1-chloro-3,5-difluoro-2-iodobenzene | 1242339-98-5

• 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: 1-chloro-3,5-difluoro-2-iodobenzene
• 英文别名: 6-Chloro-2,4-difluoroiodobenzene
• CAS: 1242339-98-5
• 化学式: C₆H₂ClF₂I
• 分子量: 274.436
• InChiKey: FCGGRCAGASFINA-UHFFFAOYSA-N

物化性质

• 沸点：
  211.8±35.0 °C(Predicted)
• 密度：
  2.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-chloro-3,5-difluoro-2-iodobenzene 在 四(三苯基膦)钯 、 水 、 sodium carbonate 、 bis(pyridine)iodonium tetrafluoroborate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 Methyl 3-[[5-(2-chloro-4,6-difluorophenyl)-2-hydroxy-3-iodobenzoyl]amino]propanoate
  参考文献：
  名称：

  Optimization of kinetic stabilizers of tetrameric transthyretin: A prospective ligand efficiency-guided approach

  摘要：

  In the past few years, attempts have been made to use decision criteria beyond Lipinski's guidelines (Rule of five) to guide drug discovery projects more effectively. Several variables and formulations have been proposed and investigated within the framework of multiparameter optimization methods to guide drug discovery. In this context, the combination of Ligand Efficiency Indices (LEI) has been predominantly used to map and monitor the drug discovery process in a retrospective fashion. Here we provide an example of the use of a novel application of the LEI methodology for prospective lead optimization by using the transthyretin (TTR) fibrillogenesis inhibitor iododiflunisal (IDIF) as example. Using this approach, a number of compounds with theoretical efficiencies higher than the reference compound IDIF were identified. From this group, ten compounds were selected, synthesized and biologically tested. Half of the compounds (5, 6, 7, 8 and 10) showed potencies in terms of IC50 inhibition of TTR aggregation equal or higher than the lead compound. These optimized compounds mapped within the region of more efficient candidates in the corresponding experimental nBEI-NSEI plot, matching their position in the theoretical optimization plane that was used for the prediction. Due to their upstream (North-Eastern) position in the progression lines of NPOL = 3 or 4 of the nBEI-NSEI plot, three of them (5, 6 and 8) are more interesting candidates than iododiflunisal because they have been optimized in the three crucial LEI variables of potency, size and polarity at the same time. This is the first example of the effectiveness of using the combined LEIs within the decision process to validate the application of the LEI formulation for the prospective optimization of lead compounds.

  DOI：

  10.1016/j.bmc.2020.115794
• 作为产物：
  描述：

  6-氯-2,4-二氟苯胺 在 copper(l) iodide 、 亚硝酸特丁酯 、 四丁基碘化铵 作用下， 以 乙腈 为溶剂， 生成 1-chloro-3,5-difluoro-2-iodobenzene
  参考文献：
  名称：

  Optimization of kinetic stabilizers of tetrameric transthyretin: A prospective ligand efficiency-guided approach

  摘要：

  In the past few years, attempts have been made to use decision criteria beyond Lipinski's guidelines (Rule of five) to guide drug discovery projects more effectively. Several variables and formulations have been proposed and investigated within the framework of multiparameter optimization methods to guide drug discovery. In this context, the combination of Ligand Efficiency Indices (LEI) has been predominantly used to map and monitor the drug discovery process in a retrospective fashion. Here we provide an example of the use of a novel application of the LEI methodology for prospective lead optimization by using the transthyretin (TTR) fibrillogenesis inhibitor iododiflunisal (IDIF) as example. Using this approach, a number of compounds with theoretical efficiencies higher than the reference compound IDIF were identified. From this group, ten compounds were selected, synthesized and biologically tested. Half of the compounds (5, 6, 7, 8 and 10) showed potencies in terms of IC50 inhibition of TTR aggregation equal or higher than the lead compound. These optimized compounds mapped within the region of more efficient candidates in the corresponding experimental nBEI-NSEI plot, matching their position in the theoretical optimization plane that was used for the prediction. Due to their upstream (North-Eastern) position in the progression lines of NPOL = 3 or 4 of the nBEI-NSEI plot, three of them (5, 6 and 8) are more interesting candidates than iododiflunisal because they have been optimized in the three crucial LEI variables of potency, size and polarity at the same time. This is the first example of the effectiveness of using the combined LEIs within the decision process to validate the application of the LEI formulation for the prospective optimization of lead compounds.

