6-炔基烟腈 | 1211588-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-炔基烟腈
• 英文名称: 6-ethynylnicotinonitrile
• 英文别名: 6-Ethynylnicotinonitrile；6-ethynylpyridine-3-carbonitrile
• CAS: 1211588-35-0
• 化学式: C₈H₄N₂
• 分子量: 128.133
• InChiKey: AVVLYLFRULTXHA-UHFFFAOYSA-N

物化性质

• 熔点：
  158 °C
• 沸点：
  249.4±25.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

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

反应信息

• 作为反应物：
  描述：

  6-炔基烟腈 在 亚硝酸特丁酯 、 N-甲基苄胺 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以45%的产率得到2,5-二氰基吡啶
  参考文献：
  名称：

  芳基乙炔碳-碳三键断裂合成芳基腈无需金属催化剂

  摘要：

  实现了炔烃的碳-碳三键的裂解，从而在无过渡金属的条件下合成芳腈。大量的末端炔底物经历了这种反应，以中等至良好的产率提供相应的腈，并具有良好的官能团耐受性。

  DOI：

  10.1002/ejoc.201600438
• 作为产物：
  描述：

  2-溴-5-氰基吡啶 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6-炔基烟腈
  参考文献：
  名称：

  包含ADA和DAD三氢键基序的RuII和IrIII配合物：功能材料组装的潜在构造子。

  摘要：

  描述了一系列含有配体L的[Ru II（bpy）2 L]和[Ir（ppy）2 L]配合物的合成和表征，该配合物具有参与三氢键合作用的潜力。L1和L2包含带有二氨基三嗪侧链的吡啶基三唑螯合单元，能够进行供体-受体-供体（DAD）氢键，而L3和L4分别包含靠近N ^ N和N ^ O裂解位点的ADA氢键单元。X射线晶体学分析显示含有Ru II配合物的L1和L2可通过氢键二聚体，而[Ru II（bpy）2 L 4 ]通过扩展的氢键基序组装形成一维链。相比之下，对于L3的Ru II和Ir III配合物，未观察到预期的氢键模式。光谱研究表明，配合物的吸收光谱是由MLCT和LLCT跃迁的组合产生的。Ir III和Ru II配合物的L1和L2配合物在固态发光，似乎氢键合到互补物质上可能会促进其3的调谐ILCT排放。低频拉曼光谱为L4配合物在固态中有序相互作用提供了进一步的证据，这与X射线晶体学的结果一致。

  DOI：

  10.1002/asia.201801748

文献信息

• [EN] CYCLOPROPYL FUSED THIAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE<br/>[FR] DERIVÉS THIAZINE FUSIONNÉS À UN CYCLOPROPYLE UTILISÉS EN TANT QU'INHIBITEURS DE LA BÊTA-SÉCRÉTASE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2018112086A1

  公开（公告）日：2018-06-21

  The present disclosure provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I) wherein variables A, R1, R2, R2', R3, R4, and R5 of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.

  本公开提供了一类新的化合物，用于调节β-分泌酶酶（BACE）活性。这些化合物具有通用的化学式（I），其中化合物（I）的变量A、R1、R2、R2'、R3、R4和R5在此处定义。本公开还提供了包含这些化合物的药物组合物，以及这些化合物和组合物用于治疗与Aβ斑块形成和沉积相关的疾病和/或症状的用途，这些疾病和症状是由BACE的生物活性引起的。这些由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍和其他中枢神经系统疾病。
• Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use
  申请人：AMGEN INC.

  公开号：US10889581B2

  公开（公告）日：2021-01-12

  The present disclosure provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, R1, R2, R2′, R3, R4, and R5 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.

  本公开提供了一类可用于调节β-分泌酶（BACE）活性的新型化合物。这些化合物具有通式 I： 其中式 I 的变量 A、R1、R2、R2′、R3、R4 和 R5 在本文中定义。本公开还提供了包含这些化合物的药物组合物，以及这些化合物和组合物用于治疗与 BACE 的生物活性导致的 Aβ 斑块形成和沉积有关的疾病和/或病症的用途。此类 BACE 介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍和其他中枢神经系统疾病等。
• A novel series of metabotropic glutamate receptor 5 negative allosteric modulators based on a 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine core
  作者：Guillaume Duvey、Benjamin Perry、Emmanuel Le Poul、Sonia Poli、Beatrice Bonnet、Nathalie Lambeng、Delphine Charvin、Tansy Donovan-Rodrigues、Hasnaà Haddouk、Stefania Gagliardi、Jean-Philippe Rocher

  DOI：10.1016/j.bmcl.2013.06.044

  日期：2013.8

  A series of potent non-acetylinic negative allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 NAMs) was developed starting from HTS screening hit 1. Potency was improved via iterative SAR, and physicochemical properties were optimized to deliver orally bioavailable compounds acceptable for in vivo testing. A lead molecule from the series demonstrated dose-dependent activity in the second phase of the rat formalin test from 30 mg/kg, and a preliminary PK/PD relationship was established. (c) 2013 Elsevier Ltd. All rights reserved.
• Antiprotozoal activity of dicationic 3,5-diphenylisoxazoles, their prodrugs and aza-analogues
  作者：Donald A. Patrick、Stanislav A. Bakunov、Svetlana M. Bakunova、Tanja Wenzler、Reto Brun、Richard R. Tidwell

  DOI：10.1016/j.bmc.2013.10.050

  日期：2014.1

  Fifty novel prodrugs and aza-analogues of 3,5-bis(4-amidinophenyl)isoxazole and its derivatives were prepared. Eighteen of the 24 aza-analogues exhibited IC50 values below 25 nM against Trypanosoma brucei rhodesiense or Plasmodium falciparum. Six compounds had antitrypanosomal IC50 values below 10 nM. Twelve analogues showed similar antiplasmodial activities, including three with sub-nanomolar potencies. Forty-four diamidines (including 16 aza-analogues) and the 26 prodrugs were evaluated for efficacy in mice infected with T. b. rhodesiense STIB900. Six diamidines cured 4/4 mice at daily 5 mg/kg intraperitoneal doses for 4 days, giving results far superior to pentamidine and furamidine. One prodrug attained 3/4 cures at daily 25 mg/kg oral doses for 4 days. (C) 2013 Published by Elsevier Ltd.
• Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of DAPI related diamidines
  作者：Abdelbasset A. Farahat、Arvind Kumar、Martial Say、Alaa El-Din M. Barghash、Fatma E. Goda、Hassan M. Eisa、Tanja Wenzler、Reto Brun、Yang Liu、Leah Mickelson、W. David Wilson、David W. Boykin

  DOI：10.1016/j.bmc.2009.12.011

  日期：2010.1

  A novel series of extended DAPI analogues were prepared by insertion of either a carbon-carbon triple bond (16a-d) or a phenyl group (21a, b and 24) at position-2. The new amidines were evaluated in vitro against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a, 16b, 16d, 21a, 21b) exhibited IC50 values against T. b. r. of 9 nM or less which is two to nine folds more effective than DAPI. The same five compounds exhibited IC50 values against P. f. of 5.9 nM or less which is comparable to that of DAPI. The fluorescence properties of these new molecules were recorded, however; they do not offer any advantage over those of DAPI. (C) 2009 Elsevier Ltd. All rights reserved.