tert-butyl N-[(1R)-1-[4-(hydroxymethyl)phenyl]ethyl]carbamate | 1021491-26-8

• 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: tert-butyl N-[(1R)-1-[4-(hydroxymethyl)phenyl]ethyl]carbamate
• 英文别名: tert-butyl {(1R)-1-[4-(hydroxymethyl)phenyl]ethyl}carbamate；(R)-tert-butyl 1-(4-(hydroxymethyl)phenyl)ethylcarbamate
• CAS: 1021491-26-8
• 化学式: C₁₄H₂₁NO₃
• 分子量: 251.326
• InChiKey: IKDSQAZPZFBIIK-SNVBAGLBSA-N

物化性质

• 沸点：
  401.6±33.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(1R)-1-[4-(hydroxymethyl)phenyl]ethyl]carbamate 在 manganese(IV) oxide 、 N-氯代丁二酰亚胺 、 羟胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-[3-[4-[(1R)-1-aminoethyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine trifluoroacetate
  参考文献：
  名称：

  Rational Design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): Optimization of Intra- and Intermolecular Polar Interactions of a New Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase Inhibitor

  摘要：

  The DNA damage response (DDR) is a DNA damage surveillance and repair mechanism that can limit the effectiveness of radiotherapy and DNA-damaging chemotherapy, commonly used treatment modalities in cancer. Two related kinases, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related kinase (ATR), work together as apical proteins in the DDR to maintain genome stability and cell survival in the face of potentially lethal forms of DNA damage. However, compromised ATM signaling is a common characteristic of tumor cells, which places greater reliance on ATR to mediate the DDR. In such circumstances, ATR inhibition has been shown to enhance the toxicity of DNA damaging chemotherapy to many cancer cells in multiple preclinical studies, while healthy tissue with functional ATM can tolerate ATR inhibition. ATR therefore represents a very attractive anticancer target. Herein we describe the discovery of VX-970/M6620, the first ATR inhibitor to enter clinical studies, which is based on a 2-aminopyrazine core first reported by Charrier et al. (J. Med. Chem. 2011, 54, 2320-2330, DOI: ).

  DOI：

  10.1021/acs.jmedchem.9b00426
• 作为产物：
  描述：

  methyl (R)-4-(1-((tert-butoxycarbonyl)amino)ethyl)benzoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以100%的产率得到tert-butyl N-[(1R)-1-[4-(hydroxymethyl)phenyl]ethyl]carbamate
  参考文献：
  名称：

  SUBSTITUTED PHENYLMETHYL BICYCLOCARBOXYAMIDE COMPOUNDS

  摘要：

  这项发明提供了一种化合物，其化学式为（I）。这些化合物对于治疗由VR1受体过度激活引起的疾病症状，如哺乳动物中的疼痛等，具有益处。该发明还提供了一种包含上述化合物的药物组合物。

  公开号：

  US20100087480A1

文献信息

• [EN] SULFONYLATED TETRAHYDROAZOLOPYRAZINES AND THEIR USE AS MEDICINAL PRODUCTS<br/>[FR] TÉTRAHYDROAZOLOPYRAZINES SULFONYLÉES ET LEUR UTILISATION EN TANT QUE PRODUITS MÉDICAMENTEUX
  申请人：GRUENENTHAL GMBH

  公开号：WO2010099938A1

  公开（公告）日：2010-09-10

  The present invention relates to sulfonylated tetrahydroazolopyrazines, methods for the preparation thereof, medicinal products containing these compounds and the use of substituted indole compounds for the preparation of medicinal products (Formula I).

  本发明涉及磺酰化四氢咯啉吡嗪，其制备方法，含有这些化合物的药物产品以及用于制备药物产品的取代吲哚化合物的使用（式I）。
• Sulfonylated 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine compounds and their use as pharmaceuticals
  申请人：Gruenenthal GmbH

  公开号：US08158628B2

  公开（公告）日：2012-04-17

  Sulfonylated tetrahydroazolopyrazine compounds corresponding to the formula I wherein R1, R2a, R2b, R3a, R3b, R4, R8, R9a, R9b, R10, R11, A, B, W1, W2 and W3 have the meanings defined herein, pharmaceutical compositions containing such compounds, a method for the preparation of such compounds, and the use of such compounds for treating or inhibiting various types of pain and/or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).

  化合物公式I对应的磺酰基四氢咪唑并吡嗪化合物，其中R1、R2a、R2b、R3a、R3b、R4、R8、R9a、R9b、R10、R11、A、B、W1、W2和W3的含义在此定义，包含这种化合物的药物组合物，制备这种化合物的方法，以及利用这种化合物治疗或抑制至少部分由激肽酶1受体（B1R）介导的各种类型的疼痛和/或其他情况的用途。
• Sulfonylated Tetrahydroazolopyrazines and their Use as Pharmaceuticals
  申请人：MERLA Beatrix

  公开号：US20100234387A1

  公开（公告）日：2010-09-16

  Sulfonylated tetrahydroazolopyrazine compounds corresponding to the formula I wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , R 8 , R 9a , R 9b , R 10 , R 11 , A, B, W 1 , W 2 and W 3 have the meanings defined herein, pharmaceutical compositions containing such compounds, a method for the preparation of such compounds, and the use of such compounds for treating or inhibiting various types of pain and/or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).

  公式I对应的是磺酰化四氢咪唑吡嗪化合物，其中R1、R2a、R2b、R3a、R3b、R4、R8、R9a、R9b、R10、R11、A、B、W1、W2和W3的含义如下所定义，该类化合物的制备方法、含有该类化合物的药物组合物以及利用该类化合物治疗或抑制至少部分由激肽1受体（B1R）介导的各种疼痛和/或其他疾病的用途。
• IDO-TDO dual inhibitor and related methods of use
  申请人：CMG PHARMACEUTICAL CO., LTD.

  公开号：US11370758B2

  公开（公告）日：2022-06-28

  Provided is an inhibitor of an indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) of formula (I) or a pharmaceutically acceptable salt thereof: in which W1, W2, W3, and W4, X, Y, Z1, Z2, and R1-7 are described herein. Further provided is a method of treating or preventing a IDO and/or TDO-mediated disease using an effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof.

  本发明提供了一种式（I）的吲哚胺 2，3-二氧化酶（IDO）和/或色氨酸 2，3-二氧化酶（TDO）抑制剂或其药学上可接受的盐： 其中 W1、W2、W3 和 W4、X、Y、Z1、Z2 和 R1-7 已在本文中描述。进一步提供了一种使用有效量的式（I）化合物或其药学上可接受的盐治疗或预防 IDO 和/或 TDO 介导的疾病的方法。
• SULFONYLATED TETRAHYDROAZOLOPYRAZINES AND THEIR USE AS MEDICINAL PRODUCTS
  申请人：Grünenthal GmbH

  公开号：EP2403854A1

  公开（公告）日：2012-01-11