2,2-二氟丙烷酰肼 | 1033077-25-6

• 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: 2,2-二氟丙烷酰肼
• 英文名称: 2,2-difluoropropanehydrazide
• CAS: 1033077-25-6
• 化学式: C₃H₆F₂N₂O
• 分子量: 124.09
• InChiKey: SRTQHDWTGJDJQM-UHFFFAOYSA-N

物化性质

• 沸点：
  233.9±35.0 °C(Predicted)
• 密度：
  1.258±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-二氟丙烷酰肼 、 (S)-tert-butyl 2-methyl-5-thioxopiperazine-1-carboxylate 以 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 以69%的产率得到(S)-tert-butyl 3-(1,1-difluoroethyl)-6-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate
  参考文献：
  名称：

  Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering

  摘要：

  The propensity for cancer cells to accumulate additional centrosomes relative to normal cells could be exploited for therapeutic benefit in oncology. Following literature reports that suggested TNKS1 (tankyrase 1) and PARP16 may be involved with spindle structure and function and may play a role in suppressing multi-polar spindle formation in cells with supernumerary centrosomes, we initiated a phenotypic screen to look for small molecule poly (ADP-ribose) polymerase (PARP) enzyme family inhibitors that could produce a multi-polar spindle phenotype via declustering of centrosomes. Screening of AstraZeneca's collection of phthalazinone PARP inhibitors in HeLa cells using high-content screening techniques identified several compounds that produced a multi-polar spindle phenotype at low nanomolar concentrations. Characterization of these compounds across a broad panel of PARP family enzyme assays indicated that they had activity against several PARP family enzymes, including PARP1, 2, 3, 5a, 5b, and 6. Further optimization of these initial hits for improved declustering potency, solubility, permeability, and oral bioavailability resulted in AZ0108, a PARP1, 2, 6 inhibitor that potently inhibits centrosome clustering and is suitable for in vivo efficacy and tolerability studies. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.079
• 作为产物：
  描述：

  2,2-二氟丙酸甲酯 在 肼 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以100%的产率得到2,2-二氟丙烷酰肼
  参考文献：
  名称：

  Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering

  摘要：

  The propensity for cancer cells to accumulate additional centrosomes relative to normal cells could be exploited for therapeutic benefit in oncology. Following literature reports that suggested TNKS1 (tankyrase 1) and PARP16 may be involved with spindle structure and function and may play a role in suppressing multi-polar spindle formation in cells with supernumerary centrosomes, we initiated a phenotypic screen to look for small molecule poly (ADP-ribose) polymerase (PARP) enzyme family inhibitors that could produce a multi-polar spindle phenotype via declustering of centrosomes. Screening of AstraZeneca's collection of phthalazinone PARP inhibitors in HeLa cells using high-content screening techniques identified several compounds that produced a multi-polar spindle phenotype at low nanomolar concentrations. Characterization of these compounds across a broad panel of PARP family enzyme assays indicated that they had activity against several PARP family enzymes, including PARP1, 2, 3, 5a, 5b, and 6. Further optimization of these initial hits for improved declustering potency, solubility, permeability, and oral bioavailability resulted in AZ0108, a PARP1, 2, 6 inhibitor that potently inhibits centrosome clustering and is suitable for in vivo efficacy and tolerability studies. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.079

文献信息

• Chemical Compound
  申请人：Faull Alan Wellington

  公开号：US20080139612A1

  公开（公告）日：2008-06-12

  The present invention relates to 4-[3-(1,1-difluoroethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-1-(1R,3R)-3-(3,5-difluorophenyl)-1-methyl-3-[1-(methylsulfonyl)piperidin-4-yl]propyl}piperidine (I): or a pharmaceutically acceptable salt thereof, as well as processes for the preparation of this compound and its use in the treatment of CCR5 disease states.

  本发明涉及4-[3-(1,1-二氟乙基)-5-甲基-4H-1,2,4-三唑-4-基]-1-(1R,3R)-3-(3,5-二氟苯基)-1-甲基-3-[1-(甲基磺酰基)哌啶-4-基]丙基}哌啶(I)或其药学上可接受的盐，以及制备该化合物的方法和在治疗CCR5疾病状态中使用该化合物的方法。
• Piperidine Derivative Used for Treating Chemokine Receptor 5 Mediated Diseases
  申请人：Faull Alan Wellington

  公开号：US20100099708A1

  公开（公告）日：2010-04-22

  The present invention relates to 4-[3-(1,1-difluoroethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-1-(1R,3R)-3-(3,5-difluorophenyl)-1-methyl-3-[1-(methylsulfonyl)ρiperidin-4-yl]propyl}piperidine formula (I): or a pharmaceutically acceptable salt thereof, as well as processes for the preparation of this compound and its use in the treatment of CCR5 disease states.

  本发明涉及4-[3-(1,1-二氟乙基)-5-甲基-4H-1,2,4-三唑-4-基]-1-(1R,3R)-3-(3,5-二氟苯基)-1-甲基-3-[1-(甲基磺酰基)哌啶-4-基]丙基}哌啶式(I)或其药学上可接受的盐，以及制备该化合物的方法和其在治疗CCR5疾病状态中的应用。