6-氰基吲哚-2-甲酸乙酯 | 104291-81-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 吲哚类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 6-氰基吲哚-2-甲酸乙酯
• 英文名称: ethyl 6-cyano-1H-indole-2-carboxylate
• 英文别名: ethyl 6-cyanoindole-2-carboxylate；6-cyano-indole-2-carboxylic acid ethyl ester；6-Cyan-indol-2-carbonsaeure-aethylester；6-cyano-1H-indole-2-carboxylic acid ethyl ester
• CAS: 104291-81-8
• 化学式: C₁₂H₁₀N₂O₂
• 分子量: 214.224
• InChiKey: IUCDNWPSPSMAPS-UHFFFAOYSA-N

物化性质

• 熔点：
  171 °C
• 沸点：
  419.3±25.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氰基吲哚-2-甲酸乙酯 在 manganese(IV) oxide 、 锂硼氢 、 titanium(III) chloride 、 lithium 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 丙酮 为溶剂， 反应 56.17h， 生成 (E)-2,2'-Vinylenbis(6-indolcarbonitril)
  参考文献：
  名称：

  Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: Synthesis and SAR of novel analogs of MBX 1066 and MBX 1090

  摘要：

  The prevalence of drug-resistant bacteria in the clinic has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We have previously described a set of bisamidine antibiotics that contains a core composed of two indoles and a central linker. The first compounds of the series, MBX 1066 and MBX 1090, have potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. We have conducted a systematic exploration of the amidine functionalities, the central linker, and substituents at the indole 3-position to determine the factors involved in potent antibacterial activity. Some of the newly synthesized compounds have even more potent and broad-spectrum activity than MBX 1066 and MBX 1090. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.014
• 作为产物：
  描述：

  ethyl 3-(4-cyano-2-nitrophenyl)-2-oxopropionate 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 生成 6-氰基吲哚-2-甲酸乙酯
  参考文献：
  名称：

  [EN] 3-SUBSTITUTED-5- AND 6-AMINOALKYL INDOLE-2-CARBOXYLIC ACID AMIDES AND RELATED ANALOGS AS INHIBITORS OF CASEIN KINASE Ie
  [FR] AMIDES DE L'ACIDE 5- ET 6-AMINOALKYL INDOLE-2-CARBOXYLIQUE SUBSTITUÉ EN POSITION 3 ET ANALOGUES APPARENTÉS EN TANT QU'INHIBITEURS DE LA CASÉINE KINASE I EPSILON

  摘要：

  本发明揭示并声明公式(I)和公式(II)的化合物作为人类酪蛋白激酶Iϵ的抑制剂，并使用公式(I)和公式(II)的这些化合物治疗包括情绪障碍和睡眠障碍在内的中枢神经系统疾病和疾病的方法。还揭示和声明了包含公式(I)或公式(II)化合物的药物组合物。

  公开号：

  WO2006023467A1

文献信息

• Aromatic amidine derivatives useful as selective thrombin inhibitors
  申请人：C & C Research Laboratories

  公开号：US06201006B1

  公开（公告）日：2001-03-13

  The present invention relates to a novel thrombin inhibitor which is effective even when orally administered. More specifically, the present invention relates to an aromatic amidine derivative represented by formula (I) and the salts thereof, which show potent selective inhibitory activity for thrombin in which (a), R, R1, R2, R3, A, W, Y and n are defined as described in the specification.

  本发明涉及一种新颖的凝血酶抑制剂，即使口服给药也有效。更具体地说，本发明涉及一种由公式（I）表示的芳香族酰胺衍生物及其盐，其对凝血酶具有强的选择性抑制活性，其中（a），R，R1，R2，R3，A，W，Y和n如说明书所述定义。
• Preparation and Pharmacological Evaluation of Novel Glycoprotein (Gp) IIb/IIIa Antagonists. 2. Condensed Heterocyclic Derivatives.
  作者：Shin'ichiro ONO、Tomohiro YOSHIDA、Kazuhiro MAEDA、Keigo KOSAKA、Yoshihisa INOUE、Teruaki IMADA、Chikara FUKAYA、Norifumi NAKAMURA

  DOI：10.1248/cpb.47.1694

  日期：——

  A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobanzofuran-2-carboxamido)cyclohexyloxyacetic acid 17e and trans-3-[4-(5-amidinobanzofuran-2-carboxamido)cyclohexyl]propionic acid 17f produced marked inhibitions with IC50 values of 0.018 and 0.006 μM, respectively in a human platelet adenosin-5'-diphospate (ADP)-induced aggregation assay; they also exhibited a wide spectrum of inhibition toward major aggregation agonists (ADP, collagen, thrombin, PMA (tumor promoter) and arachidonic acid). These compounds were >2-3 orders of magnitude more effective in inhibiting platelet aggregation than human umbilical vein endothelial cell (HUVEC) binding. The oral administration of 10 mg/kg of either 17e and 17f to guinea pig, resulted in a 60% inhibition of ex vivo platelet aggregation after 5 h. Oral administration of ethyl trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetate 18e (10 mg/kg) resulted in 80% inhibition of platelet aggregation in dogs for 6 h after oral administration with a return to baseline by 24 h. Ethyl trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionate 18f (AR0598) produced 80% inhibition for 5 h after oral administration. Prodrug 18e showed a good profile in dogs with a long duration of action. 18e (AR0510) was selected as suitable clinical candidate for development as an orally active antithrombotic agent.

