I+/-,I+/-,5-Trimethyl-6-(4-morpholinyl)-3-pyridinemethanamine | 566158-49-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: I+/-,I+/-,5-Trimethyl-6-(4-morpholinyl)-3-pyridinemethanamine
• 英文别名: 2-(5-methyl-6-morpholin-4-ylpyridin-3-yl)propan-2-amine
• CAS: 566158-49-4
• 化学式: C₁₃H₂₁N₃O
• 分子量: 235.329
• InChiKey: OWULFUBBYXTIMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  51.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-fluoro-9-oxo-9,10-dihydro-acridine-3-carboxylic acid 、 I+/-,I+/-,5-Trimethyl-6-(4-morpholinyl)-3-pyridinemethanamine 在 N,N-bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以3.31 g的产率得到2-fluoro-N-{2-[5-methyl-6-(morpholin-4-yl)pyridin-3-yl]propan-2-yl}-9-oxo-9,10-dihydroacridine-3-carboxamide
  参考文献：
  名称：

  Acridone-Based Inhibitors of Inosine 5‘-Monophosphate Dehydrogenase:  Discovery and SAR Leading to the Identification of N-(2-(6-(4-Ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)

  摘要：

  Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  DOI：

  10.1021/jm070299x
• 作为产物：
  描述：

  5-Methyl-6-morpholin-4-yl-nicotinonitrile 、 甲基锂 在 cerium(III) chloride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.5h， 以3.10 g的产率得到I+/-,I+/-,5-Trimethyl-6-(4-morpholinyl)-3-pyridinemethanamine
  参考文献：
  名称：

  Acridone-Based Inhibitors of Inosine 5‘-Monophosphate Dehydrogenase:  Discovery and SAR Leading to the Identification of N-(2-(6-(4-Ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)

  摘要：

  Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  DOI：

  10.1021/jm070299x

文献信息

• US7312209B2
  申请人：——

  公开号：US7312209B2

  公开（公告）日：2007-12-25