3-(quinolin-3-yl)acrylic acid | 67752-27-6

• 物质功能分类: 医药中间体 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-(quinolin-3-yl)acrylic acid
• 英文别名: 3-quinolineacrylic acid；3-(quinolin-3-yl)-acrylic acid；3-quinolin-3-yl-acrylic acid；3-(3-quinolyl)-2-propenoate；3-quinolin-3-ylprop-2-enoic acid
• CAS: 67752-27-6
• 化学式: C₁₂H₉NO₂
• 分子量: 199.209
• InChiKey: YBIWIEFOLKWDNV-UHFFFAOYSA-N

物化性质

• 沸点：
  394.8±17.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)
• 稳定性/保质期：

  远离氧化物、光和热。

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090
• 储存条件：
  存放在密封容器中，并置于阴凉、干燥处。请确保储存地点远离氧化剂，避免阳光直射，在室内常温下保存。

反应信息

• 作为反应物：
  描述：

  3-(quinolin-3-yl)acrylic acid 在 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 dichlorormethane 为溶剂， 反应 2.17h， 生成 N-(cyclohexylmethyl)-3-quinolin-3-ylpropanamide
  参考文献：
  名称：

  From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)

  摘要：

  Using fragment-based screening of a focused fragment library, 2-aminoquinoline I was identified as an initial hit for BACE1. Further SAR development was supported by X-ray structures of BACE1 cocrystallized with various ligands and molecular modeling studies to expedite the discovery of potent compounds. These strategies enabled us to integrate the C-3 side chain on 2-aminoquinoline 1 extending deep into the P2' binding pocket of BACE1 and enhancing the ligand's potency. We were able to improve the BACE1 potency to subnanomolar range, over 10(6)-fold more potent than the initial hit (900 mu M). Further elaboration of the physical properties of the lead compounds to those more consistent with good blood-brain barrier permeability led to inhibitors with greatly improved cellular activity and permeability. Compound 59 showed an IC50 value of 11 nM on BACE1 and cellular activity of 80 nM, This compound was advanced into rat pharmacokinetic and pharmacodynamic studies and demonstrated significant reduction of A beta levels in cerebrospinal fluid (CSF).

  DOI：

  10.1021/jm200544q
• 作为产物：
  描述：

  3-喹啉甲醛 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.17h， 生成 3-(quinolin-3-yl)acrylic acid
  参考文献：
  名称：

  From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)

  摘要：

  Using fragment-based screening of a focused fragment library, 2-aminoquinoline I was identified as an initial hit for BACE1. Further SAR development was supported by X-ray structures of BACE1 cocrystallized with various ligands and molecular modeling studies to expedite the discovery of potent compounds. These strategies enabled us to integrate the C-3 side chain on 2-aminoquinoline 1 extending deep into the P2' binding pocket of BACE1 and enhancing the ligand's potency. We were able to improve the BACE1 potency to subnanomolar range, over 10(6)-fold more potent than the initial hit (900 mu M). Further elaboration of the physical properties of the lead compounds to those more consistent with good blood-brain barrier permeability led to inhibitors with greatly improved cellular activity and permeability. Compound 59 showed an IC50 value of 11 nM on BACE1 and cellular activity of 80 nM, This compound was advanced into rat pharmacokinetic and pharmacodynamic studies and demonstrated significant reduction of A beta levels in cerebrospinal fluid (CSF).

  DOI：

  10.1021/jm200544q

文献信息

• Heteroarylacrylamides and their use as pharmaceuticals for the stimulation of the expression of endothelial NO synthase
  申请人：sanofi-aventis

  公开号：EP1939180A1

  公开（公告）日：2008-07-02

  The present invention relates to heteroarylacrylamides of the formula I, in which Het, X, Ra, Rb, R1, R2 and R3 have the meanings indicated in the claims, which modulate the transcription of endothelial nitric oxide (NO) synthase and are valuable pharmacologically active compounds. Specifically, the compounds of the formula I upregulate the expression of the enzyme endothelial NO synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention further relates to processes for the preparation of compounds of the formula I, to pharmaceutical compositions comprising them, and to the use of compounds of the formula I for the manufacture of a medicament for the stimulation of the expression of endothelial NO synthase or for the treatment of various diseases including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency, for example.

