3-(叔丁氧基羰基)-2,2-二甲基丙酸甲酯 | 195387-08-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-(叔丁氧基羰基)-2,2-二甲基丙酸甲酯
• 英文名称: methyl 3-((tert-butoxycarbonyl)amino)-2,2-dimethylpropanoate
• 英文别名: Methyl 3-((tert-butoxycarbonyl)amino)-2,2-dimethylpropanoate；methyl 2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 195387-08-7
• 化学式: C₁₁H₂₁NO₄
• 分子量: 231.292
• InChiKey: FUDZEIOVTBDUSB-UHFFFAOYSA-N

物化性质

• 沸点：
  313.4±25.0 °C(Predicted)
• 密度：
  1.023±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2924199090

反应信息

• 作为反应物：
  描述：

  3-(叔丁氧基羰基)-2,2-二甲基丙酸甲酯 在 吗啉 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 三甲基氯硅烷 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙腈 为溶剂， 反应 96.5h， 生成 cryptophycin 52
  参考文献：
  名称：

  Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies

  摘要：

  Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58-1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI-N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112364
• 作为产物：
  描述：

  3-((叔丁氧基羰基)氨基)-2,2-二甲基丙酸 、 三甲基硅烷化重氮甲烷 以 甲醇 、 二氯甲烷 为溶剂， 以100%的产率得到3-(叔丁氧基羰基)-2,2-二甲基丙酸甲酯
  参考文献：
  名称：

  [EN] NOVEL CRYPTOPHYCIN COMPOUNDS AND CONJUGATES, THEIR PREPARATION AND THEIR THERAPEUTIC USE
  [FR] NOUVEAUX COMPOSÉS ET CONJUGUÉS DE CRYPTOPHYCINE, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE

  摘要：

  本发明涉及公式（I）的隐藻素化合物。该发明还涉及隐藻素有效载荷、隐藻素偶联物、含有它们的组合物及其治疗用途，尤其是作为抗癌剂。该发明还涉及制备这些偶联物的过程。

  公开号：

  WO2017076998A1

文献信息

• [EN] 4 -HYDROXY- ISOQUINOLINE COMPOUNDS AS HIF HYDROXYLASE INHIBITORS<br/>[FR] COMPOSÉS 4-HYDROXY-ISOQUINOLÉINE COMME INHIBITEURS D'HYDROXYLASE HIF
  申请人：FIBROGEN INC

  公开号：WO2013134660A1

  公开（公告）日：2013-09-12

  The present invention relates to novel compounds of formula (I), and compositions capable of inhibiting PHD1 enzyme activity selectively over other isoforms, for example, PHD2 and/or PHD3 enzymes. The invention also relates to compounds of formula (I) for use in disorders such as muscle degeneration, colitis, IBD, and certain ischemias.

  本发明涉及式(I)的新化合物，以及能够选择性地抑制PHD1酶活性而不影响其他同工酶（例如PHD2和/或PHD3酶）的组合物。该发明还涉及式(I)的化合物在肌肉退化、结肠炎、炎症性肠病和某些缺血症等疾病中的应用。
• THERAPEUTIC PEPTIDES
  申请人：Strom Morten

  公开号：US20130035296A1

  公开（公告）日：2013-02-07

  The present invention provides a peptide, peptidomimetic or amino acid derivative having a net positive charge of at least +2 and incorporating a disubstituted β amino acid, each of the substituting groups in the β amino acid, which may be the same or different, comprises at least (7) non-hydrogen atoms, is lipophilic and has at least one cyclic group, one or more cyclic groups within a substituting group may be linked or fused to one or more cyclic groups within the other substituting group and where cyclic groups are fused in this way the combined total number of non-hydrogen atoms for the two substituting groups is at least (12), for use as a cytolytic therapeutic agent; as well as non therapeutic uses of these molecules and certain defined novel compounds from within this definition.

  本发明提供了一种具有至少+2的净正电荷并且包含二取代β氨基酸的肽、肽类似物或氨基酸衍生物，β氨基酸中的每个取代基（可能相同也可能不同）包括至少（7）个非氢原子，具有亲脂性并且至少有一个环状基团，一个或多个取代基内的环状基团可以连接或融合到另一个取代基内的一个或多个环状基团中，当环状基团以这种方式融合时，两个取代基的非氢原子的总数至少为（12），用作溶细胞治疗剂；以及这些分子的非治疗用途以及从该定义中确定的某些新化合物。
• 4 -HYDROXY- ISOQUINOLINE COMPOUNDS AS HIF HYDROXYLASE INHIBITORS
  申请人：FIBROGEN, INC.

  公开号：US20150038528A1

  公开（公告）日：2015-02-05

  The present invention relates to novel compounds of formula (I), and compositions capable of inhibiting PHD1 enzyme activity selectively over other isoforms, for example, PHD2 and/or PHD3 enzymes. The invention also relates to compounds of formula (I) for use in disorders such as muscle degeneration, colitis, IBD, and certain ischemias.

  本发明涉及公式（I）的新型化合物及其组合物，能够选择性地抑制PHD1酶活性，而不影响其他同工酶，例如PHD2和/或PHD3酶。本发明还涉及公式（I）的化合物在肌肉退化、结肠炎、炎症性肠病和某些缺血症等疾病中的使用。
• 4-hydroxy-isoquinoline compounds as HIF hydroxylase inhibitors
  申请人：FIBROGEN, INC.

  公开号：US09409892B2

  公开（公告）日：2016-08-09

  The present invention relates to novel compounds of formula (I), and compositions capable of inhibiting PHD1 enzyme activity selectively over other isoforms, for example, PHD2 and/or PHD3 enzymes. The invention also relates to compounds of formula (I) for use in disorders such as muscle degeneration, colitis, IBD, and certain ischemias.

  本发明涉及公式（I）的新化合物和能够选择性地抑制PHD1酶活性的组合物，例如，PHD2和/或PHD3酶。本发明还涉及公式（I）的化合物，用于治疗肌肉退化、结肠炎、炎症性肠病和某些缺血症。
• Cryptophycin compounds and conjugates, their preparation and their therapeutic use
  申请人：SANOFI

  公开号：US10941139B2

  公开（公告）日：2021-03-09

  The present invention relates to cryptophycin compounds of formula (I). The invention also relates to cryptophycin payloads, to cryptophycin conjugates, to compositions containing them and to their therapeutic use, especially as anticancer agents. The invention also relates to the process for preparing these conjugates.

  本发明涉及式（I）的隐球霉素化合物。本发明还涉及隐球菌苷有效载荷、隐球菌苷共轭物、含有它们的组合物及其治疗用途，特别是作为抗癌剂。本发明还涉及制备这些共轭物的工艺。