[6-(二甲基氨基)-4-甲基-3-吡啶基]乙腈 | 764651-70-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: [6-(二甲基氨基)-4-甲基-3-吡啶基]乙腈
• 中文别名: 6-(N,N-二甲氨基)-4-甲基-3-吡啶基丙腈；7-羟基-8-(3-甲基丁-2-烯-1-基)-2H-色烯-2-酮
• 英文名称: 2-dimethylamino-4-methyl-5-(cyanomethyl)pyridine
• 英文别名: 2-(6-(Dimethylamino)-4-methylpyridin-3-yl)acetonitrile；2-[6-(dimethylamino)-4-methylpyridin-3-yl]acetonitrile
• CAS: 764651-70-9
• 化学式: C₁₀H₁₃N₃
• mdl: MFCD08704357
• 分子量: 175.233
• InChiKey: YEYUOWPIFKOKHW-UHFFFAOYSA-N

物化性质

• 沸点：
  348.3±37.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  6-(二甲基氨基)-4-甲基烟醛	2-dimethylamino-4-methyl-5-formylpyridine	764651-69-6	C9H12N2O	164.207
  N,N,4-三甲基吡啶-2-胺	N,N,4-trimethylpyridin-2-amine	20173-72-2	C8H12N2	136.197

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  1-氰基-1-(6-二甲氨基-4-甲基吡啶-3-基)丙酮	1-cyano-1-(6-dimethylamino-4-methylpyridin-3-yl)acetone	764651-65-2	C12H15N3O	217.271

反应信息

• 作为反应物：
  描述：

  [6-(二甲基氨基)-4-甲基-3-吡啶基]乙腈 在 氢溴酸肼 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 乙腈 为溶剂， 反应 32.0h， 生成 3-(6-(二甲基氨基)-4-甲基吡啶-3-基)-2,5-二甲基-N,N-二丙基吡唑并[1,5-a]嘧啶-7-胺
  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：

  N,N,4-三甲基吡啶-2-胺 在 potassium tert-butylate 、 溴 、 sodium carbonate 、 magnesium 、 1,2-二溴乙烷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 1.67h， 生成 [6-(二甲基氨基)-4-甲基-3-吡啶基]乙腈
  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

文献信息

• Pyrazolo[1,5-Alpha]Pyrimidinyl Derivatives Useful as Corticotropin-Releasing Factor (Crf) Receptor Antagonists
  申请人：Lanier Marion

  公开号：US20080194589A1

  公开（公告）日：2008-08-14

  CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R 1 , R 2a , R 2b , Y, Het, n, o, R 6 , Ar and R 7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，可能在治疗多种疾病方面有用，包括治疗哺乳动物CRF过度分泌引起的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药物学上可接受的盐，酯，溶剂合物，立体异构体和前药，其中R1，R2a，R2b，Y，Het，n，o，R6，Ar和R7如本文所定义。还揭示了含有CRF受体拮抗剂与药学可接受载体组合的组合物，以及使用它们的方法。
• WO2006/44958
  申请人：——

  公开号：——

  公开（公告）日：——
• PYRAZOLO (1,5-ALPHA) PYRIMIDINYL DERIVATIVES USEFUL AS CORTICOTROPIN-RELEASING FACTOR (CRF) RECEPTOR ANTAGONISTS
  申请人：SB Pharmco Puerto Rico Inc.

  公开号：EP1802627A1

  公开（公告）日：2007-07-04
• US7879862B2
  申请人：——

  公开号：US7879862B2

  公开（公告）日：2011-02-01
• [EN] PYRAZOLO [1,5-ALPHA] PYRIMIDINYL DERIVATIVES USEFUL AS CORTICOTROPIN-RELEASING FACTOR (CRF) RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRAZOLO[1,5-ALPHA]PYRIMIDINYLE UTILES COMME ANTAGONISTES VIS-A-VIS DU RECEPTEUR DU FACTEUR DE LIBERATION DE LA CORTICOTROPINE (CRF)
  申请人：SB PHARMCO INC

  公开号：WO2006044958A1

  公开（公告）日：2006-04-27

  [EN] CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R
  [FR] L'invention concerne des antagonistes vis-à-vis du récepteur CRF pouvant être utiles dans le traitement de divers troubles, y compris le traitement des troubles qui se manifestent par une hypersécrétion du CRF chez les mammifères. Les antagonistes ont la structure ci-après (I). Les antagonistes s'entendent aussi des sels, esters, solvates, stéréoisomères et promédicaments pharmaceutiquement acceptables, et pour les besoins de la formule décrite, R< div="">