(5-bromo-6-methyl-pyridin-2-yl)-dimethyl-amine | 910054-73-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (5-bromo-6-methyl-pyridin-2-yl)-dimethyl-amine
• 英文别名: 5-Bromo-N,N,6-trimethylpyridin-2-amine
• CAS: 910054-73-8
• 化学式: C₈H₁₁BrN₂
• 分子量: 215.093
• InChiKey: MAMDEZVDBHDFOR-UHFFFAOYSA-N

物化性质

• 沸点：
  270.2±35.0 °C(Predicted)
• 密度：
  1.404±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  (5-bromo-6-methyl-pyridin-2-yl)-dimethyl-amine 在 氢溴酸肼 、 potassium tert-butylate 、 sodium hydride 、 magnesium 、 1,2-二溴乙烷 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成 [3-(6-Dimethylamino-2-methyl-pyridin-3-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-dipropyl-amine
  参考文献：
  名称：

  Design of 2,5-Dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and Structure−Activity Relationships of a Series of Potent and Orally Active Corticotropin-Releasing Factor Receptor Antagonists

  摘要：

  We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF1, receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26h exhibited good binding affinity at the human CRF1 receptor with a K-i value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF1 receptor [IC50 = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells [IC50 = 20 nM). 26h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26h was orally bioavailable and able to penetrate into the brain. 26h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF1, receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26h was developed into a clinical compound and exhibited efficacy in patients with major depression.

  DOI：

  10.1021/jm040058e
• 作为产物：
  描述：

  2-氨基-5-溴-6-甲基吡啶 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 96.5h， 以96%的产率得到(5-bromo-6-methyl-pyridin-2-yl)-dimethyl-amine
  参考文献：
  名称：

  Substituted aryl 1,4-pyrazine derivatives

  摘要：

  该发明涉及本文描述的Formula I化合物，以及其药学上可接受的盐，这些化合物作为CRF 1 拮抗剂，在治疗与CRF 1 受体相关的疾病和疾病中起作用，包括与中枢神经系统相关的疾病和疾病。

  公开号：

  US20060211710A1

文献信息

• SUBSTITUTED ARYL 1.4-PYRAZlNE DERIVATIVES
  申请人：Pfizer Products Inc.

  公开号：EP1871763A1

  公开（公告）日：2008-01-02
• [EN] SUBSTITUTED ARYL 1.4-PYRAZlNE DERIVATIVES BACKGROUND OF THE INVENTION<br/>[FR] DERIVES D'ARYL-1,4-PYRAZINE
  申请人：PFIZER PROD INC

  公开号：WO2006114666A1

  公开（公告）日：2006-11-02

  [EN] The invention is directed to compounds of Formula (I), described herein, as well as pharmaceutically acceptable salts thereof, which act as CRF₁ antagonists and are useful in the treatment of disorders and diseases associated with CRF₁ receptors, including CNS- related disorders and diseases.
  [FR] L'invention concerne les composés décrits, représentés par la formule (I), ainsi que les sels pharmaceutiquement acceptables de ces composés, qui agissent comme antagonistes du facteur CRF₁, et peuvent être utilisés pour le traitement des troubles et des maladies associés aux récepteurs de CRF₁, notamment les troubles et les maladies du SNC.
• Substituted aryl 1,4-pyrazine derivatives
  申请人：Verhoest R. Patrick

  公开号：US20060211710A1

  公开（公告）日：2006-09-21

  The invention is directed to compounds of Formula I, described herein, as well as pharmaceutically acceptable salts thereof, which act as CRF 1 antagonists and are useful in the treatment of disorders and diseases associated with CRF 1 receptors, including CNS-related disorders and diseases.

  该发明涉及本文描述的Formula I化合物，以及其药学上可接受的盐，这些化合物作为CRF 1 拮抗剂，在治疗与CRF 1 受体相关的疾病和疾病中起作用，包括与中枢神经系统相关的疾病和疾病。
• Design of 2,5-Dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-<i>a</i>]pyrimidine (NBI 30775/R121919) and Structure−Activity Relationships of a Series of Potent and Orally Active Corticotropin-Releasing Factor Receptor Antagonists
  作者：Chen、Keith M. Wilcoxen、Charles Q. Huang、Yun-Feng Xie、James R. McCarthy、Thomas R. Webb、Yun-Fei Zhu、John Saunders、Xin-Jun Liu、Ta-Kung Chen、Haig Bozigian、Dimitri E. Grigoriadis

  DOI：10.1021/jm040058e

  日期：2004.9.1

  We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF1, receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26h exhibited good binding affinity at the human CRF1 receptor with a K-i value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF1 receptor [IC50 = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells [IC50 = 20 nM). 26h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26h was orally bioavailable and able to penetrate into the brain. 26h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF1, receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26h was developed into a clinical compound and exhibited efficacy in patients with major depression.