6-乙炔烟酸甲酯 | 216444-00-7

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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-乙炔烟酸甲酯
• 中文别名: 6-乙炔基烟酸甲酯
• 英文名称: methyl 6-ethynylnicotinate
• 英文别名: methyl 6-ethynylpyridine-3-carboxylate
• CAS: 216444-00-7
• 化学式: C₉H₇NO₂
• mdl: MFCD16988751
• 分子量: 161.16
• InChiKey: FRIWHMYAJZHCGW-UHFFFAOYSA-N

物化性质

• 沸点：
  249.7±25.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

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

反应信息

• 作为反应物：
  描述：

  6-乙炔烟酸甲酯 在 copper(II) sulfate 、 sodium ascorbate 、 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and evaluation of a ligand targeting the μ and δ opioid receptors for drug delivery to lung cancer

  摘要：

  A well-established approach to developing new imaging agents and treatments for cancer begins with the recognition of receptors that are overexpressed in cancer cells. Ideally, these same receptors would also be absent, or minimally expressed, in healthy tissue. The mu (mu) and delta (delta) opioid receptors (MOR and DOR respectively) match these criteria, with expression in cancer cells that is higher than primary lung epithelial cells. Naltrexone is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence or prevention of relapse from opioid addiction. Since naltrexone binds with high affinity to both MOR and DOR, it was selected as the platform for development of novel ligands capable of delivering a cytotoxic payload to non-small cell lung cancer (NSCLC). This study outlines the synthesis of two ligands, with peptide or PEG linkers that were synthesized from 6-amino-naltrexone and conjugated with rhodamine dye or Tc-99m for in vitro imaging, binding affinity or in vivo imaging and biodistribution studies. Transfected HEK cells were used as a model system for over-expression of the mu-opioid receptor (MOR) or the delta-opioid receptor (DOR). Naltrexone and naltrindole were used as competition for MOR and DOR respectively during the binding affinity studies. Mice bearing a xenograft of HEI( cells transfected with mu (HEK-mu) or delta (HEK-delta) opioid receptors were the animal model used for PET imaging and in vivo biodistribution studies. Although the binding affinity studies were encouraging, the biodistribution data for the selected conjugates lacked sufficient specificity. These conjugates were abandoned from further development but information about their synthesis may be valuable to other laboratories working in this field. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.06.067
• 作为产物：
  描述：

  6-溴烟酸 在 copper(l) iodide 、 PdCl₂(Ph₃)₂ 、 potassium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 乙腈 为溶剂， 生成 6-乙炔烟酸甲酯
  参考文献：
  名称：

  Synthesis and evaluation of a ligand targeting the μ and δ opioid receptors for drug delivery to lung cancer

  摘要：

  A well-established approach to developing new imaging agents and treatments for cancer begins with the recognition of receptors that are overexpressed in cancer cells. Ideally, these same receptors would also be absent, or minimally expressed, in healthy tissue. The mu (mu) and delta (delta) opioid receptors (MOR and DOR respectively) match these criteria, with expression in cancer cells that is higher than primary lung epithelial cells. Naltrexone is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence or prevention of relapse from opioid addiction. Since naltrexone binds with high affinity to both MOR and DOR, it was selected as the platform for development of novel ligands capable of delivering a cytotoxic payload to non-small cell lung cancer (NSCLC). This study outlines the synthesis of two ligands, with peptide or PEG linkers that were synthesized from 6-amino-naltrexone and conjugated with rhodamine dye or Tc-99m for in vitro imaging, binding affinity or in vivo imaging and biodistribution studies. Transfected HEK cells were used as a model system for over-expression of the mu-opioid receptor (MOR) or the delta-opioid receptor (DOR). Naltrexone and naltrindole were used as competition for MOR and DOR respectively during the binding affinity studies. Mice bearing a xenograft of HEI( cells transfected with mu (HEK-mu) or delta (HEK-delta) opioid receptors were the animal model used for PET imaging and in vivo biodistribution studies. Although the binding affinity studies were encouraging, the biodistribution data for the selected conjugates lacked sufficient specificity. These conjugates were abandoned from further development but information about their synthesis may be valuable to other laboratories working in this field. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.06.067

文献信息

• Europium-Based Metal–Organic Framework as a Dual Luminescence Sensor for the Selective Detection of the Phosphate Anion and Fe³⁺ Ion in Aqueous Media
  作者：Purna Chandra Rao、Sukhendu Mandal

  DOI：10.1021/acs.inorgchem.8b02017

  日期：2018.10.1

  europium-based metal–organic framework has been synthesized with the newly designed ligand L (6-[1-(4-carboxyphenyl)-1H-1,2,3-triazol-4-yl]nicotinic acid). This compound acts as a dual sensor for the phosphate anion and Fe3+ ion in aqueous media. The mechanistic aspect of this selectivity and sensitivity was explored through several spectroscopic methods and then correlated with the corresponding structure.

  已经使用新设计的配体L（6- [1-（4-羧基苯基）-1 H -1,2,3-三唑-4-基]烟酸合成了一种新的三维euro基金属有机框架）。该化合物可作为水性介质中磷酸根阴离子和Fe 3+离子的双重传感器。通过几种光谱方法探讨了这种选择性和灵敏度的机理，然后将其与相应的结构相关联。
• TRICYCLIC MGLUR5 RECEPTOR MODULATORS
  申请人：Anthony Neville J.

