4-chloromethyl isothiazole | 89033-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-chloromethyl isothiazole
• 英文别名: 4-(Chloromethyl)-1,2-thiazole
• CAS: 89033-79-4
• 化学式: C₄H₄ClNS
• mdl: MFCD18251007
• 分子量: 133.601
• InChiKey: PLOSCALOUKVAQO-UHFFFAOYSA-N

物化性质

• 沸点：
  116.4±22.0 °C(Predicted)
• 密度：
  1.338±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氟-4-羟基苯腈 、 4-chloromethyl isothiazole 在 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 作用下， 以 丁酮 为溶剂， 反应 18.0h， 生成 2-fluoro-4-(isothiazol-4-ylmethoxy)benzonitrile
  参考文献：
  名称：

  Selective Endothelin A Receptor Antagonists. 3. Discovery and Structure−Activity Relationships of a Series of 4-Phenoxybutanoic Acid Derivatives

  摘要：

  The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

  DOI：

  10.1021/jm9707131