  合成了一系列新型的以稠合杂环为基本核心的血小板受体糖蛋白 (Gp) IIb/IIIa 拮抗剂。在体外试验中，反式-4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基) 环己氧乙酸 17e 和反式-3-[4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基)环己基] 丙酸 17f 在人血小板腺苷 -5'- 二磷酸 (ADP) 诱导的聚集试验中分别产生了显著的抑制作用，其 IC50 值分别为 0.018 和 0.006 μM;它们对主要的聚集激动剂 (ADP、胶原蛋白、凝血酶、PMA (肿瘤促进剂) 和花生四烯酸) 也表现出广泛的抑制作用。这些化合物在抑制血小板聚集方面比人脐静脉内皮细胞 (HUVEC) 结合的有效性高出 2-3 个数量级。将 17e 和 17f 以 10 mg/kg 的剂量口服给予豚鼠，5 小时后体外血小板聚集抑制率达到 60%。将反式-4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基) 环己氧乙酸乙酯 18e (10 mg/kg)口服给予狗，6 小时后血小板聚集抑制率达到 80%，24 小时后恢复到基线水平。反式-3-[4-(5- 氨甲酰苯并呋喃 -2- 羧酰胺基)环己基] 丙酸乙酯 18f (AR0598) 在口服给药后产生了 80% 的抑制作用，持续 5 小时。前药 18e 在狗体内显示出良好的特性，具有较长的作用持续时间。因此，18e (AR0510) 被选为适合开发的口服活性抗血栓药物的候选物。
• A ligand-free, copper-catalyzed cascade sequence to indole-2-carboxylic esters
  作者：Stefan G. Koenig、John W. Dankwardt、Yanbing Liu、Hang Zhao、Surendra P. Singh

  DOI：10.1016/j.tetlet.2010.10.035

  日期：2010.12

  A variety of indole-2-carboxylic esters are accessible in yields up to 61% through a ligand-free, copper-catalyzed reaction of a series of commercially available 2-halo aryl aldehydes with benign glycine amidoesters, including the common reagent ethyl acetamidoacetate. This one-pot, three-reaction format allows ready entry to the desired heterocycles from starting substrates in the reactivity order

  通过一系列无市售的2-卤代芳基醛与良性甘氨酸酰胺基酯的无配体铜催化反应，可以得到产率最高为61％的各种吲哚-2-羧酸酯，包括常用试剂乙酰氨基乙酸乙酯。这种一锅三反应的形式可以按照碘>溴⩾氯取代基的反应顺序从起始底物容易地进入所需的杂环。允许使用各种功能组，从而增加了该方法的通用性。
• [EN] 3-SUBSTITUTED-5- AND 6-AMINOALKYL INDOLE-2-CARBOXYLIC ACID AMIDES AND RELATED ANALOGS AS INHIBITORS OF CASEIN KINASE Ie<br/>[FR] AMIDES DE L'ACIDE 5- ET 6-AMINOALKYL INDOLE-2-CARBOXYLIQUE SUBSTITUÉ EN POSITION 3 ET ANALOGUES APPARENTÉS EN TANT QU'INHIBITEURS DE LA CASÉINE KINASE I EPSILON
  申请人：AVENTIS PHARMA INC

  公开号：WO2006023467A1

  公开（公告）日：2006-03-02

  The present invention discloses and claims compounds of formula (I) and formula (II) as inhibitors of human casein kinase Iϵ, and methods of using said compounds of formula (I) and formula (II) for treating central nervous system diseases and disorders including mood disorders and sleep disorders. Pharmaceutical compositions comprising compounds of formula (I) or formula (II) are also disclosed and claimed.

  本发明揭示并声明公式(I)和公式(II)的化合物作为人类酪蛋白激酶Iϵ的抑制剂，并使用公式(I)和公式(II)的这些化合物治疗包括情绪障碍和睡眠障碍在内的中枢神经系统疾病和疾病的方法。还揭示和声明了包含公式(I)或公式(II)化合物的药物组合物。
• [EN] N-CYCLYL-3 - (CYCLYLCARBONYLAMINOMETHYL) BENZAMIDE DERIVATIVES AS RHO KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE N-CYCLYL-3-(CYCLYLCARBONYLAMINOMÉTHYL)BENZAMIDE EN TANT QU'INHIBITEURS DE LA RHO KINASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012006203A1

  公开（公告）日：2012-01-12

  The present invention relates to compounds of formula (I) : and pharmaceutically acceptable salts thereof, wherein R1and R2 are various ring systems. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of Rho Kinase mediated diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及化合物的公式（I）及其药学上可接受的盐，其中R1和R2是不同的环系统。该发明还涉及包括这些化合物的药物组合物，使用这些化合物治疗Rho激酶介导的疾病和障碍的方法，制备这些化合物的方法以及在这些过程中有用的中间体。