  公开号：US20130210804A1

  公开（公告）日：2013-08-15

  The present invention is directed to tricyclic compounds which are positive allosteric modulators of metabotropic glutamate receptors, particularly the mGluR5 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及三环化合物，它们是代谢型谷氨酸受体的正向变构调节剂，特别是mGluR5受体，并且它们在治疗或预防与谷氨酸功能障碍相关的神经系统和精神障碍以及代谢型谷氨酸受体参与的疾病中具有用途。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗代谢型谷氨酸受体参与的疾病中的使用。
• Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr⁷⁰⁵/Ser⁷²⁷ Inhibitory Activity for Gastric Cancer Treatment
  作者：Peng He、Ying Miao、Yue Sun、Aiwu Bian、Wangrui Jin、Huang Chen、Jiangnan Ye、Jia He、Yangrui Peng、Haijun Gu、Mingyao Liu、Zhengfang Yi、Yihua Chen

  DOI：10.1021/acs.jmedchem.2c00413

  日期：2022.10.13

  discovery of the best compound 3h (HP590) among the investigated ones, a novel, highly potent, and orally bioavailable STAT3 inhibitor possessing lower nanomolar inhibitory activity toward p-Tyr705 and p-Ser727. Target validation revealed that HP590 selectively targets STAT3 to remarkably inhibit its canonical and noncanonical activation and corresponding biological functions, thereby resulting in the growth

  越来越多的证据表明 STAT3 在 Tyr 705和 Ser 727的磷酸化共同促进了胃癌的发生和进展。然而，大多数报道的 STAT3 抑制剂主要集中在抑制 STAT3 在 Tyr 705的磷酸化，而忽略了在 Ser 727磷酸化的致瘤作用。在此，我们描述了一系列三芳杂环衍生物作为强效双磷酸化 STAT3 抑制剂的设计、合成和构效关系研究。这些努力导致发现了最好的化合物3h ( HP590) 在所研究的药物中，一种新型、高效、可口服的 STAT3 抑制剂对 p-Tyr 705和 p-Ser 727具有较低的纳摩尔抑制活性。靶向验证表明，HP590选择性靶向STAT3，显着抑制其经典和非经典激活及相应的生物学功能，从而在体外和体内抑制胃癌的生长，凸显了双磷酸化STAT3抑制剂对胃癌的治疗潜力。
• Design and Discovery of Novel NLRP3 Inhibitors and PET Imaging Radiotracers Based on a 1,2,3-Triazole-Bearing Scaffold
  作者：Yiming Xu、Yulong Xu、Savannah Biby、Baljit Kaur、Yan Liu、Frederick Andrew Bagdasarian、Hsiao-Ying Wey、Rudolph Tanzi、Can Zhang、Changning Wang、Shijun Zhang

  DOI：10.1021/acs.jmedchem.3c01782

  日期：2024.1.11

  NOD-like receptor (NLR) family pyrin-domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune system, has been emerging as a viable drug target and a potential biomarker for human diseases. In our efforts to develop novel small molecule NLRP3 inhibitors, a 1-(5-chloro-2-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole scaffold was designed via a rational approach based on our previous

  NOD 样受体 (NLR) 家族含热蛋白结构域 3 (NLRP3) 炎性体是先天免疫系统的重要组成部分，已成为可行的药物靶点和人类疾病的潜在生物标志物。在我们努力开发新型小分子NLRP3抑制剂的过程中，基于我们之前的线索，通过合理的方法设计了1-(5-氯-2-甲氧基苄基)-4-苯基-1H-1,2,3-三唑支架。结构-活性关系研究和生物物理学研究确定了一种新的先导化合物8是一种有效的（IC 50 ：0.55 ± 0.16 μM）、选择性和直接的 NLRP3 抑制剂。 [ 11 C] 8的正电子发射断层扫描 (PET) 成像研究表明，其在小鼠和恒河猴中的大脑吸收速度快且高，并且清除速度快。值得注意的是，对恒河猴 PET/磁共振成像研究的这种放射性示踪剂的等离子体动力学分析表明放射性代谢稳定性。总的来说，我们的数据不仅鼓励对该先导化合物的进一步研究，而且还需要进一步优化以产生其他新型 NLRP3
• Novel, highly potent systemic glucokinase activators for the treatment of Type 2 Diabetes Mellitus
  作者：Jiayi Xu、Songnian Lin、Robert W. Myers、George Addona、Joel P. Berger、Brian Campbell、Hsuan-shen Chen、Zhesheng Chen、George J. Eiermann、Nadine H. Elowe、Brian T. Farrer、Wen Feng、Qinghong Fu、Roman Kats-Kagan、Michael Kavana、Sunita Malkani、Daniel R. McMasters、Kaushik Mitra、Michele J. Pachanski、Xinchun Tong、Maria E. Trujillo、Libo Xu、Bei Zhang、Fengqi Zhang、Rui Zhang、Emma R. Parmee

  DOI：10.1016/j.bmcl.2016.10.085

  日期：2017.5

  Glucokinase (GK, hexokinase IV) is a unique hexokinase that plays a central role in mammalian glucose homeostasis. Glucose phosphorylation by GK in the pancreatic beta-cell is the rate-limiting step that controls glucose-stimulated insulin secretion. Similarly, GK-mediated glucose phosphorylation in hepatocytes plays a major role in increasing hepatic glucose uptake and metabolism and possibly lowering hepatic glucose output. Small molecule GK activators (GKAs) have been identified that increase enzyme activity by binding to an allosteric site. GKAs offer a novel approach for the treatment of Type 2 Diabetes Mellitus (T2DM) and as such have garnered much attention. We now report the design, synthesis, and biological evaluation of a novel series of 2,5,6-trisubstituted indole derivatives that act as highly potent GKAs. Among them, Compound 1 was found to possess high in vitro potency, excellent physicochemical properties, and good pharmacokinetic profile in rodents. Oral administration of Compound 1 at doses as low as 0.03 mg/kg led to robust blood glucose lowering efficacy in 3 week high fat diet-fed mice. (C) 2016 Published by Elsevier Ltd.