4-(2-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol | 1402836-86-5

• 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: 4-(2-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol
• 英文别名: 4-(2-(6-fluoro-5H-imidazo[5,1-α]isoindol-5-yl)-1-hydroxyethyl)cyclohexanol；5H-Imidazo[5,1-a]isoindole-5-ethanol, 6-fluoro-alpha-(trans-4-hydroxycyclohexyl)-；4-[2-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl]cyclohexan-1-ol
• CAS: 1402836-86-5
• 化学式: C₁₈H₂₁FN₂O₂
• 分子量: 316.375
• InChiKey: YGACXVRLDHEXKY-UHFFFAOYSA-N

物化性质

• 沸点：
  555.4±35.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  存储条件：2-8°C，干燥，密闭。

反应信息

• 作为反应物：
  描述：

  4-(2-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol 在 AD-H column 作用下， 以 二氧化碳 、 异丙醇 为溶剂， 生成 IDO-IN-5 、 5H-Imidazo[5,1-a]isoindole-5-ethanol, 6-fluoro-α-(trans-4-hydroxycyclohexyl)-, (αR,5S)- 、 IDO-IN-8 、 IDO-IN-6
  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
• 作为产物：
  描述：

  2-氟-6-(1-三苯甲基-1H-咪唑-4-基)苯甲醛 在 盐酸 、 甲醇 、 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 21.67h， 生成 4-(2-(6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol
  参考文献：
  名称：

  Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.9b00662

文献信息

• [EN] TANK-BINDING KINASE INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE KINASES SE LIANT À TANK
  申请人：GILEAD SCIENCES INC

  公开号：WO2015187684A1

  公开（公告）日：2015-12-10

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  揭示了具有以下化学式（I）的化合物及其使用和制备方法。
• TANK-BINDING KINASE INHIBITOR COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：US20160096827A1

  公开（公告）日：2016-04-07

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  具有以下化学式（I）的化合物以及它们的使用和制备方法已被披露：
• Stereoselective Synthesis of the IDO Inhibitor Navoximod
  作者：Frédéric St-Jean、Rémy Angelaud、Stephan Bachmann、Diane E. Carrera、Travis Remarchuk、Katarzyna A. Piechowicz、Katrin Niedermann、Hans Iding、Roland Meier、Haiyun Hou、Lauren E. Sirois、Jie Xu、Martin Olbrich、Pankaj Rege、Maud Guillemot-Plass、Francis Gosselin

  DOI：10.1021/acs.joc.1c02994

  日期：2022.4.1

  A highly efficient asymmetric synthesis of the IDO inhibitor navoximod, featuring the stereoselective installation of two relative and two absolute stereocenters from an advanced racemic intermediate, is described. The stereocenters were set via a crystallization-induced dynamic resolution along with two selective ketone reductions: one via a biocatalytic ketoreductase transformation and one via substrate-controlled

  描述了 IDO 抑制剂 navoximod 的高效不对称合成，其特点是从先进的外消旋中间体中立体选择性安装两个相对和两个绝对立体中心。立体中心是通过结晶诱导的动态分辨率以及两种选择性的酮还原来设定的：一种是通过生物催化酮还原酶转化，另一种是通过 LiAlH(O t- Bu) 3的底物控制的氢化物递送。按照这一策略，从 2-氟苯甲醛分 10 个步骤合成了 navoximod，并以 23% 的总产率和 99.7% 的 ee 和高纯度分离。
• 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。