diethyl 2,2-difluoro-4-methylenepentanedioate | 1307857-46-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: diethyl 2,2-difluoro-4-methylenepentanedioate
• 英文别名: 1,5-diethyl 2,2-difluoro-4-methylenepentanedioate；Diethyl 2,2-difluoro-4-methylenepentanedioate；diethyl 2,2-difluoro-4-methylidenepentanedioate
• CAS: 1307857-46-0
• 化学式: C₁₀H₁₄F₂O₄
• 分子量: 236.216
• InChiKey: CEBFZCRCMYROJV-UHFFFAOYSA-N

物化性质

• 沸点：
  232.8±40.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2917190090

反应信息

• 作为反应物：
  描述：

  diethyl 2,2-difluoro-4-methylenepentanedioate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以75%的产率得到2,2-difluoro-4-methylenepentanedioic acid
  参考文献：
  名称：

  2-Difluoromethylene-4-methylenepentanoic Acid, A Paradoxical Probe Able To Mimic the Signaling Role of 2-Oxoglutaric Acid in Cyanobacteria

  摘要：

  2-Difluoromethylene-4-methylenepentanoic acid (DFMPA), a seemingly deviated analog of 2-oxoglutaric acid (2-OG), could surprisingly mimic its signaling function in cyanobacteria. Computer modeling revealed the favorable binding of DFMPA toward the 2-OG receptor, NtcA, via mutual conformational changes, suggesting that structural alteration of 2-OG is tolerated for it to exercise its signaling role. This extremely useful finding could be exploited for the design of affinity probes with which to study new 2-OG receptors In related signaling pathways.

  DOI：

  10.1021/ol2009544
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 2-溴甲基丙烯酸乙酯 在 copper(l) cyanide 、 锌 作用下， 以 四氢呋喃 为溶剂， 生成 diethyl 2,2-difluoro-4-methylenepentanedioate
  参考文献：
  名称：

  SAR 对 TET2 催化域抑制的见解：2-Hydroxy-4-Methylene-pentanedicarboxylates 的合成

  摘要：

  由 3 个成员 TET1-3 组成的 TET（十一十​​一易位）双加氧酶家族在 DNA 去甲基化中起关键作用。这些过程调节决定细胞谱系、存活、增殖和分化的转录程序。我们在此描述的研究的动力来自于开发具有细胞活性和特异性的 TET 酶的启发性小分子探针的需要。这些研究是在 TET2 在造血系统中的重要性和骨髓疾病中功能丧失体细胞 TET2 突变的优势的背景下进行的。我们已经确定 2-羟基-4-亚甲基-戊二甲酸2a与 TET2 催化结构域中的共底物 α-KG 可逆竞争，并以 IC 50抑制双加氧酶活性 在无细胞系统中，在 10 μM α-KG 时 = 11.0 ± 0.9 μM，在 TET2 催化结构域中结合，K d  = 0.3 ± 0.12 μM。

  DOI：

  10.1016/j.bmc.2021.116141

文献信息

• ANTITUMOR TET2 MODULATING COMPOUNDS
  申请人：THE CLEVELAND CLINIC FOUNDATION

  公开号：US20200306221A1

  公开（公告）日：2020-10-01

  A method of treating cancer is described. The method includes administering a therapeutically effective amount of a TET2 activating compound or pharmaceutically acceptable salt thereof to a subject in need of treatment. The TET2 activating compounds are a-ketoglutarate derivatives. A method of treating or preventing cancer in a subject that includes the step of analyzing a biological sample to determine if cells of the biological sample exhibit a TET2 mutation in addition to administering a TET2 activator is also described.
• SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates
  作者：Anand D. Tiwari、Yihong Guan、Dale R. Grabowski、Jaroslaw P. Maciejewski、Babal K. Jha、James G. Phillips

  DOI：10.1016/j.bmc.2021.116141

  日期：2021.6

  The TET (Ten-Eleven Translocation) dioxygenase enzyme family comprising 3 members, TET1-3, play key roles in DNA demethylation. These processes regulate transcription programs that determine cell lineage, survival, proliferation, and differentiation. The impetus for our investigations described here is derived from the need to develop illuminating small molecule probes for TET enzymes with cellular

  由 3 个成员 TET1-3 组成的 TET（十一十​​一易位）双加氧酶家族在 DNA 去甲基化中起关键作用。这些过程调节决定细胞谱系、存活、增殖和分化的转录程序。我们在此描述的研究的动力来自于开发具有细胞活性和特异性的 TET 酶的启发性小分子探针的需要。这些研究是在 TET2 在造血系统中的重要性和骨髓疾病中功能丧失体细胞 TET2 突变的优势的背景下进行的。我们已经确定 2-羟基-4-亚甲基-戊二甲酸2a与 TET2 催化结构域中的共底物 α-KG 可逆竞争，并以 IC 50抑制双加氧酶活性 在无细胞系统中，在 10 μM α-KG 时 = 11.0 ± 0.9 μM，在 TET2 催化结构域中结合，K d  = 0.3 ± 0.12 μM。
• 2-Difluoromethylene-4-methylenepentanoic Acid, A Paradoxical Probe Able To Mimic the Signaling Role of 2-Oxoglutaric Acid in Cyanobacteria
  作者：Xinjun Liu、Han Chen、Erik Laurini、Yang Wang、Valentina Dal Col、Paola Posocco、Fabio Ziarelli、Maurizio Fermeglia、Cheng-Cai Zhang、Sabrina Pricl、Ling Peng

  DOI：10.1021/ol2009544

  日期：2011.6.3

  2-Difluoromethylene-4-methylenepentanoic acid (DFMPA), a seemingly deviated analog of 2-oxoglutaric acid (2-OG), could surprisingly mimic its signaling function in cyanobacteria. Computer modeling revealed the favorable binding of DFMPA toward the 2-OG receptor, NtcA, via mutual conformational changes, suggesting that structural alteration of 2-OG is tolerated for it to exercise its signaling role. This extremely useful finding could be exploited for the design of affinity probes with which to study new 2-OG receptors In related signaling pathways.