2-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-1-(3-(isopropylamino)propyl)-1H-imidazo[4,5-c]pyridin-4-amine | 1061317-59-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-1-(3-(isopropylamino)propyl)-1H-imidazo[4,5-c]pyridin-4-amine
• 英文别名: 2-(6-Iodobenzo[d][1,3]dioxol-5-ylthio)-1-(3-(isopropylamino)propyl)-1h-imidazo[4,5-c]pyridin-4-amine；2-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-1-[3-(propan-2-ylamino)propyl]imidazo[4,5-c]pyridin-4-amine
• CAS: 1061317-59-6
• 化学式: C₁₉H₂₂IN₅O₂S
• 分子量: 511.386
• InChiKey: FNNXIVAECASPAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-1-(4-methoxybenzyl)-1H-imidazo[4,5-c]pyridin-4-amine 在 caesium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 2-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-1-(3-(isopropylamino)propyl)-1H-imidazo[4,5-c]pyridin-4-amine
  参考文献：
  名称：

  Structure–Activity Relationship in a Purine-Scaffold Compound Series with Selectivity for the Endoplasmic Reticulum Hsp90 Paralog Grp94

  摘要：

  Grp94 is involved in the regulation of a restricted number of proteins and represents a potential target in a host of diseases, including cancer, septic shock, autoimmune diseases, chronic inflammatory conditions, diabetes, coronary thrombosis, and stroke. We have recently identified a novel allosteric pocket located in the Grp94 N-terminal binding site that can be used to design ligands with a 2-log selectivity over the other Hsp90 paralogs. Here we perform extensive SAR investigations in this ligand series and rationalize the affinity and paralog selectivity of choice derivatives by molecular modeling. We then use this to design 18c, a derivative with good potency for Grp94 (IC50 = 0.22 mu M) and selectivity over other paralogs (>100- and 33-fold for Hsp90 alpha/beta and Trap-1, respectively). The paralog selectivity and target-mediated activity of 18c was confirmed in cells through several functional readouts. Compound 18c was also inert when tested against a large panel of kinases. We show that 18c has biological activity in several cellular models of inflammation and cancer and also present here for the first time the in vivo profile of a Grp94 inhibitor.

  DOI：

  10.1021/acs.jmedchem.5b00197

文献信息

• FUSED AMINO PYRIDINE AS HSP90 INHIBITORS
  申请人：Cai Xiong

  公开号：US20080234314A1

  公开（公告）日：2008-09-25

  The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.

  本发明涉及含有融合氨基吡啶核的HSP90抑制剂，可用作HSP90的抑制剂，以及它们在治疗HSP90相关疾病和紊乱，如癌症、自身免疫疾病或神经退行性疾病中的用途。
• Fused amino pyridine as HSP90 inhibitors
  申请人：Curis, Inc.

  公开号：US10035797B2

  公开（公告）日：2018-07-31

  The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.

  本发明涉及含有融合氨基吡啶核心的 HSP90 抑制剂，这些抑制剂可用作 HSP90 的抑制剂，并可用于治疗与 HSP90 相关的疾病，如癌症、自身免疫性疾病或神经退行性疾病。
• HSP90-targeted cardiac imaging and therapy
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US10201623B2

  公开（公告）日：2019-02-12

  The present invention provides new methods for cardiac imaging and related medical applications thereof. In some embodiments, the present invention provides a method for the diagnosis of cardiovascular diseases, conditions, or disorders. In some embodiments, the present invention provides a method for the treatment or prevention of cardiovascular diseases, conditions, or disorders. In some embodiments, the present invention provides methods for monitoring the effect of cancer treatment on the heart, and/or methods for monitoring a cancer treatment regimen. In some embodiments, the present invention provides a method for selecting subjects for a test or treatment. In some embodiments, the present invention provides a method for determining the dosage of a drug. In some embodiments, the present invention provides methods for determining the risk of a cardiovascular disease, for assessing risk of a cardiovascular disease, and/or for determining the risk of heart attack.

  本发明提供了心脏成像的新方法及其相关医疗应用。在某些实施方案中，本发明提供了一种诊断心血管疾病、状况或失调的方法。在一些实施例中，本发明提供了一种治疗或预防心血管疾病、病症或紊乱的方法。在一些实施方案中，本发明提供了监测癌症治疗对心脏影响的方法，和/或监测癌症治疗方案的方法。在一些实施方案中，本发明提供了一种选择受试者进行测试或治疗的方法。在一些实施方案中，本发明提供了一种确定药物剂量的方法。在一些实施方案中，本发明提供了确定心血管疾病风险、评估心血管疾病风险和/或确定心脏病发作风险的方法。
• Hsp9O-targeted inflammation and infection imaging and therapy
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：US10617772B2

  公开（公告）日：2020-04-14

  The present invention provides new methods for inflammation and infection imaging and related medical applications thereof. In some embodiments, the present invention provides a method for the diagnosis of inflammation and/or infection. In some embodiments, the present invention provides a method for the treatment or prevention of inflammation and/or infection. In some embodiments, the present invention provides methods for monitoring the effect of inflammation and/or infection treatment, and/or methods for monitoring an inflammation and/or infection treatment regimen. In some embodiments, the present invention provides a method for selecting subjects for an inflammation and/or infection treatment. In some embodiments, the present invention provides a method for determining the dosage of a drug for the treatment of inflammation and/or infection.

  本发明提供了炎症和感染成像的新方法及其相关医疗应用。在一些实施方案中，本发明提供了一种诊断炎症和/或感染的方法。在一些实施方案中，本发明提供了一种治疗或预防炎症和/或感染的方法。在一些实施方案中，本发明提供了监测炎症和/或感染治疗效果的方法，和/或监测炎症和/或感染治疗方案的方法。在一些实施方案中，本发明提供了一种选择受试者进行炎症和/或感染治疗的方法。在一些实施方案中，本发明提供了一种用于确定治疗炎症和/或感染的药物剂量的方法。
• HSP90-targeted inflammation and infection imaging and therapy
  申请人：Memorial Sloan Kettering Cancer Center

  公开号：US11065350B2

  公开（公告）日：2021-07-20

  The present invention provides new methods for inflammation and infection imaging and related medical applications thereof. In some embodiments, the present invention provides a method for the diagnosis of inflammation and/or infection. In some embodiments, the present invention provides a method for the treatment or prevention of inflammation and/or infection. In some embodiments, the present invention provides methods for monitoring the effect of inflammation and/or infection treatment, and/or methods for monitoring an inflammation and/or infection treatment regimen. In some embodiments, the present invention provides a method for selecting subjects for an inflammation and/or infection treatment. In some embodiments, the present invention provides a method for determining the dosage of a drug for the treatment of inflammation and/or infection.

  本发明提供了炎症和感染成像的新方法及其相关医疗应用。在一些实施方案中，本发明提供了一种诊断炎症和/或感染的方法。在一些实施方案中，本发明提供了一种治疗或预防炎症和/或感染的方法。在一些实施方案中，本发明提供了监测炎症和/或感染治疗效果的方法，和/或监测炎症和/或感染治疗方案的方法。在一些实施方案中，本发明提供了一种选择受试者进行炎症和/或感染治疗的方法。在一些实施方案中，本发明提供了一种用于确定治疗炎症和/或感染的药物剂量的方法。