5-bromo-2-chloro-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]pyrimidine | 335063-14-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-bromo-2-chloro-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]pyrimidine
• CAS: 335063-14-4
• 化学式: C₁₃H₁₅BrClN₅
• 分子量: 356.653
• InChiKey: ZYMXRTSXEDZFJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2-chloro-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]pyrimidine 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 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
• 作为产物：
  描述：

  1-Cbz-4-哌啶酮 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 5-bromo-2-chloro-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]pyrimidine
  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

• Heterocyclic sodium/proton exchange inhibitors and method
  申请人：Ahmad Saleem

  公开号：US06887870B1

  公开（公告）日：2005-05-03

  Heterocyclic are provided which are sodium/proton exchange (NHE) inhibitors which have the structure wherein n is 1 to 5; X is N or C—R 5 wherein R 5 is H, halo, alkenyl, alkynyl, alkoxy, alkyl, aryl or heteroaryl; Z is a heteroaryl gorup, R 1 , R 2 , R 3 and R 4 are as defined herein, and where X is N. R 1 is preferably aryl or heteroaryl, and are useful as antianginal and cardioprotective agents. In addition, a method is provided for preventing or treating angina pectoris, cardiac dysfunction, myocardial necrosis, and arrhythmia employing the above heterocyclic derivatives.

  提供了杂环化合物，这些化合物是钠/质子交换（NHE）抑制剂，其结构如下： 其中n为1至5；X为N或C—R5，其中R5为H、卤素、烯基、炔基、烷氧基、烷基、芳基或杂芳基；Z为杂芳基团，R1、R2、R3和R4如本文所定义，且其中X为N。R1最好为芳基或杂芳基，并且可用作抗心绞痛和心脏保护剂。此外，提供了一种方法，用于预防或治疗心绞痛、心脏功能障碍、心肌坏死和心律失常，采用上述杂环衍生物。
• US7326705B2
  申请人：——

  公开号：US7326705B2

  公开（公告）日：2008-02-05
• 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.