  DOI：

  10.1016/j.bmc.2020.115794

文献信息

• PYRIDINO[1,2-A]PYRIMIDONE ANALOGUE USED AS PI3K INHIBITOR
  申请人：Chia Tai Tianqing Pharmaceutical Group Co.,Ltd

  公开号：EP3159341A1

  公开（公告）日：2017-04-26

  Disclosed is a pyridino[1,2-a]pyrimidone analogue used as a PI3K inhibitor. The present invention particularly relates to a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

  本发明公开了一种用作 PI3K 抑制剂的吡啶并[1,2-a]嘧啶酮类似物。本发明尤其涉及一种由式（I）代表的化合物或其药学上可接受的盐。
• [EN] PROCESS OF MANUFACTURING POLYOLS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE POLYOLS
  申请人：DOW GLOBAL TECHNOLOGIES LLC

  公开号：WO2019055727A1

  公开（公告）日：2019-03-21

  A method of producing a polyether polyol includes reacting a low molecular weight initiator with one or more monomers in the presence of a polymerization catalyst, and the low molecular weight initiator has a nominal hydroxyl functionality of at least 2. The one or more monomers includes at least one selected from propylene oxide and butylene oxide. The polymerization catalyst is a Lewis acid catalyst having the general formula M(R1)1(R2)1(R3)1(R4)0 or 1, whereas M is boron, aluminum, indium, bismuth or erbium, R1, R2, R3, and R4 are each independent, R1 includes a fluoroalkyl-substituted phenyl group, R2 incudes a fluoroalkyl-substituted phenyl group or a fluoro/chloro-substituted phenyl group, R3 includes a fluoroalkyl-substituted phenyl group or a fluoro/chloro-substituted phenyl group, and optional R4 includes a functional group or functional polymer group, R1 being different from at least one of R2 and R3.
• [EN] PROCESS OF MANUFACTURING POLYOLS<br/>[FR] PROCÉDÉ DE FABRICATION DE POLYOLS
  申请人：DOW GLOBAL TECHNOLOGIES LLC

  公开号：WO2019055734A1

  公开（公告）日：2019-03-21

  A method of producing a polyether polyol includes reacting a low molecular weight initiator with ethylene oxide in the presence of a polymerization catalyst, and the low molecular weight initiator has a nominal hydroxyl functionality at least 2. The polymerization catalyst is a Lewis acid catalyst having the general formula M(R1)1(R2)1(R3)1(R4)0 or 1, whereas M is boron, aluminum, indium, bismuth or erbium, R1, R2, R3, and R4 are each independent, R1 includes a fluoroalkyl-substituted phenyl group, R2 incudes a fluoroalkyl-substituted phenyl group or a fluoro/chloro-substituted phenyl group, R3 includes a fluoroalkyl-substituted phenyl group or a fluoro/chloro-substituted phenyl group, and optional R4 includes a functional group or functional polymer group, R1 being different from at least one of R2 and R3.
• [EN] PROCESS OF MANUFACTURING SURFACTANTS AND LUBRICANTS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE TENSIOACTIFS ET DE LUBRIFIANTS
  申请人：DOW GLOBAL TECHNOLOGIES LLC

  公开号：WO2019055742A1

  公开（公告）日：2019-03-21

  A method of producing an alcohol ethoxylate surfactant or lubricant, the method including reacting a low molecular weight initiator with ethylene oxide in the presence of a polymerization catalyst, the low molecular weight initiator having a nominal hydroxyl functionality at least 1, and the polymerization catalyst being a Lewis acid catalyst having the general formula M(R1)I(R2)I(R3)I(R4)0 or 1, whereas M is boron, aluminum, indium, bismuth or erbium, R1, R2, R3, and R4 are each independent, R1 includes a first fluoroalkyl-substituted phenyl group, R2 includes a second fluoroalkyl-substituted phenyl group or a first fluoro/chloro- substituted phenyl group, R3 includes a third fluoroalkyl-substituted phenyl group or a second fluoro/chloro-substituted phenyl group, and optional R4 includes a functional group or functional polymer group, R1 being different from at least one of R2 and R3. The method further including forming an alcohol ethoxylate surfactant or lubricant having a number average molecular weight of greater than the number average molecular weight of the low molecular weight initiator in the presence of the Lewis acid catalyst.
• [EN] POLYURETHANES AND METHOD FOR MAKING POLYURETHANES<br/>[FR] POLYURÉTHANES ET PROCÉDÉ DE FABRICATION DE POLYURÉTHANES
  申请人：DOW GLOBAL TECHNOLOGIES LLC

  公开号：WO2020068493A1

  公开（公告）日：2020-04-02

  Polyurethanes are made in a one-shot process from one or more polyols having a hydroxyl equivalent weight of at least 350, wherein at least 50% of the weight of iii) is a hydroxyl-containing polymer of propylene oxide, the hydroxyl-containing polymer of propylene oxide having a hydroxyl equivalent weight of at least 350, an average of 1.8 to 3 hydroxyl groups per molecule of which hydroxyl groups 40 to 70% are primary hydroxyl groups, an oxyethylene content of no greater than 10% by weight based on the weight of the polymer and a polydispersity of 1.175 or less. The polyurethanes exhibit excellent mechanical properties, are highly hygroscopic and cured rapidly.