(2S)-3,5-difluorophenylalaninol | 869657-95-4

• 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: (2S)-3,5-difluorophenylalaninol
• 英文别名: 2-amino-3-(3,5-difluoro-phenyl)-propan-1-ol；(S)-2-Amino-3-(3,5-difluorophenyl)propan-1-OL；(2S)-2-amino-3-(3,5-difluorophenyl)propan-1-ol
• CAS: 869657-95-4
• 化学式: C₉H₁₁F₂NO
• 分子量: 187.189
• InChiKey: ZFNQOFXFLOCCTI-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-3,5-difluorophenylalaninol 在 palladium dihydroxide N-羟基-7-氮杂苯并三氮唑 、 氢气 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 生成 N-[(2S)-1-(3,5-difluorophenyl)-3-hydroxypropan-2-yl]-2-({[(1S,2S)-2-methylcyclopropyl]methyl}amino)-6-(N-methylmethanesulfonamido)pyridine-4-carboxamide
  参考文献：
  名称：

  Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind β-secretase in a N-terminal 10s-loop down conformation

  摘要：

  A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-I inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P-3 which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.051
• 作为产物：
  描述：

  N-叔丁氧羰基-L-3,5-二氟苯丙氨酸 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 (2S)-3,5-difluorophenylalaninol
  参考文献：
  名称：

  Methods of Treatment of Amyloidosis Using Subsituted Ethanolcyclicamine Aspartyl Protease Inhibitors

  摘要：

  这项发明涉及新型化合物和治疗与淀粉样蛋白病相关的疾病、紊乱和症状的方法。淀粉样蛋白病是指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和症状。

  公开号：

  US20080166332A1

文献信息

• ISOINDOLINONE AND PYRROLOPYRIDINONE DERIVATIVES AS AKT INHIBITORS
  申请人：Incyte Corporation

  公开号：US20130096144A1

  公开（公告）日：2013-04-18

  The present invention provides isoindolinone and pyrrolopyridinone derivatives, as well as their compositions and methods of use, that inhibit the activity of the serine/threonine kinase, Akt, and are useful in the treatment of diseases related to the activity of Akt including, for example, cancer and other diseases.

  本发明提供了异吲哚酮和吡咯吡啶酮衍生物，以及它们的组合物和使用方法，这些衍生物抑制丝氨酸/苏氨酸激酶Akt的活性，对于治疗与Akt活性相关的疾病，例如癌症和其他疾病，具有益处。
• Rational Design of Selective and Bioactive Inhibitors of the <i>Mycobacterium tuberculosis</i> Proteasome
  作者：Kyle A. Totaro、Dominik Barthelme、Peter T. Simpson、Xiuju Jiang、Gang Lin、Carl F. Nathan、Robert T. Sauer、Jason K. Sello

  DOI：10.1021/acsinfecdis.6b00172

  日期：2017.2.10

  The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response. Proteasome inhibitors could render Mtb susceptible

  结核分枝杆菌（Mtb）中蛋白酶体的20S核心颗粒是有前途的但非常规的药物靶标。该多聚体肽酶不是必需的，而是通过与宿主免疫应答过程中产生的一氧化氮（和/或相关的反应性氮中间体）反应，降解已受损且有毒的蛋白质。蛋白酶体抑制剂可以使Mtb对免疫系统敏感，但只有在不抑制人类必需的20S对应物的情况下，它们才在治疗上可行。Mtb的选择性抑制剂设计和合成20S是基于其独特的底物偏好和模仿丁香脂素的真核蛋白酶体的模拟底物的共价抑制剂的结构。与亲本丁香脂素不同，设计的类似物弱抑制人类20S（Hs 20S）蛋白酶体，比人类对应物优先抑制Mtb 20S多达74倍。此外，它们可以穿透分枝杆菌的细胞包膜并使Mtb易受一氧化氮介导的压力的影响。重要的是，它们不会在体外抑制人细胞系的生长，因此可能是结核药物开发的起点。
• Methods of Treatment of Amyloidosis Using Subsituted Ethanolcyclicamine Aspartyl Protease Inhibitors
  申请人：Hom Roy

  公开号：US20080166332A1

  公开（公告）日：2008-07-10

  The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein

  这项发明涉及新型化合物和治疗与淀粉样蛋白病相关的疾病、紊乱和症状的方法。淀粉样蛋白病是指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和症状。
• Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines
  作者：Kyle A. Totaro、Dominik Barthelme、Peter T. Simpson、Robert T. Sauer、Jason K. Sello

  DOI：10.1016/j.bmc.2015.07.041

  日期：2015.9

  Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs. (c) 2015 Elsevier Ltd. All rights reserved.
• [EN] METHODS OF TREATMENT OF AMYLOIDOSIS USING ETHANOL CYCLICAMINE DERIVATIVES ASPARTYL PROTEASE INHIBITORS<br/>[FR] METHODES DE TRAITEMENT DE L'AMYLOIDOSE AU MOYEN D'INHIBITEURS D'ASPARTYLE PROTEASE D'ETHANOLAMINE CYCLIQUE
  申请人：ELAN PHARM INC

  公开号：WO2006026533A3

  公开（公告）日：2006-06-08