2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde | 1446321-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
• 英文别名: 2-Fluoro-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde；2-fluoro-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde
• CAS: 1446321-56-7
• 化学式: C₁₉H₁₈FN₃O₂
• 分子量: 339.369
• InChiKey: GTAYSDREQLXNMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氟水杨醛 、 3-氯甲基-2-(1-异丙基-1H-吡唑-5-基)吡啶盐酸盐 在 potassium carbonate 作用下， 以99%的产率得到2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
  参考文献：
  名称：

  Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin

  摘要：

  We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of similar to 150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 (36) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).

  DOI：

  10.1021/acsmedchemlett.6b00491

文献信息

• [EN] SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION<br/>[FR] COMPOSÉS BENZALDÉHYDE SUBSTITUÉS ET PROCÉDÉS D'UTILISATION DE CEUX-CI DANS L'AUGMENTATION DE L'OXYGÉNATION DES TISSUS
  申请人：GLOBAL BLOOD THERAPEUTICS INC

  公开号：WO2013102142A1

  公开（公告）日：2013-07-04

  Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.

  提供了替代苯甲醛及其衍生物，其作为血红蛋白的变构调节剂，以及其制备的方法和中间体，包括这些调节剂的药物组合物，以及在治疗由血红蛋白介导的疾病和需要增加组织氧合的疾病中使用它们的方法。
• [EN] COMPOSITIONS FOR USE IN METHODS OF TREATMENT OF HEMOGLOBIN DISORDERS<br/>[FR] COMPOSITIONS DESTINÉES À ÊTRE UTILISÉES DANS DES MÉTHODES DE TRAITEMENT DES HÉMOGLOBINOPATHIES
  申请人：AKEBIA THERAPEUTICS INC

  公开号：WO2019028150A1

  公开（公告）日：2019-02-07

  The present disclosure relates to hypoxia inducible factor (HIF) prolyl hydroxylase inhibitor compounds and pharmaceutically acceptable salts thereof, to compositions comprising the HIF prolyl hydroxylase inhibitor compounds (e.g., Compound 1), and to methods for treating or preventing hemoglobin disorders such as sickle cell diseases, including sickle cell anemia, hemoglobin SC disease, and sickle β thalassemia, and β thalassemias, including βo-(major) thalassemia and β+-(minor) thalassemia. In addition, the present disclosure relates to specific doses of HIF prolyl hydroxylase inhibitor in treating or preventing hemoglobin disorders such as sickle cell diseases, including sickle cell anemia, hemoglobin SC disease, and sickle β thalassemia, and β thalassemias, including βo-(major) thalassemia and β+-(minor) thalassemia.

  本公开涉及缺氧诱导因子（HIF）脯氨酸羟化酶抑制剂化合物及其药用盐，包括含有HIF脯氨酸羟化酶抑制剂化合物（例如，化合物1）的组合物，以及用于治疗或预防血红蛋白疾病如镰状细胞病，包括镰状细胞贫血、血红蛋白SC病和镰状β地中海贫血，以及β地中海贫血，包括βo-（重型）地中海贫血和β+（轻型）地中海贫血的方法。此外，本公开涉及在治疗或预防血红蛋白疾病如镰状细胞病，包括镰状细胞贫血、血红蛋白SC病和镰状β地中海贫血，以及β地中海贫血，包括βo-（重型）地中海贫血和β+（轻型）地中海贫血中的特定剂量的HIF脯氨酸羟化酶抑制剂。
• COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20170174654A1

  公开（公告）日：2017-06-22

  Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

  本文提供的是适用于调节血红蛋白的化合物和药物组合物，它们的制备方法和中间体，以及在治疗由血红蛋白介导的疾病和需要组织和/或细胞氧合的疾病中使用它们的方法。
• SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20130190315A1

  公开（公告）日：2013-07-25

  Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.

  提供一种替代苯甲醛及其衍生物，其作为血红蛋白的异构调节剂，以及其制备的方法和中间体，包括该调节剂的制药组合物，以及使用该组合物治疗由血红蛋白介导的疾病和需要增加组织氧合的疾病的方法。
• INTERMEDIATES TO OBTAIN SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION
  申请人：Global Blood Therapeutics, Inc.

  公开号：EP3738434A1

  公开（公告）日：2020-11-18

  Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.

  本文提供了可作为血红蛋白异位调节剂的取代苯甲醛及其衍生物、制备它们的方法和中间体、包含这些调节剂的药物组合物，以及将它们用于治疗由血红蛋白介导的疾病和可从增加组织含氧量中获益的疾病的方法。