IDO-IN-8 | 1402837-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: IDO-IN-8
• 英文别名: (1S,4r)-4-((S)-2-((R)-6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol
• CAS: 1402837-77-7
• 化学式: C₁₈H₂₁FN₂O₂
• 分子量: 316.375
• InChiKey: YGACXVRLDHEXKY-RYPCIWMOSA-N

物化性质

• 沸点：
  555.4±35.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  乙醇：100 mg/mL（316.09 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.28
• 氢给体数：
  2.0
• 氢受体数：
  4.0

安全信息

• 储存条件：
  2-8℃

制备方法与用途

IDO-IN-8 (NLG-1487) 是一种吲哚胺-2,3-双加氧酶(IDO)抑制剂，其IC50值为1-10 μM，更多详细信息可参考专利文献WO2012142237A1中的化合物1487。

反应信息

• 作为产物：
  描述：

  dimethyl 2-(4-(tert-butyldimethylsilyloxy)cyclohexyl)-2-oxoethylphosphonate 在 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氧化碳 、 异丙醇 为溶剂， 反应 8.0h， 生成 IDO-IN-6 、 5H-Imidazo[5,1-a]isoindole-5-ethanol, 6-fluoro-α-(trans-4-hydroxycyclohexyl)-, (αR,5S)- 、 IDO-IN-8 、 IDO-IN-5
  参考文献：
  名称：

  [EN] FUSED IMIDAZOLE DERIVATIVES USEFUL AS IDO INHIBITORS
  [FR] DÉRIVÉS D'IMIDAZOLE FUSIONNÉS POUVANT ÊTRE EMPLOYÉS EN TANT QU'INHIBITEURS D'IDO

  摘要：

  公开号：

  WO2012142237A8

文献信息

• Fused Imidazole Derivatives Useful as IDO Inhibitors
  申请人：NewLink Genetics Corporation

  公开号：US20140066625A1

  公开（公告）日：2014-03-06

  Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleanine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.

  目前提供IDO抑制剂及其制药组合物，用于调节吲哚胺2,3-双加氧酶的活性；治疗吲哚胺2,3-双加氧酶（IDO）介导的免疫抑制；治疗受益于抑制吲哚胺-2,3-双加氧酶酶活性的医疗状况；增强包括给予抗癌药物在内的抗癌治疗的有效性；治疗与癌症相关的肿瘤特异性免疫抑制；以及治疗与传染病相关的免疫抑制。
• COMPOSITIONS COMPRISING FUSED IMIDAZOLE DERIVATIVES USEFUL AS IDO INHIBITORS
  申请人：Newlink Genetics Corporation

  公开号：EP3348558A1

  公开（公告）日：2018-07-18

  Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated inimunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosuppression associated with an infectious disease.

  目前提供的IDO抑制剂及其药物组合物可用于调节吲哚胺-2,3-二氧化酶的活性；治疗吲哚胺-2,3-二氧化酶（IDO）介导的免疫抑制；治疗从抑制吲哚胺-2,3-二氧化酶酶活性中获益的病症；提高抗癌治疗的有效性，包括施用抗癌剂；治疗与癌症相关的肿瘤特异性免疫抑制；以及治疗与传染性疾病相关的免疫抑制。
• IDO inhibitors
  申请人：NewLink Genetics Corporation

  公开号：US10233190B2

  公开（公告）日：2019-03-19

  Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.

  目前提供的 IDO 抑制剂及其药物组合物可用于调节吲哚胺-2,3-二氧 化酶的活性；治疗吲哚胺-2,3-二氧 化酶（IDO）介导的免疫抑制；治疗从抑制吲哚胺-2,3-二氧 化酶酶活性中获益的病症；提高抗癌治疗的有效性，包括施用抗癌剂；治疗与癌症相关的肿瘤特异性免疫抑制；以及治疗与传染病相关的免疫抑制。
• Discovery of Clinical Candidate (1<i>R</i>,4<i>r</i>)-4-((<i>R</i>)-2-((<i>S</i>)-6-Fluoro-5<i>H</i>-imidazo[5,1-<i>a</i>]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1
  作者：Sanjeev Kumar、Jesse P. Waldo、Firoz A. Jaipuri、Agnieszka Marcinowicz、Clarissa Van Allen、James Adams、Tanay Kesharwani、Xiaoxia Zhang、Richard Metz、Angela J. Oh、Seth F. Harris、Mario R. Mautino

  DOI：10.1021/acs.jmedchem.9b00662

  日期：2019.7.25

  A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.
• FUSED IMIDAZOLE DERIVATIVES USEFUL AS IDO INHIBITORS
  申请人：Newlink Genetics Corporation

  公开号：EP2697227B1

  公开（公告）日：2016-02-03