(E)-methyl 3-(2-amino-4-fluorophenyl)acrylate | 231297-58-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-methyl 3-(2-amino-4-fluorophenyl)acrylate
• 英文别名: methyl (2E)-3-(2′-amino-4′-fluorophenyl)prop-2-enoate；methyl (2E)-3-(2-amino-4-fluorophenyl)acrylate；methyl trans-(2-amino-4-fluoro)cinnamate；methyl (E)-3-(2-amino-4-fluorophenyl)prop-2-enoate
• CAS: 231297-58-8
• 化学式: C₁₀H₁₀FNO₂
• 分子量: 195.193
• InChiKey: OPGGDNWPBIHRFX-HWKANZROSA-N

物化性质

• 沸点：
  318.3±32.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-methyl 3-(2-amino-4-fluorophenyl)acrylate 在 ice 、 水 作用下， 以 四氢呋喃 、 盐酸 为溶剂， 反应 20.0h， 以to give 20.65 g (81%) of a light-yellow amorphous solid的产率得到7-氟-8-甲基-2(1H)-喹啉酮
  参考文献：
  名称：

  Azetidine and piperidine compounds useful as PDE10 inhibitors

  摘要：

  本发明涉及公式（I）所定义的杂环化合物，其中包括氮杂四元环和氮杂五元环化合物，以及含有这些化合物的组合物，以及制备这些化合物及其中间体的过程。本发明还提供了治疗认知障碍或由PDE10抑制所治疗的疾病的方法，例如亨廷顿病、精神分裂症、双相情感障碍、强迫症等。

  公开号：

  US09303028B2
• 作为产物：
  描述：

  4-氟-1-碘-2-硝基苯 在 palladium diacetate 、 铁粉 、 氯化铵 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 (E)-methyl 3-(2-amino-4-fluorophenyl)acrylate
  参考文献：
  名称：

  Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure–activity relationship for anti-inflammatory drug

  摘要：

  Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG) production cascades in the human body. The mechanisms of both the anti-inflammation effects and the side-effects of traditional COX inhibitors are associated with the existence of two COX isoforms. Thus while COX-1 is predominantly expressed ubiquitously and constitutively, and it serves a housekeeping role in processes such as gastrointestinal (GI) mucosa protection, COX-2 is absent or exhibits a low level of expression in most tissues, and is highly upregulated in response to endotoxin, virus, inflammatory or tissue-injury stimuli/signals, and tumour promoter in the various types of organs, tissues, and cells. Furthermore, COX-2 contribution to PGE(2) and PGI(2) production evokes and sustains systemic or peripheral inflammatory disease, but it is not involved in the COX-1-mediated GI tract events. Also, hypersensitivity of aspirin owing to its inhibitory action against COX-1 is a significant concern clinically. Consequently, highly selective COX-2 inhibitors have been needed for the treatment of inflammatory- and inflammation related-diseases that include pyrexia, inflammation, pain, rheumatoid arthritis, osteoarthritis, and cancers. In this study, a series of novel [2-{[(4-substituted or 4,5-disubstituted)-pyridin-2-yl]carbonyl}-(5- or 6-substituted or 5,6-disubstituted)-1H-indol-3-yl]acetic acid analogues was designed, synthesized, and evaluated to identify potent and selective COX-2 inhibitors as potential agents against inflammatory diseases. As significant findings, the present study clarified unique structure activity relationship of the analogues toward potent and selective COX-2 inhibition in vitro, and identified 2-{6-fluoro-2-[4-methyl-2-pridinyl)carbonyl]-1H-indol-3-yl}acetic acid as a potent and selective COX-2 inhibitor in vitro that demonstrated orally potent anti-inflammation efficacy against carrageenan-induced oedema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation model in vivo. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.053

文献信息

• 2,3-substituted indole compounds as anti-inflammatory and analgesic agents
  申请人：——

  公开号：US06608070B1

  公开（公告）日：2003-08-19

  This invention provides a compound of the following formula: or the pharmaceutically acceptable salts thereof wherein Z is OH, C1-6 alkoxy, —NR2R3 or heterocycle; Q is selected from the following: (a) an optionally substituted phenyl, (b) an optionally substituted 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), (c) an optionally substituted 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, (d) an optionally substituted C3-7 cycloalkyl and (e) an optionally substituted benzo-fuzed heterocycle; R1 is hydrogen, C1-4 alkyl or halo; R2 and R3 are independently hydrogen, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy or CN; X is independently selected from H, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino and CN; and n is 0, 1, 2, 3 and 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