  本发明涉及式I的杂环丙烯酰胺， 其中Het、X、Ra、Rb、R1、R2和R3具有权利要求中所示的含义，这些化合物调节内皮型一氧化氮（NO）合酶的转录，并且是有价值的药理活性化合物。具体地，式I的化合物上调内皮型一氧化氮合酶的表达，并可应用于需要增加该酶的表达或增加NO水平或恢复降低的NO水平的情况。本发明还涉及制备式I化合物的方法，包括它们的药物组合物，以及利用式I化合物制造用于刺激内皮型一氧化氮合酶表达或治疗各种疾病的药物，包括心血管疾病，如动脉粥样硬化、血栓形成、冠状动脉疾病、高血压和心脏功能不全等。
• Preparation of quinoline-substituted carbonate and carbamate derivatives
  申请人：——

  公开号：US20020013468A1

  公开（公告）日：2002-01-31

  The invention relates to a process for preparing quinoline-substituted carbonate and carbamate compounds, which are important intermediates in the synthesis of 6-O-substituted macrolide antibiotics. The process employs metal-catalyzed coupling reactions to provide a carbonate or carbamate of formula (I) or (II) or a substrate that can be reduced to obtain the same.

  该发明涉及一种制备喹啉取代碳酸酯和氨基甲酸酯化合物的过程，这些化合物是合成6-O取代大环内酯抗生素的重要中间体。该过程利用金属催化的偶联反应来提供式(I)或(II)的碳酸酯或氨基甲酸酯，或者可以还原得到相同化合物的底物。
• 一种8-氮杂香豆素的合成方法及其在抗肿瘤 药物中的应用
  申请人：天津科技大学

  公开号：CN106810560B

  公开（公告）日：2019-03-01

  本发明涉及一种8‑氮杂香豆素的合成方法，具体是：以3‑取代的吡啶或喹啉氮氧化物为原料，乙酸酐为溶剂，碳酸钾为碱，加热条件下，反应得到8‑氮杂香豆素类化合物。该方法具有操作简便，试剂便宜易得，反应选择性高，底物适用性广，产率高等优点。本发明首次运用该方法得到了一系列8‑氮杂香豆素类化合物，在建立该类化合物库的合成应用方面具有广阔的前景。在合成的8‑氮杂香豆素类化合物中选取几个进行了体外肿瘤细胞抑制活性的测试，实验发现对人白血病细胞(K562)及肝癌细胞(HepG2)有抑制活性。
• [EN] P-GLYCOPROTEIN INHIBITOR, METHOD FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] INHIBITEUR DE GLYCOPROTEINE P, SON PROCEDE DE PREPARATION ET COMPOSITION PHARMACEUTIQUE COMPORTANT UN TEL INHIBITEUR
  申请人：HANMI PHARM IND CO LTD

  公开号：WO2005033097A1

  公开（公告）日：2005-04-14

  The bioavailability of an anticancer agent is enhanced when the anticancer agent is administered together with a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

  当抗癌药物与公式（I）的化合物或其药学上可接受的盐一起组成药物组合物时，抗癌药物的生物利用度得到增强。
• Substituted isocytosines having histamine H.sub.2 -antagonist activity
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04154834A1

  公开（公告）日：1979-05-15

  The compounds are substituted isocytosines which are histamine H.sub.2 -antagonists. Two specific compounds of the present inventon are 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-5-(3-pyridylmethyl)-4-py rimidone and 2-[2-(3-bromo-2-pyridylmethylthio)ethylamino]-5-(4-pyridylmethyl)-4-pyrimi done.

  这些化合物是取代的异胞嘧啶，是组胺H.sub.2-拮抗剂。本发明的两种特定化合物是2-[2-(5-甲基-4-咪唑基甲硫基)乙基氨基]-5-(3-吡啶甲基)-4-吡咯酮和2-[2-(3-溴-2-吡啶甲硫基)乙基氨基]-5-(4-吡啶甲基)-4-吡咯酮。