3-cyano-4-{2-(2-methoxyethoxy)ethoxy}benzonitrile | 837371-97-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-cyano-4-{2-(2-methoxyethoxy)ethoxy}benzonitrile
• 英文别名: 4-[2-(2-Methoxyethoxy)ethoxy]benzene-1,3-dicarbonitrile
• CAS: 837371-97-8
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: IXHJTCMHTZONJG-UHFFFAOYSA-N

物化性质

• 沸点：
  415.3±40.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲醇 、 3-cyano-4-{2-(2-methoxyethoxy)ethoxy}benzonitrile 在 sodium methylate 作用下， 生成
  参考文献：
  名称：

  Design, synthesis, and pharmacological and pharmacokinetic evaluation of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives as xanthine oxidoreductase inhibitors

  摘要：

  In an effort to find a potent xanthine oxidoreductase (XO) inhibitor, we discovered the best compound 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]-benzonitrile 28. Here, we describe the following: (1) the design, synthesis, and structure-activity relationship of a series of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives by in vitro studies of XO inhibitory activity in bovine milk and in vivo studies of serum uric acid (UA) reductive activity in rats, (2) a drug interaction study by a cytochrome P450 3A4 (CYP3A4) assay, and (3) a pharmacokinetic (PK) study. Compound 28 exhibits potent XO inhibitory activity, serum UA-lowering activity in rats, weak CYP3A4 inhibitory activity, and moderate PK profile. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.122

文献信息

• Process for producing 1,2,4-triazole compound and intermediate therefor
  申请人：Nakamura Hiroshi

  公开号：US20060189811A1

  公开（公告）日：2006-08-24

  Provided is a process for producing 1,2,4-triazole compound (5), or a salt or hydrate thereof which comprises reacting compound (1) with Rc-X (2) to give compound (3), reacting compound (3) with a nitrilization agent to give compound (4), and then removing the group Rc, as shown by the reaction scheme: (Wherein Ra, Rb and Rd represent a group, Rc represents a group which can be removed by an acid) A 1,2,4-triazole compound (5) having an optionally substituted 2-cyanopyridin-4-yl group at 3-position and an optionally substituted aromatic group at 5-position which inhibits a xanthine oxidase and is useful for treatment of gout and hyperuricemia can be obtained from compound (1) in a high yield without requiring isolation of reaction products in the course of reactions.

  提供一种生产1,2,4-三唑化合物(5)或其盐或水合物的方法，该方法包括将化合物(1)与Rc-X(2)反应得到化合物(3)，将化合物(3)与腈化试剂反应得到化合物(4)，然后去除Rc基团，如下反应方程所示:(其中，Ra、Rb和Rd代表一个基团，Rc代表可以通过酸去除的基团)从化合物(1)中可以高产得到一种1,2,4-三唑化合物(5)，其在3位具有可选取代的2-氰基吡啶-4-基基团，在5位具有可选取代的芳香基团，可以抑制黄嘌呤氧化酶，并且对于痛风和高尿酸血症的治疗有用，而不需要在反应过程中分离反应产物。
• PROCESS FOR PRODUCING 1,2,4-TRIAZOLE COMPOUND AND INTERMEDIATE THEREFOR
  申请人：Fujiyakuhin Co., Ltd.

  公开号：EP1650204A1

  公开（公告）日：2006-04-26

  Provided is a process for producing 1,2,4-triazole compound (5), or a salt or hydrate thereof which comprises reacting compound (1) with Rc-X (2) to give compound (3), reacting compound (3) with a nitrilization agent to give compound (4), and then removing the group Rc, as shown by the reaction scheme: (Wherein Ra, Rb and Rd represent a group, Rc represents a group which can be removed by an acid) A 1,2,4-triazole compound (5) having an optionally substituted 2-cyanopyridin-4-yl group at 3-position and an optionally substituted aromatic group at 5-position which inhibits a xanthine oxidase and is useful for treatment of gout and hyperuricemia can be obtained from compound (1) in a high yield without requiring isolation of reaction products in the course of reactions.

  本发明提供了一种生产 1，2，4-三唑化合物（5）或其盐或水合物的工艺，如反应方案所示，该工艺包括将化合物（1）与 Rc-X (2) 反应得到化合物（3），将化合物（3）与硝化剂反应得到化合物（4），然后除去基团 Rc： (其中 Ra、Rb 和 Rd 代表基团，Rc 代表可被酸去除的基团） 一种 1,2,4-三唑化合物(5)，在 3-位上有一个任选取代的 2-氰基吡啶-4-基团，在 5-位上有一个任选取代的芳香基团，可抑制黄嘌呤氧化酶，可用于治疗痛风和高尿酸血症，可以从化合物(1)高产率地得到，而不需要在反应过程中分离反应产物。
• Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia
  作者：Takahiro Sato、Naoki Ashizawa、Koji Matsumoto、Takashi Iwanaga、Hiroshi Nakamura、Tsutomu Inoue、Osamu Nagata

  DOI：10.1016/j.bmcl.2009.08.091

  日期：2009.11

  Our previous study identified 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-4-pyridyl)-1H-[1,2,4]-triazol-3-yl]-benzonitrile (2) as a safe and potent xanthine oxidoreductase (XOR) inhibitor for the treatment of hyperuricemia. Here, we synthesized a series of 3,5-dipyridyl-1,2,4-triazole derivatives and, in particular, examined their in vivo activity in lowering the serum uric acid levels in rats. As a result, we identified 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole (FYX-051, compound 39) to be one of the most potent XOR inhibitors; it exhibited an extremely potent in vivo activity, weak CYP3A4-inhibitory activity and a better pharmacokinetic pro. le than compound 2. Compound 39 is currently being evaluated in a phase 2 clinical trial. (C) 2009 Elsevier Ltd. All rights reserved.
• EP1650204
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis, and pharmacological and pharmacokinetic evaluation of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives as xanthine oxidoreductase inhibitors
  作者：Takahiro Sato、Naoki Ashizawa、Takashi Iwanaga、Hiroshi Nakamura、Koji Matsumoto、Tsutomu Inoue、Osamu Nagata

  DOI：10.1016/j.bmcl.2008.10.122

  日期：2009.1

  In an effort to find a potent xanthine oxidoreductase (XO) inhibitor, we discovered the best compound 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]-benzonitrile 28. Here, we describe the following: (1) the design, synthesis, and structure-activity relationship of a series of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives by in vitro studies of XO inhibitory activity in bovine milk and in vivo studies of serum uric acid (UA) reductive activity in rats, (2) a drug interaction study by a cytochrome P450 3A4 (CYP3A4) assay, and (3) a pharmacokinetic (PK) study. Compound 28 exhibits potent XO inhibitory activity, serum UA-lowering activity in rats, weak CYP3A4 inhibitory activity, and moderate PK profile. (C) 2008 Elsevier Ltd. All rights reserved.