1-(pyrimidin-4-yl)piperidin-4-one

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(pyrimidin-4-yl)piperidin-4-one
• 英文别名: 1-(pyrimidin-4-yl)-4-piperidone；1-pyrimidin-4-ylpiperidin-4-one
• 化学式: C₉H₁₁N₃O
• 分子量: 177.206
• InChiKey: OQPRWPLDOVDIFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(pyrimidin-4-yl)piperidin-4-one 在 四氢吡咯 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 8.5h， 生成 (S)-3-(4-(azetidine-1-carbonyl)phenoxy)-5-((1-methoxypropan-2-yl)oxy)-N-(5-(pyrimidin-4-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)benzamide
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051
• 作为产物：
  描述：

  4-哌啶酮缩乙二醇 在 盐酸 、 palladium diacetate 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 8.25h， 生成 1-(pyrimidin-4-yl)piperidin-4-one
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051

文献信息

• Antidepressant heterocyclic compounds
  申请人：Bristol-Myers Squibb Company

  公开号：US06225324B1

  公开（公告）日：2001-05-01

  Compounds of formula I are useful antidepressant agents demonstrating potent inhibition of 5-HT reuptake. Z is selected from among various phenyl and hetaryl moieties while Y is benzyl or indolyl.

  式I的化合物是有用的抗抑郁药物，表现出对5-HT再摄取的强效抑制作用。Z从各种苯基和杂环基团中选择，而Y是苄基或吲哚基。
• ANTIDEPRESSANT HETEROCYCLIC COMPOUNDS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1146871A1

  公开（公告）日：2001-10-24
• EP1146871A4
  申请人：——

  公开号：EP1146871A4

  公开（公告）日：2002-04-17
• US5972947A
  申请人：——

  公开号：US5972947A

  公开（公告）日：1999-10-26
• US6225324B1
  申请人：——

  公开号：US6225324B1

  公开（公告）日：2001-05-01