(R)-tert-butyl 1-(3-benzyloxy)-2-hydroxypropyl-1H-1,2,3-triazole-4-carboxylate | 1853165-94-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-tert-butyl 1-(3-benzyloxy)-2-hydroxypropyl-1H-1,2,3-triazole-4-carboxylate
• 英文别名: (R)-tert-butyl 1-(3-(benzyloxy)-2-hydroxypropyl)-1H-1,2,3-triazole-4-carboxylate；tert-butyl 1-[(2R)-2-hydroxy-3-phenylmethoxypropyl]triazole-4-carboxylate
• CAS: 1853165-94-2
• 化学式: C₁₇H₂₃N₃O₄
• 分子量: 333.387
• InChiKey: YUYNKVYTMHOXPV-CQSZACIVSA-N

物化性质

• 沸点：
  502.2±60.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 1-(3-benzyloxy)-2-hydroxypropyl-1H-1,2,3-triazole-4-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 二乙胺基三氟化硫 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 、 sodium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 104.5h， 生成 (R)-1-(2-fluoro-4-(6-(2-(4-(trifluoromethyl)pyridin-2-yl)acetamido)pyridazin-3-yl)butyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide
  参考文献：
  名称：

  Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

  摘要：

  Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

  DOI：

  10.1021/acs.jmedchem.0c01398
• 作为产物：
  描述：

  (R)-苄氧甲基环氧乙烷 在 copper(l) iodide 、 sodium azide 、 氯化铵 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 (R)-tert-butyl 1-(3-benzyloxy)-2-hydroxypropyl-1H-1,2,3-triazole-4-carboxylate
  参考文献：
  名称：

  Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

  摘要：

  Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

  DOI：

  10.1021/acs.jmedchem.0c01398

文献信息

• GLS1 INHIBITORS FOR TREATING DISEASE
  申请人：Board of Regents, The University of Texas System

  公开号：US20160009704A1

  公开（公告）日：2016-01-14

  Disclosed herein are compounds and compositions useful in the treatment of GLS1 mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibition GLS1 activity in a human or animal subject are also provided.

  本文揭示了一些化合物和组合物，其结构公式为I，可用于治疗GLS1介导的疾病，如癌症。还提供了抑制人类或动物主体中GLS1活性的方法。
• HETEROCYCLIC GLS1 INHIBITORS
  申请人：Board of Regents, The University of Texas System

  公开号：EP3677579A1

  公开（公告）日：2020-07-08

  Disclosed herein are compounds and compositions useful in the treatment of GLS I mediated diseases, such as cancer, having the structure of Formula I. Methods of inhibition GLS I activity in a human or animal subject are also provided.

  本文公开了用于治疗 GLS I 介导的疾病（如癌症）的具有式 I 结构的化合物和组合物。还提供了抑制人或动物体内 GLS I 活性的方法。
• Salt forms and polymorphs of (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyrdin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide
  申请人：Board of Regents, The University of Texas System

  公开号：US10150753B2

  公开（公告）日：2018-12-11

  Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido)pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

  本文公开了化合物(R)-1-(4-(6-(2-(4-(3,3-二氟环丁氧基)-6-甲基吡啶-2-基)乙酰氨基)哒嗪-3-基)-2-氟丁基)-N-甲基-1H-1,2,3-三唑-4-甲酰胺及其盐形式和多晶型，口服后显示出更好的暴露。还提供了抑制人或动物体内 GLS1 活性的方法。
• GLS1 inhibitors for treating disease
  申请人：Board of Regents, The University of Texas System

  公开号：US10344025B2

  公开（公告）日：2019-07-09

  Disclosed herein are compounds and compositions useful in the treatment of GLS1 mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibition GLS1 activity in a human or animal subject are also provided.

  本文公开了用于治疗 GLS1 介导的疾病（如癌症）的化合物和组合物，其结构如式 I 所示： 还提供了抑制人或动物体内 GLS1 活性的方法。
• Salt forms and polymorphs of (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido)pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide
  申请人：Board of Regents, The University of Texas System

  公开号：US10899740B2

  公开（公告）日：2021-01-26

  Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido)pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

  本文公开了化合物(R)-1-(4-(6-(2-(4-(3,3-二氟环丁氧基)-6-甲基吡啶-2-基)乙酰氨基)哒嗪-3-基)-2-氟丁基)-N-甲基-1H-1,2,3-三唑-4-甲酰胺及其盐形式和多晶型，口服后显示出更好的暴露。 还提供了抑制人或动物体内 GLS1 活性的方法。