3-氨基-2,6-二氟苯乙酸甲酯 | 361336-80-3

• 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-氨基-2,6-二氟苯乙酸甲酯
• 英文名称: methyl 2-(3-amino-2,6-difluorophenyl)acetate
• 英文别名: methyl (3-amino-2,6-difluorophenyl)acetate；methyl 3-amino-2,6-difluorophenylacetate
• CAS: 361336-80-3
• 化学式: C₉H₉F₂NO₂
• 分子量: 201.173
• InChiKey: ROSSYYRWJGVZJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  3-氨基-2,6-二氟苯乙酸甲酯 在 potassium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[3-(2-anilino-8-methyl-7-oxopyrido[2,3-d]pyrimidin-6-yl)-2,4-difluorophenyl]propane-1-sulfonamide
  参考文献：
  名称：

  The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-RafV600E kinase

  摘要：

  Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.015
• 作为产物：
  描述：

  2-(2,6-二氟-3-硝基苯基)乙酸 在 吡啶 、 草酰氯 、 铁粉 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-氨基-2,6-二氟苯乙酸甲酯
  参考文献：
  名称：

  Synthesis and Crystal Structures of Substituted Benzenes and Benzoquinones as Tissue Factor VIIa Inhibitors

  摘要：

  Several multistep syntheses of substituted benzenes are reported. The benzene analogues were designed such that their substitution pattern would occupy and interact with the S-1, S-2, and S-3 pockets of the tissue Factor VIIa enzyme. A variety of chemical transformations including nucleophilic additions, reductive aminations, Stille couplings, and polymer-assisted solution-phase (PASP) techniques were used to prepare key intermediates and final products. The initial analogues identified some weakly active compounds which ultimately led to a 340 nM (IC50) tissue Factor VIIa inhibitor with selectivity over other related enzymes. The structure-activity relationship of these inhibitors and the synthetic progression from the discovery of the lead compound to the development of potent analogues will be discussed. The X-ray crystal structures of fluorobenzene 50c and benzoquinone 54 inhibitors complexed with the TF/VIIa enzyme will also be described.

  DOI：

  10.1021/jm030233b

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020193398A1

  公开（公告）日：2002-12-19

  Compounds of the invention are useful in inhibiting thrombin and treating blood coagulation and cardiovascular disorders and have the following structure: 1 wherein R 3 is hydrogen or halogen, and u is N or CH.

  该发明的化合物在抑制凝血酶、治疗血液凝固和心血管疾病方面具有用处，并具有以下结构： 1 其中 R 3 为氢或卤素，u为N或CH。
• [EN] 1,6-NAPHTHYRIDINE COMPOUNDS AND METHODS FOR CSK MODULATION AND INDICATIONS THEREFOR<br/>[FR] COMPOSÉS DE 1,6-NAPHTYRIDINE ET PROCÉDÉS DE MODULATION DE CSK ET LEURS INDICATIONS
  申请人：PLEXXIKON INC

  公开号：WO2021202900A1

  公开（公告）日：2021-10-07

  Disclosed are compounds of Formula (I) or a pharmaceutically acceptable salt, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein R1, R2, R3, R4, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

  揭示了公式（I）的化合物或其药学上可接受的盐、互变异构体、立体异构体或氘代物，其中R1、R2、R3、R4和G如本公开说明书中所述的任何实施方式中描述的一样；以及这些化合物的组合物和用途。
• [EN] NEW ARYL-PYRIDO-PYRIMIDIN-ONE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'ARYL-PYRIDO-PYRIMIDIN-ONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2022129260A1

  公开（公告）日：2022-06-23

  The invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein n, R1, R2, R3, R4and R5are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

  本发明涉及公式（I）的化合物或其药学上可接受的盐，其中n，R1，R2，R3，R4和R5如定义所述并在权利要求书中。公式（I）的化合物可用作药物。
• Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade
  申请人：——

  公开号：US20020025947A1

  公开（公告）日：2002-02-28

  The invention relates to polycyclic aryl and heteroaryl substituted benzene compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

  本发明涉及可用作凝血级联丝氨酸蛋白酶抑制剂的多环芳基和杂芳基取代苯化合物，以及用于治疗和预防包括冠状动脉和脑血管疾病在内的各种血栓性疾病的抗凝疗法的化合物、组合物和方法。
• Design, synthesis and biological evaluation of non-covalent AmpC β-lactamases inhibitors
  作者：Filippo Genovese、Sandra Lazzari、Ettore Venturi、Luca Costantino、Jesus Blazquez、Claudia Ibacache-Quiroga、Maria Paola Costi、Donatella Tondi

  DOI：10.1007/s00044-017-1809-x

  日期：2017.5

  Bacterial resistance represents a worldwide emergency threatening the efficacy of all available antibiotics. Among the several resistance mechanisms developed by bacteria, beta-lactamase enzymes (BLs), which are able to inactivate most beta-lactam core antibiotics, represent a key target to block, thus prolonging antibiotics half-life. Several approaches aimed at inhibiting beta-lactamases have been so far undertaken, mainly involving beta-lactam-like or covalent inhibitors. Applying a structure-based de novo design approach, we recently discovered a novel, non-covalent and competitive inhibitor of AmpC beta-lactamase: lead 1. It has a K-i of 1 mu M, a ligand efficiency of 0.38 kcal mol(-1) and lead-like physical properties. Moreover, it reverts resistance to ceftazidime in bacterial pathogens expressing AmpC and does not up-regulate beta-lactamases expression in cell culture. Its features make it a good candidate for chemical optimization: starting from lead 1 crystallographic complex with AmpC, 11 analogs were designed to complement additional AmpC sites, then synthesized and tested against clinically resistant pathogens. While the new inhibitors maintain similar in vitro activity as the starting lead, some of them, in biological assays, extert a higher potency showing improved synergic activity with ceftazidime in resistant clinically isolated strains.