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ETA antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ETA receptors in diseases.

  DOI：

  10.1021/jm9700068
• 作为产物：
  描述：

  methyl 2-(6-bromobenzo[d][1,3]dioxol-5-yl)acetate 在 sodium hydroxide 、 氯化亚砜 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 生成 2-(6-Cyano-1,3-benzodioxol-5-yl)acetyl chloride
  参考文献：
  名称：

  Discovery of TBC11251, a Potent, Long Acting, Orally Active Endothelin Receptor-A Selective Antagonist

  摘要：

  Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ETA receptors with a K-i of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM). This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with a K-i of 0.686 nM and a pA(2) of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ETA antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ETA receptors in diseases.

  DOI：

  10.1021/jm9700068

文献信息

• Discovery of TBC11251, a Potent, Long Acting, Orally Active Endothelin Receptor-A Selective Antagonist
  作者：Chengde Wu、Ming F. Chan、Fiona Stavros、B. Raju、Ilya Okun、Seymour Mong、Karin M. Keller、Tommy Brock、Timothy P. Kogan、Richard A. F. Dixon

  DOI：10.1021/jm9700068

  日期：1997.5.1

  Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ETA receptors with a K-i of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM). This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with a K-i of 0.686 nM and a pA(2) of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ETA antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ETA receptors in diseases.