5-(N-[3-thiophenecarbonyl]amino)-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 5-(N-[3-thiophenecarbonyl]amino)-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine
• 英文别名: N-[3-(1-methylpiperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]thiophene-3-carboxamide
• 化学式: C₁₈H₂₀N₄OS
• 分子量: 340.449
• InChiKey: MFHQYQOIPCWNJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-5-硝基-6-甲基吡啶 在 palladium on activated charcoal 吡啶 、 氢氧化钾 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~110.0 ℃ 、275.79 kPa 条件下， 反应 76.0h， 生成 5-(N-[3-thiophenecarbonyl]amino)-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine
  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

• 5-HT.sub.1F agonists
  申请人：Eli Lilly and Company

  公开号：US05817671A1

  公开（公告）日：1998-10-06

  This invention provides 5-HT.sub.1F agonists of Formula I: ##STR1## where A--B, X, and R are as defined in the specification. The invention also encompasses pharmaceutical formulations employing compounds of Formula I as well as methods of treating conditions associated with 5-HT.sub.1F activation employing these compounds or compositions. The invention also provides intermediates useful for the preparation of the compounds of Formula I.

  这项发明提供了式I的5-HT.sub.1F激动剂：##STR1##其中A-B、X和R如规范中所定义。该发明还涵盖了使用式I化合物的药物配方，以及利用这些化合物或组合物治疗与5-HT.sub.1F激活相关的疾病的方法。该发明还提供了用于制备式I化合物的中间体。
• 5-HT.sub.1F agonists intermediates
  申请人：Eli Lilly and Company

  公开号：US05998622A1

  公开（公告）日：1999-12-07

  This invention provides 5-HT.sub.1F agonists of Formula I; ##STR1## where A-B, X, and R are as defined in the specification. The invention also encompasses pharmaceutical formulations employing compounds of Formula I as well as methods of treating conditions associated with 5-HT.sub.1F activation employing these compounds or compositions. The invention also provides intermediates useful for the preparation of the compounds of Formula I.

  该发明提供了公式I的5-HT.sub.1F激动剂; ##STR1## 其中A-B，X和R如规范中所定义。该发明还包括使用公式I化合物的制药配方，以及使用这些化合物或组合物治疗与5-HT.sub.1F激活相关的疾病的方法。该发明还提供了制备公式I化合物有用的中间体。
• Nitropyridine compound
  申请人：Eli Lilly and Company

  公开号：US05919936A1

  公开（公告）日：1999-07-06

  This invention provides 5-HT.sub.1F agonists of Formula I: ##STR1## where A-B, X, and R are as defined in the specification. The invention also encompasses pharmaceutical formulations employing compounds of Formula I as well as methods of treating conditions associated with 5-HT.sub.1F activation employing these compounds or compositions. The invention also provides intermediates useful for the preparation of the compounds of Formula I.

  本发明提供了公式I的5-HT.sub.1F激动剂：##STR1## 其中A-B，X和R在规范中定义。本发明还包括使用公式I化合物的制药配方，以及使用这些化合物或组合物治疗与5-HT.sub.1F激活相关的疾病的方法。本发明还提供用于制备公式I化合物的中间体。
• 5-HT1F agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0842934A1

  公开（公告）日：1998-05-20

  This invention provides 5-HT1F agonists of Formula I: where A-B, X, and R are as defined in the specification. The invention also encompasses pharmaceutical formulations employing compounds of Formula I as well as methods of treating conditions associated with 5-HT1F activation employing these compounds or compositions.

  本发明提供了式 I 的 5-HT1F 激动剂： 其中A-B、X和R如说明书中所定义。本发明还包括采用式 I 化合物的药物制剂，以及采用这些化合物或组合物治疗与 5-HT1F 活化相关的病症的方法。
• 5-HT1F agonists in chronic pain
  申请人：ELI LILLY AND COMPANY

  公开号：EP1082958A2

  公开（公告）日：2001-03-14

  The use of a 5-HT1F agonist for the manufacture of a medicament for the treatment of chronic pain.

  使用 5-HT1F 激动剂制造治疗慢性疼痛的药物。