5-[(5-hydroxy-2-oxo-1,2-dihydro-3H-indol-(3Z)-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid N-[2-(diethylamino)ethyl]amide | 1126899-61-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-[(5-hydroxy-2-oxo-1,2-dihydro-3H-indol-(3Z)-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid N-[2-(diethylamino)ethyl]amide
• 英文别名: 5-hydroxyl sunitinib；5-hydroxysunitinib；5-[5-hydroxy-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)-amide；Sunitinib metabolite M8；N-[2-(diethylamino)ethyl]-5-[(Z)-(5-hydroxy-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
• CAS: 1126899-61-3
• 化学式: C₂₂H₂₈N₄O₃
• 分子量: 396.489
• InChiKey: YBNMTJYLJWAMGJ-ATVHPVEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.5
• 氢给体数：
  4
• 氢受体数：
  4

制备方法与用途

PHA-782584是舒尼替尼的代谢产物。舒尼替尼是一种口服的多靶点酪氨酸激酶抑制剂，具有抗肿瘤活性[1]。

反应信息

• 作为反应物：
  描述：

  5-[(5-hydroxy-2-oxo-1,2-dihydro-3H-indol-(3Z)-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid N-[2-(diethylamino)ethyl]amide 在 4-二甲氨基吡啶 、 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 为溶剂， 反应 50.0h， 生成 (2S)-1-{[(2S)-1-{[(3Z)-3-[(4-{[2-(Diethylamino)ethyl]carbamoyl}-3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl]oxy}-1-oxopropan-2-yl]oxy}-1-oxopropan-2-yl (2S)-2-hydroxypropanoate
  参考文献：
  名称：

  Compounds And Compositions for the Treatment of Ocular Disorders

  摘要：

  该披露描述了前药和前列腺素的衍生物、碳酸酐酶抑制剂、激酶抑制剂、β-肾上腺素受体拮抗剂和其他药物，以及含有这些前药和衍生物的受控释放配方，用于治疗眼部疾病。

  公开号：

  US20170080092A1
• 作为产物：
  描述：

  2-甲基-6-喹啉甲酸 、 N-(2-(二乙基氨基)乙基)-5-甲酰基-2,4-二甲基-1H-吡咯-3-甲酰胺 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以61%的产率得到5-[(5-hydroxy-2-oxo-1,2-dihydro-3H-indol-(3Z)-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid N-[2-(diethylamino)ethyl]amide
  参考文献：
  名称：

  Compounds And Compositions for the Treatment of Ocular Disorders

  摘要：

  该披露描述了前药和前列腺素的衍生物、碳酸酐酶抑制剂、激酶抑制剂、β-肾上腺素受体拮抗剂和其他药物，以及含有这些前药和衍生物的受控释放配方，用于治疗眼部疾病。

  公开号：

  US20170080092A1

文献信息

• [EN] DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TROUBLES OCULAIRES
  申请人：GRAYBUG VISION INC

  公开号：WO2018175922A1

  公开（公告）日：2018-09-27

  The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.

  本发明提供了治疗活性化合物的新前药，包括寡聚前药，以及用于治疗医学疾病的组合物，例如青光眼，一种与眼压增高有关的疾病或异常，需要神经保护的疾病，年龄相关性黄斑变性，或糖尿病性视网膜病变。
• Extended release microparticles and suspensions thereof for medical therapy
  申请人：Graybug Vision, Inc.

  公开号：US11160870B2

  公开（公告）日：2021-11-02

  An improved microparticle or lyophilized or otherwise reconstitutable microparticle composition thereof for medical therapy, including ocular therapy.

  一种用于医疗（包括眼科治疗）的改良微粒或冻干或可重组微粒组合物。
• Synthesis, in silico, in vitro, and in vivo investigation of 5-[11C]methoxy-substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2
  作者：Julio Caballero、Camila Muñoz、Jans H. Alzate-Morales、Susana Cunha、Lurdes Gano、Ralf Bergmann、Joerg Steinbach、Torsten Kniess

  DOI：10.1016/j.ejmech.2012.10.020

  日期：2012.12

  Sunitinib (R) (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels in tumor tissue giving valuable information for anti-angiogenic therapy. Herein we report the synthesis of 5-methoxy-sunitinib 5 and its C-11-radiolabeled analog [C-11]-5. The non-radioactive reference compound 5 was prepared by Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. A binding constant (K-d) of 20 nM for 5 was determined by competition binding assay against VEGFR-2. In addition, the binding mode of sunitinib (R) and its 5-methoxy substituted derivative was studied by flexible docking simulations. These studies revealed that the substitution of the fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect the inhibitor orientation, but affected the electrostatic and van der Waals interactions of the ligand with residues near the DFG motif of VEGFR-2. 5-[C-11]methoxy-sunitinib ([C-11]-5) was synthesized by reaction of the desmethyl precursor with [C-11]CH3I in the presence of DMF and NaOH in 17 +/- 3% decay-corrected radiochemical yield at a specific activity of 162-205 GBq/mu mol (EOS). In vivo stability studies of [C-11]-5 in rat blood showed that more than 70% of the injected compound was in blood stream, 60 min after administration. (c) 2012 Elsevier Masson SAS. All rights reserved.
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
  申请人：Graybug Vision, Inc.

  公开号：US20180028673A1

  公开（公告）日：2018-02-01

  The disclosure describes prodrugs and derivatives of prostaglandins, carbonic anhydrase inhibitors, kinase inhibitors, beta-adrenergic receptor antagonists and other drugs, as well as controlled delivery formulations containing such prodrugs and derivatives, for the treatment of ocular disorders.
• DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
  申请人：Graybug Vision, Inc.

  公开号：US20200031783A1

  公开（公告）日：2020-01-30

  The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.