9-methyl-<9H>-pyrido<2,3-b>indole-3-carbonitrile | 139884-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 9-methyl-<9H>-pyrido<2,3-b>indole-3-carbonitrile
• 英文别名: 9-methyl-9H-pyrido[2,3-b]indole-3-carbonitrile；9-Methyl-9H-pyrido[2,3-B]indole-3-carbonitrile；9-methylpyrido[2,3-b]indole-3-carbonitrile
• CAS: 139884-24-5
• 化学式: C₁₃H₉N₃
• 分子量: 207.235
• InChiKey: DDBFCHTZWJEDSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-methyl-<9H>-pyrido<2,3-b>indole-3-carbonitrile 在 sodium tetrahydroborate 、 二异丁基氢化铝 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 1.5h， 生成 (9-methyl-9H-pyrido[2,3-b]indol-3-yl)methanol
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I

  摘要：

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.054
• 作为产物：
  描述：

  2-氨基吲哚 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 9-methyl-<9H>-pyrido<2,3-b>indole-3-carbonitrile
  参考文献：
  名称：

  苯并噻吩并[2,3-b]吡啶和吡咯并[2,3-b]吲哚系列的退火NADH模型的合成

  摘要：

  合成了苯并噻吩并[2,3-b]吡啶和吡啶并[2,3-b]吲哚系列的NADH模型。合成的关键步骤是适当的吲哚或苯并噻吩胺与被掩盖的1,3-二羰基化合物之间的闭环反应。此方法提供了四个新的退火NADH模型。这些模型中的一个允许使用NADH模型进行苯乙酮的首次制备还原。

  DOI：

  10.1016/s0040-4020(01)88187-4

文献信息

• Synthesis of annelated NADH models in Benzothieno[2,3-b]pyridine and Pyridol[2,3-b]indole Series
  作者：Vincent Levacher、Nadjib Boussad、Georges Dupas、Jean Bourguignon、Guy Quéguiner

  DOI：10.1016/s0040-4020(01)88187-4

  日期：——

  NADH models in the benzothieno[2,3-b]pyridine and pyridol[2,3-b]indole series have been synthesized. The key step of the synthesis is the ring closure reaction between the appropriate indole or benzothiophene amines and a masked 1,3-dicarbonyl compound. This method afforded four new annelated NADH models. One of these models allowed the first preparative reduction of acetophenone with a NADH model

  合成了苯并噻吩并[2,3-b]吡啶和吡啶并[2,3-b]吲哚系列的NADH模型。合成的关键步骤是适当的吲哚或苯并噻吩胺与被掩盖的1,3-二羰基化合物之间的闭环反应。此方法提供了四个新的退火NADH模型。这些模型中的一个允许使用NADH模型进行苯乙酮的首次制备还原。
• Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I
  作者：Sanjib Das、Rajendra L. Harde、Dnyaneshwar E. Shelke、Neelima Khairatkar-Joshi、Malini Bajpai、Ratika S. Sapalya、Harshada V. Surve、Girish S. Gudi、Rambabu Pattem、Dayanidhi B. Behera、Satyawan B. Jadhav、Abraham Thomas

  DOI：10.1016/j.bmcl.2014.03.054

  日期：2014.5

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.