  这项发明提供了以下式的化合物： 或其药学上可接受的盐，其中Z为OH、C1-6烷氧基、—NR2R3或杂环；Q从以下中选择：(a) 可选择取代的苯基，(b) 可选择取代的含有一个、两个、三个或四个氮原子的6-成员单环芳基，(c) 可选择取代的含有O、S和N中选择的一个杂原子的5-成员单环芳基，并且除所述杂原子外还可选择含有一个、两个或三个氮原子，(d) 可选择取代的C3-7环烷基和(e) 可选择取代的苯并噻吩杂环；R1为氢、C1-4烷基或卤素；R2和R3独立地为氢、OH、C1-4烷氧基、C1-4烷基或用卤素、OH、C1-4烷氧基或CN取代的C1-4烷基；X独立地从H、卤素、C1-4烷基、卤素取代的C1-4烷基、OH、C1-4烷氧基、卤素取代的C1-4烷氧基、C1-4烷基硫醚、NO2、NH2、二-(C1-4烷基)氨基和CN中选择；n为0、1、2、3和4。 这项发明还提供了一种用于治疗前列腺素参与的医疗状况的药物组合物。
• [EN] AZETIDINE AND PIPERIDINE COMPOUNDS USEFUL AS PDE10 INHIBITORS<br/>[FR] COMPOSÉS D'AZÉTIDINE ET DE PIPÉRIDINE UTILES COMME INHIBITEURS DE PDE10
  申请人：AMGEN INC

  公开号：WO2013188724A1

  公开（公告）日：2013-12-19

  Azetidine and piperidine compounds of formula (I) as defined in the specification, compositions containing them, and processes for preparing such compounds and intermediates thereof. Provided herein also are methods of treating cognitive disorders or diseases treatable by inhibition of PDE10, such as Huntington's Disease, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  Azetidine和piperidine化合物的化学式（I），包含它们的组合物，以及制备这些化合物和其中间体的过程。本文还提供了治疗认知障碍或通过抑制PDE10可治疗的疾病的方法，如亨廷顿病、精神分裂症、双相情感障碍、强迫症等。
• Synthesis of 5-Amino-2,5-dihydro-1<i>H</i>-benzo[<i>b</i>]azepines Using a One-Pot Multibond Forming Process
  作者：Salaheddin A. I. Sharif、Ewen D. D. Calder、Fábio G. Delolo、Andrew Sutherland

  DOI：10.1021/acs.joc.6b01357

  日期：2016.8.5

  to allylic trichloroacetimidates bearing a 2-allylaminoaryl group from readily available 2-iodoanilines combined with a one-pot multibond forming process has allowed the efficient synthesis of a series of 5-amino-2,5-dihydro-1H-benzo[b]azepines. The potential of these compounds as synthetic building blocks was demonstrated by the preparation of a late-stage intermediate of the hyponatremia agent, mozavaptan

  从容易获得的2-碘苯胺与一锅多键形成工艺相结合，可快速获得带有2-烯丙基氨基芳基的烯丙基三氯乙酰亚氨酸酯，从而有效地合成了一系列5-氨基-2,5-二氢-1H-苯并[ b ] ze。制备低钠血症药物莫扎伐普坦的后期中间体证明了这些化合物作为合成构件的潜力。
• Stereoselective construction of deoxy-cruciferane alkaloids by NHC-catalyzed intramolecular annulation of homoenolate with quinazolinone
  作者：Milind M. Ahire、Mahesh D. Pol、Dattatry S. Kavale、Rajesh G. Gonnade、Santosh B. Mhaske

  DOI：10.1039/c9ob01243e

  日期：——

  Chiral N-heterocyclic carbene (NHC)-catalyzed intramolecular [3 + 2] annulation of enals with an unactivated imine moiety of quinazolinone via formal homoenolate cycloaddition has been demonstrated. It is an excellent approach for stereoselective syntheses of deoxy-cruciferane alkaloids comprising a biologically important pyrroloindoline scaffold. Notably, this is the first report on the NHC-catalyzed

  已证明手性N杂环卡宾（NHC）催化的分子内[3 + 2]通过正式的均烯酸酯环加成反应环化带有喹唑啉酮的亚胺部分的烯醛。对于包含生物学上重要的吡咯并二氢吲哚骨架的脱氧-十字花青烷生物碱的立体选择性合成而言，这是一种极好的方法。值得注意的是，这是有关NHC催化的不对称分子内同戊烯酸酯与环状N-酰基am环合的首次报道。
• Azetidine and piperidine compounds useful as PDE10 inhibitors
  申请人：Amgen Inc.

  公开号：US08691986B2

  公开（公告）日：2014-04-08

  Azetidine and piperidine compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds and intermediates thereof. Provided herein also are methods of treating cognitive disorders or diseases treatable by inhibition of PDE10, such as Huntington's Disease, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  本发明提供了式(I)所定义的氮杂环化合物，包括氮杂四元环和氮杂五元环化合物，以及含有它们的组合物，以及制备这些化合物和中间体的方法。本发明还提供了治疗认知障碍或通过抑制PDE10可治疗的疾病的方法，例如亨廷顿病、精神分裂症、躁郁症、强迫症等。