1-cyclohexyl-2-(5H-imidazo[5,1-α]isoindol-5-yl)propan-1-ol | 1402837-08-4

• 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: 1-cyclohexyl-2-(5H-imidazo[5,1-α]isoindol-5-yl)propan-1-ol
• 英文别名: US10233190, Example 1400；1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)propan-1-ol
• CAS: 1402837-08-4
• 化学式: C₁₉H₂₄N₂O
• 分子量: 296.412
• InChiKey: LXUFCLWCRAGUAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-cyclohexyl-2-(5H-imidazo[5,1-α]isoindol-5-yl)propan-1-ol 在 二乙醇胺 作用下， 以 正己烷 、 醋酸异丙酯 为溶剂， 生成 (1R,2S)-1-cyclohexyl-2-((S)-5H-imidazo[5,1-a]isoindol-5-yl)propan-1-ol
  参考文献：
  名称：

  Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors

  摘要：

  A class of imidazoisoindole (III) heme-binding indoleamine-2,3-dioxygenase (IDO1) inhibitors were optimized via structure-based drug design into a series of tryptophan-2,3-dioxygenase (TDO)-selective inhibitors. Kynurenine pathway modulation was demonstrated in vivo, which enabled evaluation of TDO as a potential cancer immunotherapy target. As means of mitigating the risk of drug-drug interactions arising from cytochrome P450 inhibition, a novel property-based drug design parameter, herein referred to as the CYP Index, was implemented for the design of inhibitors with appreciable selectivity for TDO over CYP3A4. We anticipate the CYP Index will be a valuable design parameter for optimizing CYP inhibition of any small molecule inhibitor containing a Lewis basic motif capable of binding heme.

  DOI：

  10.1021/acsmedchemlett.0c00004
• 作为产物：
  描述：

  环己基甲乙酮 在 甲醇 、 sodium tetrahydroborate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 1-cyclohexyl-2-(5H-imidazo[5,1-α]isoindol-5-yl)propan-1-ol
  参考文献：
  名称：

  Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors

  摘要：

  A class of imidazoisoindole (III) heme-binding indoleamine-2,3-dioxygenase (IDO1) inhibitors were optimized via structure-based drug design into a series of tryptophan-2,3-dioxygenase (TDO)-selective inhibitors. Kynurenine pathway modulation was demonstrated in vivo, which enabled evaluation of TDO as a potential cancer immunotherapy target. As means of mitigating the risk of drug-drug interactions arising from cytochrome P450 inhibition, a novel property-based drug design parameter, herein referred to as the CYP Index, was implemented for the design of inhibitors with appreciable selectivity for TDO over CYP3A4. We anticipate the CYP Index will be a valuable design parameter for optimizing CYP inhibition of any small molecule inhibitor containing a Lewis basic motif capable of binding heme.

  DOI：

  10.1021/acsmedchemlett.0c00004

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。
• FUSED IMIDAZOLE DERIVATIVES USEFUL AS IDO INHIBITORS
  申请人：Newlink Genetics Corporation

  公开号：EP2697227A1

  公开（公告）日：2014-02-19
• IDO Inhibitors
  申请人：NewLink Genetics Corporation

  公开号：US20160362412A1

  公开（公告）日：2016-12-15

  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.