2-(4-(2-hydroxyethyl)phenyl)isoindoline-1,3-dione | 129051-84-9

• 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: 2-(4-(2-hydroxyethyl)phenyl)isoindoline-1,3-dione
• 英文别名: 2-[4-(2-hydroxyethyl)phenyl]isoindole-1,3-dione
• CAS: 129051-84-9
• 化学式: C₁₆H₁₃NO₃
• 分子量: 267.284
• InChiKey: DZKQUKNAOLKNJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-(2-hydroxyethyl)phenyl)isoindoline-1,3-dione 在 吡啶 、 sodium hydride 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 1-(4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)phenyl)-3-phenylurea
  参考文献：
  名称：

  [EN] IMIDAZOLE DERIVATIVES AS IDO INHIBITORS
  [FR] DÉRIVÉS IMIDAZOLE COMME INHIBITEURS DE L'IDO

  摘要：

  目前提供的是通用结构式（VII）、（VIII）所示的IDO抑制剂及其药物组合物，用于调节色胺酸2,3-二氧化酶的活性；治疗色胺酸2,3-二氧化酶（IDO）介导的免疫抑制；治疗受益于色胺酸-2,3-二氧化酶酶活性抑制的医疗状况；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；以及治疗与传染性疾病相关的免疫抑制。

  公开号：

  WO2011056652A1
• 作为产物：
  描述：

  苯酐 、 4-氨基苯乙醇 以 吡啶 为溶剂， 反应 18.0h， 以48%的产率得到2-(4-(2-hydroxyethyl)phenyl)isoindoline-1,3-dione
  参考文献：
  名称：

  一种新型生物素化同色胺衍生物，用于活细胞中血清素转运蛋白的量子点成像

  摘要：

  5-羟色胺转运蛋白（SERT）是选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药的主要靶点，人们认为该药物通过增加5-羟色胺突触浓度来发挥治疗作用。因此，可用于研究 SERT 细胞运输的探针是有价值的研究工具。我们开发了一种新型配体 (IDT785)，它由 SERT 拮抗剂（四氢吡啶基吲哚衍生物）通过苯乙基接头与生物素化聚乙二醇 (PEG) 缀合组成。该化合物被确定具有生物活性，可抑制 SERT 介导的 IDT307 重摄取，半数抑制浓度为 7.2 ± 0.3 μM。我们证明，IDT785 能够在转染的 HEK-293 培养物中对膜 SERT 进行量子点 (QD) 标记，并且可以使用高亲和力血清素再摄取抑制剂帕罗西汀进行阻断。分子对接研究表明，IDT785 可能与细胞外前庭结合位点而不是正构底物结合位点结合，这可能归因于 PEG 链的亲水性以及渗透到细胞外前庭所需的自由度损失增加。正构结合位点。使用

  DOI：

  10.3389/fncel.2021.667044

文献信息

• Imidazole Derivatives as IDO Inhibitors
  申请人：Mautino Mario R.

  公开号：US20120277217A1

  公开（公告）日：2012-11-01

  Presently provided are IDO inhibitors of general formulae (VII), (VIII) as shown below 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.

  目前提供的是通式（VII），（VIII）所示的IDO抑制剂及其制药组合物，用于调节吲哚胺2,3-二氧化酶的活性；治疗由吲哚胺2,3-二氧化酶（IDO）介导的免疫抑制；治疗受益于抑制吲哚胺2,3-二氧化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。
• Imidazole derivatives as IDO inhibitors
  申请人：Mautino Mario R.

  公开号：US08722720B2

  公开（公告）日：2014-05-13

  Presently provided are IDO inhibitors of general formulae (VII), (VIII) as shown below 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.

  目前提供的是通式（VII）、（VIII）所示的IDO抑制剂及其药物组成物，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；治疗受益于抑制吲哚胺-2,3-二氧化酶酶活性的医学情况；增强包括给予抗癌剂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；以及治疗与传染性疾病相关的免疫抑制。
• Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds To Treat Sickle Cell Disease Symptoms
  作者：Jean Leandro dos Santos、Carolina Lanaro、Lídia Moreira Lima、Sheley Gambero、Carla Fernanda Franco-Penteado、Magna Suzana Alexandre-Moreira、Marlene Wade、Shobha Yerigenahally、Abdullah Kutlar、Steffen E. Meiler、Fernando Ferreira Costa、ManChin Chung

  DOI：10.1021/jm200531f

  日期：2011.8.25

  A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha). Unlike hydroxyurea, the compounds reduced the concentrations of TNF alpha to levels similar to those induced with the control dexamethasone (300 mu mol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.
• Antiplatelet activity and TNF-α release inhibition of phthalimide derivatives useful to treat sickle cell anemia
  作者：Rafael C. Chelucci、Isabela J. de Oliveira、Karina P. Barbieri、Maria E. Lopes-Pires、Marisa C. Polesi、Diego E. Chiba、Iracilda Z. Carlos、Sisi Marcondes、Jean L. Dos Santos、ManChin Chung

  DOI：10.1007/s00044-019-02371-z

  日期：2019.8

  Sickle Cell Anemia (SCA) is one of the most prevalent hereditary hematological diseases worldwide. The disease is characterized by chronic inflammation, hypercoagulable state, and pro-thrombotic profile, which lead the vaso-occlusive process. In this work, we described the antiplatelet activity and the ability to reduce tumor necrosis factor-alpha (TNF-) levels of phthalimide derivatives. All compounds inhibited platelet aggregation induced by collagen and adenosine diphosphate, at levels ranging from 26.0 to 74.2% and 30.7 to 79.6%, respectively. The compounds exhibited reduced bleeding time compared to acetylsalicylic acid (ASA). Moreover, compounds 4c and 10c inhibited TNF- levels at 73.5% and 65.0%, respectively. These findings suggest that phthalimide derivatives 4c and 10c are promising lead compounds useful to prevent vaso-occlusion and inflammation associated with the sickle cell anemia.[GRAPHICS].
• Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (<i>S</i>)-Citalopram
  作者：Vivek Kumar、Nageswari Yarravarapu、David J. Lapinsky、Danielle Perley、Bruce Felts、Michael J. Tomlinson、Roxanne A. Vaughan、L. Keith Henry、John R. Lever、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.5b00682

  日期：2015.7.23

  Three photoaffinity ligands (PALs) for the human serotonin transporter (hSERT) were synthesized based on the selective serotonin reuptake inhibitor (SSRI), (S)-citalopram (1). The classic 4-azido-3-iodo-phenyl group was appended to either the C-1 Or C-5 position of the parent molecule, with variable-length linkers, to generate ligands 15, 22, and 26: These ligands retained high to moderate affinity binding (K-i = 24-227 nM) for hSERT, as assessed by [H-3]5-HT transport inhibition. When tested against Ser438Thr hSERT, all three PALs showed dramatic rightward shifts in inhibitory potency, with K-i values ranging from 3.8 to 9.9 mu M, consistent with the role of Ser438 as a key residue for high-affinity binding of many SSRIs, including (S)-citalopram. Photoactivation studies demonstrated irreversible adduction to hSERT by all ligands, but the reduced (S)-citalopram inhibition of labeling by [I-125]15 compared to that by [I-125]22 and [I-125]26 suggests differences in binding mode(s). These radioligands will be useful for characterizing the drug protein binding interactions for (S)-citalopram at hSERT.