3-bromo-2-(dibromomethyl)pyridine | 865449-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-bromo-2-(dibromomethyl)pyridine
• 英文别名: Pyridine, 3-bromo-2-(dibromomethyl)-
• CAS: 865449-17-8
• 化学式: C₆H₄Br₃N
• 分子量: 329.816
• InChiKey: CLMUDUURKHDMRP-UHFFFAOYSA-N

物化性质

• 沸点：
  292.7±35.0 °C(Predicted)
• 密度：
  2.318±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromo-2-(dibromomethyl)pyridine 在 吗啉 、 copper(l) iodide 、 双三苯基磷二氯化钯 、 氨 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 1,7-萘啶
  参考文献：
  名称：

  Optimization of Potency and Pharmacokinetic Properties of Tetrahydroisoquinoline Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values < 3 mg/kg.

  DOI：

  10.1021/jm401955h
• 作为产物：
  描述：

  2-甲基-3-溴吡啶 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 30.0h， 以83.5%的产率得到3-bromo-2-(dibromomethyl)pyridine
  参考文献：
  名称：

  [EN] TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
  [FR] ANTAGONISTES DE TRPM8 ET LEUR UTILISATION DANS LE CADRE THÉRAPEUTIQUE

  摘要：

  式（I）的化合物可用作TRPM8的拮抗剂。这些化合物在治疗许多TRPM8介导的疾病和症状方面具有用处，并可用于制备用于治疗这些疾病和症状的药物和药物组合物。这些疾病的例子包括但不限于偏头痛和神经病性疼痛。式（I）的化合物具有上述结构，其中变量的定义在此提供。

  公开号：

  WO2012177896A1

文献信息

• [EN] TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS<br/>[FR] ANTAGONISTES DE TRPM8 ET LEUR UTILISATION DANS LE CADRE THÉRAPEUTIQUE
  申请人：AMGEN INC

  公开号：WO2012177896A1

  公开（公告）日：2012-12-27

  Compounds of Formula (I) are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula (I) have the above structure, where the definitions of the variables are provided herein.

  式（I）的化合物可用作TRPM8的拮抗剂。这些化合物在治疗许多TRPM8介导的疾病和症状方面具有用处，并可用于制备用于治疗这些疾病和症状的药物和药物组合物。这些疾病的例子包括但不限于偏头痛和神经病性疼痛。式（I）的化合物具有上述结构，其中变量的定义在此提供。
• TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
  申请人：BROWN James

  公开号：US20130158034A1

  公开（公告）日：2013-06-20

  Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  式I的化合物是TRPM8拮抗剂，对于治疗许多TRPM8介导的疾病和症状有用，并可用于制备治疗此类疾病和症状的药物和制剂。此类疾病的例子包括但不限于偏头痛和神经病性疼痛。式I的化合物具有以下结构：其中变量的定义在此提供。
• TRPM8 antagonists and their use in treatments
  申请人：Brown James

  公开号：US08778941B2

  公开（公告）日：2014-07-15

  Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物可用作TRPM8的拮抗剂。这些化合物可用于治疗多种TRPM8介导的疾病和病症，并可用于制备用于治疗此类疾病和病症的药物和制剂。此类疾病的示例包括但不限于偏头痛和神经病性疼痛。公式I的化合物具有以下结构：其中变量的定义在此提供。
• Synthesis and σ receptor affinity of regioisomeric spirocyclic furopyridines
  作者：Kengo Miyata、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1016/j.ejmech.2014.06.073

  日期：2014.8

  In order to investigate systematically the effect of the position of the pyridine N-atom on the σ1 receptor affinity four regioisomeric furopyridines 2a-d were synthesized and pharmacologically evaluated. The key steps of the synthesis comprise bromine/lithium exchange at regioisomeric bromopyridinecarbaldehyde acetals 7a-d, subsequent addition to 1-benzylpiperidin-4-one and cyclization. The regioisomeric acetals 7a-d were obtained either by o-metalation of bromopyridines 5b and 5c or by oxidation of bromopicolines 3a and 3d. In radioligand binding studies the regioisomeric furopyridines 2a-d showed 7- to 12-fold lower σ1 affinity than the benzofuran analog 1. The reduced σ1 affinity of the furopyridines 2a-d is explained with the reduced electron density of the pyridine ring. Since the four regioisomeric furopyridines show almost the same σ1 affinity (Ki = 4.9-10 nM), a directed interaction of the pyridine N-atom with the receptor protein can be excluded.
• [EN] TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS<br/>[FR] ANTAGONISTES DE TRPM8 ET LEUR UTILISATION DANS DES TRAITEMENTS
  申请人：AMGEN INC

  公开号：WO2012177893A3

  公开（公告）日：2013-06-13