1-[2-(benzimidazol-2-ylthio)ethyl]piperazine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine hydrochloride
• 化学式: C₁₃H₁₈N₄S*ClH
• 分子量: 298.84
• InChiKey: XKNYSYBICJDEAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  43.95
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(6-methyl-2,4-bis(methylthio)pyridin-3-yl)acetamide 、 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine hydrochloride 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methyl-3-pyridyl]acetamide
  参考文献：
  名称：

  EP1767527

  摘要：

  公开号：
• 作为产物：
  描述：

  4-[2-(1H-苯并咪唑-2-基硫基)乙基]-1-哌嗪甲醛 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以97%的产率得到1-[2-(benzimidazol-2-ylthio)ethyl]piperazine hydrochloride
  参考文献：
  名称：

  Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor

  摘要：

  We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 degrees C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 mu L/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.

  DOI：

  10.1016/j.bmc.2020.115457

文献信息

• PROCESSES FOR PRODUCTION OF CYCLIC DIAMINE COMPOUNDS OR SALTS THEREOF
  申请人：Kowa Co., Ltd.

  公开号：EP1460065B1

  公开（公告）日：2012-12-05
• PROCESS FOR PRODUCTION OF 1- 2-(BENZIMIDAZOL-2-YL- THIO)ETHYL PIPERAZINE OR SALTS THEREOF
  申请人：Kowa Co., Ltd.

  公开号：EP1566381B1

  公开（公告）日：2009-11-11
• EP1767527
  申请人：——

  公开号：——

  公开（公告）日：——
• Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor
  作者：Kimiyuki Shibuya、Toru Miura、Tadaaki Ohgiya、Kozo Omichi、Yoshihiko Tsunenari

  DOI：10.1016/j.bmc.2020.115457

  日期：2020.6

  We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 degrees C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 mu L/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.