2-(5-(4-fluoro-3-methylphenyl)-4-(4-(4-methyl-1H-imidazol-5-yl)piperidin-1-yl)pyrimidin-2-yl)acetonitrile | 911497-67-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(5-(4-fluoro-3-methylphenyl)-4-(4-(4-methyl-1H-imidazol-5-yl)piperidin-1-yl)pyrimidin-2-yl)acetonitrile
• 英文别名: 2-[5-(4-fluoro-3-methylphenyl)-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]pyrimidin-2-yl]acetonitrile
• CAS: 911497-67-1
• 化学式: C₂₂H₂₃FN₆
• 分子量: 390.463
• InChiKey: JALZOHCTXJCEQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(5-(4-fluoro-3-methylphenyl)-4-(4-(4-methyl-1H-imidazol-5-yl)piperidin-1-yl)pyrimidin-2-yl)acetonitrile 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors

  摘要：

  A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 mu M) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.077
• 作为产物：
  描述：

  1-Cbz-4-哌啶酮 在 四(三苯基膦)钯 、 potassium tert-butylate 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 2-(5-(4-fluoro-3-methylphenyl)-4-(4-(4-methyl-1H-imidazol-5-yl)piperidin-1-yl)pyrimidin-2-yl)acetonitrile
  参考文献：
  名称：

  Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors

  摘要：

  A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 mu M) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.077

文献信息

• Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors
  作者：Karnail S. Atwal、Steven V. O’Neil、Saleem Ahmad、Lidia Doweyko、Mark Kirby、Charles R. Dorso、Gamini Chandrasena、Bang-Chi Chen、Rulin Zhao、Robert Zahler

  DOI：10.1016/j.bmcl.2006.06.077

  日期：2006.9

  A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 mu M) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies. (c) 2006 Elsevier Ltd. All rights reserved.