1H-indole-2-carboxylic acid pyridin-3-ylamide | 182121-53-5

• 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: 1H-indole-2-carboxylic acid pyridin-3-ylamide
• 英文别名: N-(pyridin-3-yl)-1H-indole-2-carboxamide；N-pyridin-3-yl-1H-indole-2-carboxamide
• CAS: 182121-53-5
• 化学式: C₁₄H₁₁N₃O
• mdl: MFCD12533655
• 分子量: 237.261
• InChiKey: NLOUPEPYUGRKHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  吲哚-2-羧酸 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 1H-indole-2-carboxylic acid pyridin-3-ylamide
  参考文献：
  名称：

  Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC50 values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.032

文献信息

• [EN] INDOLE DERIVATIVES FOR USE IN MEDICINE<br/>[FR] DÉRIVÉS INDOLÉS DESTINÉS À ÊTRE UTILISÉS DANS LE DOMAINE DE LA MÉDECINE
  申请人：IOMET PHARMA LTD

  公开号：WO2015150097A1

  公开（公告）日：2015-10-08

  Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X1, X2, X3, X4, and X5 may be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom are maintained; each R1, R2, R3, R4, R5, and R7 may be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X1, X2, X3, X4, and X5 are maintained; one or two R6 groups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of R6 groups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one R6 is an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an α-, β-, or γ-position to the carbon atom to which the R6 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom.

  提供了一种色氨酸2,3-双加氧酶（TDO）和/或吲哚酮-2,3-双加氧酶（IDO）抑制剂化合物，用于医学，该化合物包括以下结构式：其中X1、X2、X3、X4和X5可以相同或不同，并且每个独立地选择自C、N和O；每个有点线的原子可以独立地具有双键或单键，前提是保持每个原子的价；每个R1、R2、R3、R4、R5和R7可以存在或不存在，并且可以相同或不同，并且选择自H和取代或未取代的有机基团，前提是存在这样的R基团的数量使得X1、X2、X3、X4和X5的价被保持；可以存在一个或两个R6基团，并且选择自H和取代或未取代的有机基团，前提是存在这样的R6基团的数量使得它们附着的碳原子的价被保持，并且前提是至少有一个R6是包含一个与氧原子双键的原子的有机基团（优选为一个羰基基团或一个磺酰基基团），在其中与氧原子双键的原子也与一个杂原子键合。
• INDOLE DERIVATIVES FOR USE IN MEDICINE
  申请人：IOMet Pharma Ltd.

  公开号：US20190084933A1

  公开（公告）日：2019-03-21

  Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X 1 , X 2 , X 3 , X 4 , and X 5 may be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom arc maintained; each R 1 , R 2 , R 3 , R 4 , and R 7 may be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X 1 , X 2 , X 3 , X 4 , and X 5 are maintained; one or two R 6 groups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of R 6 groups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one R 6 is an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an α-, β-, or γ-position to the carbon atom to which the R 6 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom.

  提供一种色氨酸-2,3-双加氧酶（TDO）和/或吲哚胺-2,3-双加氧酶（IDO）抑制剂化合物，用于医学，该化合物包括以下式子：其中X1、X2、X3、X4和X5可以相同或不同，并且每个独立地选择自C、N和O；每个有点线的原子可以独立地具有双键或单键，前提是每个原子的价被保持；每个R1、R2、R3、R4和R7可以存在或不存在，可以相同或不同，并且选择自H和取代或未取代的有机基团，前提是存在的这些R基团的数量使得X1、X2、X3、X4和X5的价被保持；可以存在一或两个R6基团，选择自H和取代或未取代的有机基团，前提是存在的这些R6基团的数量使得它们附着的碳原子的价被保持，并且至少有一个R6是包含一个双键连接到α-、β-或γ-位置的氧原子（优选为羰基基团或磺酰基团）的有机基团，并且其中双键连接到氧原子的原子也与杂原子相结合。
• Indole derivatives for use in medicine
  申请人：IOmet Pharma Ltd.

  公开号：US10167257B2

  公开（公告）日：2019-01-01

  Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X1, X2, X3, X4, and X5 may be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom are maintained; each R1, R2, R3, R4, R5, and R7 may be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X1, X2, X3, X4, and X5 are maintained; one or two R6 groups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of R6 groups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one R6 is an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an α-, β-, or γ-position to the carbon atom to which the R6 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom.

  本发明提供了一种用于医药的色氨酸-2,3-二氧化酶（TDO）和/或吲哚胺-2,3-二氧化酶（IDO）抑制剂化合物，该化合物包括下式：其中 X1、X2、X3、X4 和 X5 可以相同或不同，且各自独立地选自 C、N 和 O；每个带有虚线的原子可以独立地具有双键或单键，前提是每个原子上的价保持不变；每个 R1、R2、R3、R4、R5 和 R7 可以存在或不存在，可以相同或不同，并且可以选自 H 和取代或未取代的有机基团，条件是存在的此类 R 基团的数目使得 X1、X2、X3、X4 和 X5 的化合价保持不变；可存在一个或两个 R6 基团，它们选自 H 和一个取代或未取代的有机基团，条件是所存在的 R6 基团的数目必须保证它们所连接的碳原子的价保持不变、且至少有一个 R6 是有机基团，该有机基团包含一个与氧原子（最好是羰基或磺酰基）在与 R6 所连接的碳原子的 α-、β- 或 γ- 位置上双键结合的原子，其中与氧原子双键结合的原子还与杂原子结合。
• Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
  作者：Eduard Dolušić、Pierre Larrieu、Sébastien Blanc、Frédéric Sapunaric、Jenny Pouyez、Laurence Moineaux、Delphine Colette、Vincent Stroobant、Luc Pilotte、Didier Colau、Thierry Ferain、Graeme Fraser、Moreno Galleni、Jean-Marie Frère、Bernard Masereel、Benoît Van den Eynde、Johan Wouters、Raphaël Frédérick

  DOI：10.1016/j.ejmech.2011.02.049

  日期：2011.7

  Indoleamine 2,3-dioxygenase (IDO) is an important new therapeutic target for the treatment of cancer. With the aim of discovering novel IDO inhibitors, a virtual screen was undertaken and led to the discovery of the keto-indole derivative 1a endowed with an inhibitory potency in the micromolar range. Detailed kinetics were performed and revealed an uncompetitive inhibition profile. Preliminary SARs were drawn in this series and corroborated the putative binding orientation as suggested by docking. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
  作者：Eduard Dolušić、Pierre Larrieu、Sébastien Blanc、Frédéric Sapunaric、Bernadette Norberg、Laurence Moineaux、Delphine Colette、Vincent Stroobant、Luc Pilotte、Didier Colau、Thierry Ferain、Graeme Fraser、Moreno Galeni、Jean-Marie Frère、Bernard Masereel、Benoît Van den Eynde、Johan Wouters、Raphaël Frédérick

  DOI：10.1016/j.bmc.2010.12.032

  日期：2011.2

  Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC50 values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results. (C) 2010 Elsevier Ltd. All rights reserved.