2-(4-(di-tert-butoxyphosphoryloxy)phenyl)acetic acid | 1351831-48-5

• 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: 2-(4-(di-tert-butoxyphosphoryloxy)phenyl)acetic acid
• 英文别名: 2-(4-(Di-tert-butoxyphosphoryloxy)phenyl)acetic acid；2-[4-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]phenyl]acetic acid
• CAS: 1351831-48-5
• 化学式: C₁₆H₂₅O₆P
• 分子量: 344.345
• InChiKey: GZRRVOIHUVDWFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  氯甲基氯磺酸酯 、 2-(4-(di-tert-butoxyphosphoryloxy)phenyl)acetic acid 在 四丁基硫酸氢铵 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以2.53 g的产率得到chloromethyl 2-(4-((di-tert-butoxyphosphoryl)oxy)phenyl)acetate
  参考文献：
  名称：

  Prodrug Strategies to Improve the Solubility of the HCV NS5A Inhibitor Pibrentasvir (ABT-530)

  摘要：

  A research program to discover solubilizing prodrugs of the HCV NS5A inhibitor pibrentasvir (PIB) identified phosphomethyl analog 2 and trimethyl-lock (TML) prodrug 9. The prodrug moiety is attached to a benzimidazole nitrogen atom via an oxymethyl linkage to allow for rapid and complete release of the drug for absorption following phosphate removal by intestinal alkaline phosphatase. These prodrugs have good hydrolytic stability properties and improved solubility compared to PIB, both in aqueous buffer (pH 7) and FESSIF (pH 5). TML prodrug 9 provided superior in vivo performance, delivering high plasma concentrations of PIB in PK studies conducted in mice, dogs, and monkeys. The improved dissolution properties of these phosphate prodrugs provide them the potential to simplify drug dosage forms for PIB-containing HCV therapy.

  DOI：

  10.1021/acs.jmedchem.0c00956
• 作为产物：
  描述：

  N,N-二乙基亚磷酰胺二叔丁酯 在 四氮唑 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.08h， 生成 2-(4-(di-tert-butoxyphosphoryloxy)phenyl)acetic acid
  参考文献：
  名称：

  [EN] ALKYL, FLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS
  [FR] COMPOSÉS ALKYL, FLUOROALKYL-1,4-BENZODIAZÉPINONES

  摘要：

  公开的是Formula (I)的化合物和/或其盐：其中：R1为CH2CH2CF3；R2为CH2（环丙基）、CH（CH3）（环丙基）或CH2CH2CH3；R3为H、CH3或Rx；R4为H或Ry；Rx、Ry、Ra、Rb、Rc、y和z在此定义。还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病的进展方面非常有用，如癌症。Formula (I)的化合物还包括Notch抑制剂化合物的前药。

  公开号：

  WO2014047374A1

文献信息

• [EN] HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME<br/>[FR] COMPOSÉS HÉTÉROARYLE UTILES EN TANT QU'INHIBITEURS DE L'ENZYME D'ACTIVATION SUMO
  申请人：DUFFEY MATTHEW O

  公开号：WO2016004136A1

  公开（公告）日：2016-01-07

  Disclosed are chemical entities which are compounds of formula (I); or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra', Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

  公开了公式(I)的化合物或其药物可接受的盐； 其中Y、Ra、Ra'、Rb、Rc、X1、X2、X3、Rd、Z1和Z2具有本文所述的值，并且星号位置表示的立体化学配置指示绝对立体化学。 根据本公开的化学实体可用作Sumo激活酶（SAE）的抑制剂。 进一步提供了包含本公开化合物的药物组合物以及使用该组合物治疗增殖性、炎症性、心血管和神经退行性疾病或病症的方法。
• [EN] ALKYL, FLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS<br/>[FR] COMPOSÉS ALKYL, FLUOROALKYL-1,4-BENZODIAZÉPINONES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014047374A1

  公开（公告）日：2014-03-27

  Disclosed are compounds of Formula (I) and/or salts thereof: (I) wherein: R1 is CH2CH2CF3; R2 is CH2(cyclopropyl), CH(CH3)(cyclopropyl), or CH2CH2CH3; R3 is H, CH3, or Rx; R4 is H or Ry; and Rx, Ry, Ra, Rb, Rc, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer. The compounds of Formula (I) also include prodrugs of the Notch inhibitor compounds.

  公开的是Formula (I)的化合物和/或其盐：其中：R1为CH2CH2CF3；R2为CH2（环丙基）、CH（CH3）（环丙基）或CH2CH2CH3；R3为H、CH3或Rx；R4为H或Ry；Rx、Ry、Ra、Rb、Rc、y和z在此定义。还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病的进展方面非常有用，如癌症。Formula (I)的化合物还包括Notch抑制剂化合物的前药。
• [EN] PRODRUGS OF 1,4-BENZODIAZEPINONE COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS 1,4-BENZODIAZÉPINONES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014047391A1

  公开（公告）日：2014-03-27

  Disclosed are compounds of Formula (I) and salts thereof, wherein: a) R1 is H or CH3, and R2 is Ry; or b) R1 is Rx and R2 is H; wherein Rx and Ry are disclosed herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are prodrugs of compounds that are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  揭示了Formula (I)的化合物及其盐，其中：a) R1为H或CH3，R2为Ry；或b) R1为Rx，R2为H；其中Rx和Ry在此处披露。还披露了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物是用于治疗、预防或减缓多种治疗领域的疾病或障碍的化合物的前药，如癌症。
• HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20200085821A1

  公开（公告）日：2020-03-19

  Disclosed are chemical entities which are compounds of formula (I): or pharmaceutically acceptable salts thereof; wherein Y, R a , R a ′, R b , R c , X 1 , X 2 , X 3 , R d , Z 1 , and Z 2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

  本发明揭示了化学实体，其为式（I）的化合物或其药学上可接受的盐；其中Y、Ra、Ra′、Rb、Rc、X1、X2、X3、Rd、Z1和Z2具有所述的值，星号标记的立体化学构型表示绝对立体化学。根据本发明的化学实体可用作Sumo激活酶（SAE）的抑制剂。还提供了含有本发明化合物的制药组合物以及使用该组合物治疗增殖性、炎症性、心血管和神经退行性疾病或疾患的方法。
• ALKYL, FLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150239851A1

  公开（公告）日：2015-08-27

  Disclosed are compounds of Formula (I) and/or salts thereof: (I) wherein: R 1 is CH 2 CH 2 CF 3 ; R 2 is CH 2 (cyclopropyl), CH(CH 3 )(cyclopropyl), or CH 2 CH 2 CH 3 ; R 3 is H, CH 3 , or R x ; R 4 is H or R y ; and R x , R y , R a , R b , R c , y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer. The compounds of Formula (I) also include prodrugs of the Notch inhibitor compounds.

  揭示了公式（I）的化合物和/或其盐：（I）其中：R1为CH2CH2CF3; R2为CH2（环丙基），CH（CH3）（环丙基）或CH2CH2CH3; R3为H，CH3或Rx; R4为H或Ry; Rx，Ry，Ra，Rb，Rc，y和z如本文所定义。还揭示了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗癌症等各种治疗领域中用于治疗，预防或减缓疾病或障碍的进展。公式（I）的化合物还包括Notch抑制剂化合物的前药。