4-(1-Methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxylic acid | 1401992-33-3

• 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: 4-(1-Methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxylic acid
• 英文别名: 4-(1-methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxylic acid
• CAS: 1401992-33-3
• 化学式: C₁₃H₁₇N₃O₃
• 分子量: 263.296
• InChiKey: OCNSTQHLSQXWIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-aminotricyclo[3.3. 1.1^3,7]decan-1-ol 、 4-(1-Methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-[(2r,5s)-5-hydroxyadamantan-2-yl]-4-(1-methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxamide
  参考文献：
  名称：

  Optimisation of pharmacokinetic properties in a neutral series of 11β-HSD1 inhibitors

  摘要：

  11 beta-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11 beta-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.070
• 作为产物：
  描述：

  ethyl 3-(1-methylcyclopropyl)-3-oxopropanoate 在 sodium methylate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 15.0h， 生成 4-(1-Methylcyclopropyl)-2-morpholin-4-ylpyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Optimisation of pharmacokinetic properties in a neutral series of 11β-HSD1 inhibitors

  摘要：

  11 beta-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11 beta-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.070

文献信息

• Optimisation of pharmacokinetic properties in a neutral series of 11β-HSD1 inhibitors
  作者：James S. Scott、Adrian L. Gill、Linda Godfrey、Sam D. Groombridge、Amanda Rees、John Revill、Paul Schofield、Pernilla Sörme、Andrew Stocker、John G. Swales、Paul R.O. Whittamore

  DOI：10.1016/j.bmcl.2012.08.070

  日期：2012.11

  11 beta-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11 beta-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution. (C) 2012 Elsevier Ltd. All rights reserved.