4-butyl-2-methylpyrimidine-5-carboxylic acid | 1191097-09-2

• 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-butyl-2-methylpyrimidine-5-carboxylic acid
• CAS: 1191097-09-2
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: QSIXJTDOIKZRMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-aminotricyclo[3.3. 1.1^3,7]decan-1-ol 、 4-butyl-2-methylpyrimidine-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
  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：

  3-氧代庚酸乙酯 在 sodium methylate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 13.0h， 生成 4-butyl-2-methylpyrimidine-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

• SUBSTITUTED PYRIMIDIN-5-CARBOXAMIDES 281
  申请人：GILL Adrian Liam

  公开号：US20090264401A1

  公开（公告）日：2009-10-22

  A compound of formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  一种具有化学式（I）的化合物： 及其药用盐，其中变量基团在其中定义；还描述了它们在抑制11βHSD1中的应用，制备它们的方法以及包含它们的药物组合物。
• [EN] SUBSTITUTED PYRIMIDIN-5-CARBOXAMIDES 281<br/>[FR] PYRIMIDINE-5-CARBOXAMIDES SUBSTITUÉS
  申请人：ASTRAZENECA AB

  公开号：WO2009130496A1

  公开（公告）日：2009-10-29

  A compound of formula (I) and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.
• 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.