dimethyl (2-(1-acetylpiperidin-4-yl)-2-oxoethyl)phosphonate | 1402838-51-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: dimethyl (2-(1-acetylpiperidin-4-yl)-2-oxoethyl)phosphonate
• 英文别名: 1-(1-Acetylpiperidin-4-yl)-2-dimethoxyphosphorylethanone；1-(1-acetylpiperidin-4-yl)-2-dimethoxyphosphorylethanone
• CAS: 1402838-51-0
• 化学式: C₁₁H₂₀NO₅P
• 分子量: 277.257
• InChiKey: KGGHGNCAAOOWID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl (2-(1-acetylpiperidin-4-yl)-2-oxoethyl)phosphonate 、 NLG-919中间体 在 甲醇 、 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 19.67h， 生成 1-(4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-yl)ethanone
  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：

  1-acetyl-piperidine-4-carboxylic acid methyl ester 、 甲基膦酸二甲酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 以64%的产率得到dimethyl (2-(1-acetylpiperidin-4-yl)-2-oxoethyl)phosphonate
  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

• 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。
• 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：EP2697227B1

  公开（公告）日：2016-02-03
• 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.
• US9260434B2
  申请人：——

  公开号：US9260434B2

  公开（公告）日：2016-02-16