3-(naphthalen-1-yl)pyrrolidine-2,5-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(naphthalen-1-yl)pyrrolidine-2,5-dione
• 英文别名: 3-naphthalen-1-ylpyrrolidine-2,5-dione
• 化学式: C₁₄H₁₁NO₂
• 分子量: 225.247
• InChiKey: BYBZLRMZLUGIDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-萘乙腈 在 sodium hydroxide 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 3-(naphthalen-1-yl)pyrrolidine-2,5-dione
  参考文献：
  名称：

  Synthesis of 3-Methylthio-4-aryl-3-pyrroline-2,5-diones and 3-Arylpyrrolidine-2,5-diones by Reaction of Nitroketene Dithioacetal with Arylacetonitriles

  摘要：

  The reaction of nitroketene dithioacetal (1a), i.e., 2,2-bis(methylthio)-1-nitroethylene, with arylacetonitriles (2a-I) in the presence of the base like sodium hydroxide gave 4-nitrobut-2-enenitriles (3a-I) which were converted into 5-hydroxyimino-4-methylthio-3-phenyl-3-pyrrolin-2-ones (4a-i) under refluxing in methanol. Title compounds (5a-i) were readily obtained by the treatment of 4a-i with hydrochloric acid and were finally led to N-methylated products (6a-I) with methyl iodide. The reduction of maleimides (4-6) with zinc dust in acetic acid afforded the corresponding 3-arylpyrrolidine-2,5-diones (7a-i) that can be converted to pharmacologycally active compounds like mesembrines.

  DOI：

  10.3987/com-01-9336

文献信息

• PYRROLIDINE-2, 5-DIONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE AS IDO1 INHIBITORS
  申请人：ITEOS THERAPEUTICS

  公开号：US20150329525A1

  公开（公告）日：2015-11-19

  The present invention relates to compound of Formula I or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula I as IDO1 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer and endometriosis. The invention also relates to a process for manufacturing compounds of Formula I.

  本发明涉及公式I的化合物或其药学上可接受的对映体、盐、溶剂合物或前药。该发明进一步涉及将公式I的化合物用作IDO1抑制剂的用途。该发明还涉及将公式I的化合物用于治疗和/或预防癌症和子宫内膜异位症的用途。该发明还涉及一种制造公式I化合物的方法。
• Discovery of a Novel and Selective Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1<i>H</i>-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate
  作者：Stefano Crosignani、Patrick Bingham、Pauline Bottemanne、Hélène Cannelle、Sandra Cauwenberghs、Marie Cordonnier、Deepak Dalvie、Frederik Deroose、Jun Li Feng、Bruno Gomes、Samantha Greasley、Stephen E Kaiser、Manfred Kraus、Michel Négrerie、Karen Maegley、Nichol Miller、Brion W Murray、Manfred Schneider、James Soloweij、Albert E Stewart、Joseph Tumang、Vince R Torti、Benoit Van Den Eynde、Martin Wythes

  DOI：10.1021/acs.jmedchem.7b00974

  日期：2017.12.14

  oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure–activity relationship around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode. Clinical candidate 6 shows

  肿瘤使用色氨酸分解酶，例如吲哚胺2，3-二加氧酶（IDO-1）来诱导免疫抑制环境。IDO-1响应炎症刺激而被诱导，并通过效应T细胞无反应性和增强的Treg功能促进免疫耐受。因此，IDO-1是诱导关键免疫抑制机制的纽带，并代表肿瘤学中重要的免疫治疗靶标。从HTS 5开始，已开发出IDO-1抑制剂6（EOS200271 / PF-06840003）。周围的结构-活性关系6中描述和合理化使用的X射线晶体结构6结合人IDO-1，这表明6与迄今为止描述的大多数IDO-1抑制剂不同，它不与血红素铁原子结合，并具有新颖的结合方式。临床候选药物6在IDO-1人全血检测中显示出良好的功效，并且还显示出非常有利的ADME谱，从而导致有利的预期人药代动力学特性，包括16-19 h的预期半衰期。
• Selective and tunable synthesis of 3-arylsuccinimides and 3-arylmaleimides from arenediazonium tetrafluoroborates and maleimides
  作者：Zhen-Hua Yang、Zhong-Hui Chen、Yu-Long An、Sheng-Yin Zhao

  DOI：10.1039/c6ra00136j

  日期：——

  arenediazonium tetrafluoroborates and maleimides in the presence of TiCl3. The reactions generated 3-arylsuccinimides in satisfactory yields under mild reaction conditions. In addition, 3-arylmaleimides were obtained by the coupling of arenediazonium tetrafluoroborate and maleimides catalyzed by CuCl. This methodology provided the selective and tunable synthesis of two classes of products by simply

  用于合成3- arylsuccinimides A高效合成策略已经从芳基重氮四氟硼酸盐和马来酰亚胺开发的TiCl的存在3。在温和的反应条件下，反应以令人满意的产率产生了3-芳基琥珀酰亚胺。另外，通过四氟硼酸壬二唑鎓与CuCl催化的马来酰亚胺的偶联，获得了3-芳基马来酰亚胺。通过简单地切换不同的金属试剂，该方法提供了两类产品的选择性和可调谐合成。该方法简单，高效，实用。
• [EN] PYRROLIDINE-2,5-DIONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE AS IDO1 INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLIDINE -2,5-DIONE, COMPOSITIONS PHARMACEUTIQUES ET PROCÉDÉS POUR UNE UTILISATION EN TANT QU'INHIBITEURSDE DE IDO1
  申请人：ITEOS THERAPEUTICS

  公开号：WO2015173764A1

  公开（公告）日：2015-11-19

  The present invention relates to compound of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) as ID01 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer and endometriosis. The invention also relates to a process for manufacturing compounds of Formula (I).

  本发明涉及一种式（I）的化合物或其药学上可接受的对映体、盐、溶剂物或前药。本发明还涉及将式（I）的化合物用作ID01抑制剂的用途。本发明还涉及将式（I）的化合物用于治疗和/或预防癌症和子宫内膜异位症的用途。本发明还涉及一种制造式（I）化合物的方法。
• Treatment method utilizing pyrrolidine-2, 5-dione derivatives as IDO1 inhibitors
  申请人：ITEOS THERAPEUTICS

  公开号：US10398679B2

  公开（公告）日：2019-09-03

  Uses of compound of Formula I: or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof are described. The compounds of Formula I are useful as IDO1 inhibitors. These are also useful for the treatment and/or prevention of cancer and endometriosis.

  式 I 化合物的用途 或其药学上可接受的对映体、盐、溶液剂或原药。式 I 的化合物可用作 IDO1 抑制剂。这些化合物还可用于治疗和/或预防癌症和子宫内膜异位症。