tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-carboxylate | 1402836-81-0

• 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: tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-carboxylate
• 英文别名: tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidine-1-carboxylate；tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-α]isoindol-5-yl)ethyl)piperidine-1-carboxylate；US10233190, Example 1363；tert-butyl 4-[1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl]piperidine-1-carboxylate
• CAS: 1402836-81-0
• 化学式: C₂₂H₂₉N₃O₃
• 分子量: 383.491
• InChiKey: QYRWUEOAQAHUBN-UHFFFAOYSA-N

物化性质

• 沸点：
  595.2±25.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-carboxylate 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 1-(4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-yl)-2-phenylethan-1-one
  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
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸甲酯 在 甲醇 、 sodium tetrahydroborate 、 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 21.67h， 生成 tert-butyl 4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-carboxylate
  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

• 具有吲哚胺2,3-双加氧酶抑制活性的稠合咪 唑化合物
  申请人：深圳微芯生物科技股份有限公司

  公开号：CN108203438B

  公开（公告）日：2021-09-28

  本发明涉及一类稠合咪唑化合物、其制备方法及其应用。所述化合物的结构如通式I所示，其中各基团的定义如说明书所述。这些化合物能够选择性地抑制吲哚胺2,3‑双加氧酶(IDO)。本发明化合物可作为IDO抑制剂用于治疗和/或预防具有IDO介导的色氨酸代谢途径的病理学特征的疾病，例如癌症、眼部疾病、自身免疫性疾病、心理障碍、抑郁症、焦虑症及其它疾病。
• 稠合咪唑化合物、其制备方法、药物组合物和 用途
  申请人：尚华医药科技(江西)有限公司

  公开号：CN106478634B

  公开（公告）日：2020-05-22

  本发明公开了稠合咪唑化合物、其制备方法、药物组合物和用途。本发明提供了一种如式I所示的稠合咪唑化合物或其药学上可接受的盐。本发明的稠合咪唑化合物是一种IDO和/或TDO抑制剂，可用于制备治疗癌症、病毒感染、抑郁症、神经变性病症、白内障、器官移植排斥和自身免疫等疾病的药物。
• 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。
• FUSED IMIDAZOLE COMPOUND HAVING INDOLEAMINE 2,3-DIOXYGENASE INHIBITORY ACTIVITY
  申请人：Shenzhen Chipscreen Biosciences Co., Ltd.

  公开号：EP3560928A1

  公开（公告）日：2019-10-30

  The invention discloses a type of fused imidazole compound, preparation method and application thereof. The structure of the compound is shown in general formula I. The definition of each group therein is as described in the specification. These compounds are capable of selectively inhibiting indoleamine 2,3-dioxygenase (IDO). The compounds can act as an IDO inhibitor for treating and/or preventing a disease having a pathological feature with IDO-mediated tryptophan metabolic pathways, for example, cancer, eye disease, autoimmune disease, psychological disorder, depression symptom, anxiety disorder and other diseases.

  本发明公开了一种融合咪唑化合物及其制备方法和应用。该化合物的结构如通式 I 所示。其中各基团的定义如说明书所述。这些化合物能够选择性地抑制吲哚胺 2,3-二氧化酶（IDO）。这些化合物可作为 IDO 抑制剂，用于治疗和/或预防具有 IDO 介导的色氨酸代谢途径病理特征的疾病，例如癌症、眼病、自身免疫性疾病、心理障碍、抑郁症状、焦虑症和其他疾病。