N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)formamidine | 570386-28-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)formamidine
• 英文别名: N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)-formamidine；N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)methanimidamide
• CAS: 570386-28-6
• 化学式: C₉H₁₁N₅
• 分子量: 189.22
• InChiKey: PVKUFVZYVRHBCW-UHFFFAOYSA-N

物化性质

• 沸点：
  389.7±34.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)formamidine 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 反应 48.0h， 生成 7-(1-methylpiperidin-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-2-ylamine
  参考文献：
  名称：

  Novel Potent 5-HT_1F Receptor Agonists:  Structure−Activity Studies of a Series of Substituted N-[3-(1-Methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]amides

  摘要：

  Compound 1a (LY334370), a selective 5-HT1F receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clinical efficacy for the acute treatment of migraine. Although 1 was greater than 100-fold selective over both the 5-HT1B and 5-HT1D receptors, it exhibited appreciable 5-HT1A receptor affinity. Described here is the synthesis and evaluation of a series of pyrrolo[2,3-c]pyridine and pyrrolo[3,2-b]pyridine (2a and 3a) as well as pyrrolo[3,2-d]pyrimidine (4a) analogues of 1, compounds prepared in an effort to identify SSOFRAs with improved selectivity over other 5-HT1 receptor subtypes. The pyrrolo [3,2-b] pyridine analogue 3a showed high 5-HT1F receptor affinity but offered no improvement in selectivity compared to 1. However, the C-5 acetamide derivative, 3b, was greater than 100-fold selective over the 5-HT1A, 5-HT1B, and 5-HT1D receptors. SAR studies of this series determined that alkylamides in particular exhibited high selectivity for the 5-HT1F receptor. Replacement at C-5 with other substituents decreased affinity or selectivity. These SAR studies identified SSOFRAs that demonstrated oral activity in the neurogenic plasma protein extravasation model, a model indicative of antimigraine activity.

  DOI：

  10.1021/jm030020m
• 作为产物：
  描述：

  2-氨基-6-甲基-5-硝基-3H-嘧啶-4-酮 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~115.0 ℃ 、413.68 kPa 条件下， 反应 4.5h， 生成 N,N-dimethyl-N'-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)formamidine
  参考文献：
  名称：

  Novel Potent 5-HT_1F Receptor Agonists:  Structure−Activity Studies of a Series of Substituted N-[3-(1-Methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]amides

  摘要：

  Compound 1a (LY334370), a selective 5-HT1F receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clinical efficacy for the acute treatment of migraine. Although 1 was greater than 100-fold selective over both the 5-HT1B and 5-HT1D receptors, it exhibited appreciable 5-HT1A receptor affinity. Described here is the synthesis and evaluation of a series of pyrrolo[2,3-c]pyridine and pyrrolo[3,2-b]pyridine (2a and 3a) as well as pyrrolo[3,2-d]pyrimidine (4a) analogues of 1, compounds prepared in an effort to identify SSOFRAs with improved selectivity over other 5-HT1 receptor subtypes. The pyrrolo [3,2-b] pyridine analogue 3a showed high 5-HT1F receptor affinity but offered no improvement in selectivity compared to 1. However, the C-5 acetamide derivative, 3b, was greater than 100-fold selective over the 5-HT1A, 5-HT1B, and 5-HT1D receptors. SAR studies of this series determined that alkylamides in particular exhibited high selectivity for the 5-HT1F receptor. Replacement at C-5 with other substituents decreased affinity or selectivity. These SAR studies identified SSOFRAs that demonstrated oral activity in the neurogenic plasma protein extravasation model, a model indicative of antimigraine activity.

  DOI：

  10.1021/jm030020m

文献信息

• Indazole compounds
  申请人：Ericsson M. Anna

  公开号：US20070282101A1

  公开（公告）日：2007-12-06

  Novel compounds of Formula (I) or pharmaceutically acceptable salts, prodrugs and biologically active metabolites thereof of Formula (I) wherein the substituents are as defined herein, which are useful as therapeutic agents.

  本发明提供了化合物(I)或其药学上可接受的盐、前药和生物活性代谢物，其中取代基如定义所述，这些化合物可用作治疗剂。
• Indazole Compounds
  申请人：Ericson Anna M.

  公开号：US20120053345A1

  公开（公告）日：2012-03-01

  Novel compounds of Formula (I) or pharmaceutically acceptable salts, prodrugs and biologically active metabolites thereof of Formula (I) wherein the substituents are as defined herein, which are useful as therapeutic agents.

  本发明涉及化合物(I)或其药学上可接受的盐、前药和生物活性代谢物，其中取代基的定义如本文所述，这些化合物可用作治疗剂。
• Novel Potent 5-HT_1F Receptor Agonists:  Structure−Activity Studies of a Series of Substituted <i>N</i>-[3-(1-Methyl-4-piperidinyl)-1<i>H</i>-pyrrolo[3,2-<i>b</i>]pyridin-5-yl]amides
  作者：Sandra A. Filla、Brian M. Mathes、Kirk W. Johnson、Lee A. Phebus、Marlene L. Cohen、David L. Nelson、John M. Zgombick、Jon A. Erickson、Kathryn W. Schenck、David B. Wainscott、Theresa A. Branchek、John M. Schaus

  DOI：10.1021/jm030020m

  日期：2003.7.1

  Compound 1a (LY334370), a selective 5-HT1F receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clinical efficacy for the acute treatment of migraine. Although 1 was greater than 100-fold selective over both the 5-HT1B and 5-HT1D receptors, it exhibited appreciable 5-HT1A receptor affinity. Described here is the synthesis and evaluation of a series of pyrrolo[2,3-c]pyridine and pyrrolo[3,2-b]pyridine (2a and 3a) as well as pyrrolo[3,2-d]pyrimidine (4a) analogues of 1, compounds prepared in an effort to identify SSOFRAs with improved selectivity over other 5-HT1 receptor subtypes. The pyrrolo [3,2-b] pyridine analogue 3a showed high 5-HT1F receptor affinity but offered no improvement in selectivity compared to 1. However, the C-5 acetamide derivative, 3b, was greater than 100-fold selective over the 5-HT1A, 5-HT1B, and 5-HT1D receptors. SAR studies of this series determined that alkylamides in particular exhibited high selectivity for the 5-HT1F receptor. Replacement at C-5 with other substituents decreased affinity or selectivity. These SAR studies identified SSOFRAs that demonstrated oral activity in the neurogenic plasma protein extravasation model, a model indicative of antimigraine activity.