3,5-二氟-4-硝基苄醇 | 1123172-89-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3,5-二氟-4-硝基苄醇
• 中文别名: 3,5-二氟-4-硝基苯甲醇
• 英文名称: (3,5-difluoro-4-nitrophenyl)methanol
• 英文别名: (3,5-difluoro-4-nitro-phenyl)-methanol
• CAS: 1123172-89-3
• 化学式: C₇H₅F₂NO₃
• mdl: MFCD18633079
• 分子量: 189.118
• InChiKey: MWMXVSGWUYOLQS-UHFFFAOYSA-N

物化性质

• 沸点：
  327.2±37.0 °C(Predicted)
• 密度：
  1.531±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3,5-二氟-4-硝基苄醇 在 lithium aluminium tetrahydride 、 palladium diacetate 、 三溴化磷 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 甲基叔丁基醚 、 丙酮 为溶剂， 反应 45.5h， 生成 ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate
  参考文献：
  名称：

  Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides

  摘要：

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.

  DOI：

  10.1021/jm300069y
• 作为产物：
  描述：

  3,5-二氟-4-硝基苯腈 在 氯化亚砜 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.5h， 生成 3,5-二氟-4-硝基苄醇
  参考文献：
  名称：

  Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides

  摘要：

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.

  DOI：

  10.1021/jm300069y

文献信息

• AMINOBENZYL-SUBSTITUTED CYCLIC SULFONES USEFUL AS BACE INHIBITORS
  申请人：Briard Emmanuelle

  公开号：US20090054427A1

  公开（公告）日：2009-02-26

  The invention relates to novel heterocyclic compounds of the formula in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their use as medicaments and to medicaments comprising them.

  这项发明涉及到新型杂环化合物的公式，其中所有变量如规范中定义，以自由形式或盐形式存在，以及它们的制备方法，作为药物的用途，以及包含它们的药物。
• Cyclic sulfones with aminobenzyl substitution useful as BACE inhibitors
  申请人：Briard Emmanuelle

  公开号：US20100056490A1

  公开（公告）日：2010-03-04

  The invention relates to novel heterocyclic compounds of the formula in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their use as medicaments and to medicaments comprising them.

  本发明涉及新的杂环化合物，其化学式如下： 其中所有变量的定义如规范中所述，可以是自由形式或盐形式，涉及其制备、用作药物以及包含它们的药物。
• [EN] SMALL MOLECULE INHIBITORS OF KRAS G12C MUTANT<br/>[FR] INHIBITEURS À PETITES MOLÉCULES DE MUTANT DE KRAS G12C
  申请人：MERCK SHARP & DOHME

  公开号：WO2022232318A1

  公开（公告）日：2022-11-03

  Compounds of Formula (I) or (la) or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or (la) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

  式(I)或(la)的化合物或其药学上可接受的盐可以抑制Kirsten大鼠肉瘤(G12C突变体)蛋白，并有望作为治疗剂用于治疗癌症。本发明还提供了包含式(I)或(la)的化合物或其药学上可接受的盐的制药组合物。本发明还涉及使用这些化合物或其药学上可接受的盐在癌症治疗和预防以及为此制备制药的方法。
• CYCLIC SULFONES WITH AMINOBENZYL SUBSTITUTION USEFUL AS BACE INHIBITORS
  申请人：Novartis AG

  公开号：EP2303857A1

  公开（公告）日：2011-04-06
• US8093406B2
  申请人：——

  公开号：US8093406B2

  公开（公告）日：2012-01-10