3-chloro-N-(pyridin-2-yl)propanamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-chloro-N-(pyridin-2-yl)propanamide
• 英文别名: 3-chloro-N-pyridin-2-ylpropanamide
• 化学式: C₈H₉ClN₂O
• mdl: MFCD01213644
• 分子量: 184.625
• InChiKey: FDYLLPDWPNJJFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-N-(pyridin-2-yl)propanamide 在 甲醇 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 9.5h， 生成 [3-Oxo-3-(pyridin-2-ylamino)propyl]phosphonic acid
  参考文献：
  名称：

  Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors

  摘要：

  DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.076
• 作为产物：
  描述：

  2-氨基吡啶 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 3-chloro-N-(pyridin-2-yl)propanamide
  参考文献：
  名称：

  N-苄基化的（N-芳基氨基甲酰基）烷基膦酸衍生物的合成和抗疟活性。

  摘要：

  已经制备了一系列新颖且易于获得的N-苄基化（N-芳基氨基甲酰基）烷基膦酸酯和相关化合物作为潜在的抗疟剂。生物测定法表明，这些化合物中的一些对恶性疟原虫表现出有希望的活性，并且对HeLa细胞没有明显的生长抑制作用。

  DOI：

  10.1016/j.bmc.2016.04.021

文献信息

• New Insights into the Opioid Analgesic Profile of cis-(−)-N-Normetazocine-derived Ligands
  作者：Giuliana Costanzo、Rita Turnaturi、Carmela Parenti、Salvatore Spoto、Silvia Piana、Maria Dichiara、Chiara Zagni、Anna Rita Galambos、Nariman Essmat、Agostino Marrazzo、Emanuele Amata、Mahmoud Al-Khrasani、Lorella Pasquinucci

  DOI：10.3390/molecules28124827

  日期：——

  In this work, we report on the in vitro and in vivo pharmacological properties of LP1 analogs to complete the series of structural modifications aimed to generate compounds with improved analgesia. To do that, the phenyl ring in the N-substituent of our lead compound LP1 was replaced by an electron-rich or electron-deficient ring and linked through a propanamide or butyramide spacer at the basic nitrogen of the (−)-cis-N-normetazocine skeleton. In radioligand binding assays, compounds 3 and 7 were found to display nanomolar binding affinity for the μ opioid receptor (MOR) (Ki = 5.96 ± 0.08 nM and 1.49 ± 0.24 nM, respectively). In the mouse vas deferens (MVD) assay, compound 3 showed an antagonist effect against DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin), a highly selective MOR prototype agonist, whereas compound 7 produced naloxone reversible effect at MOR. Moreover, compound 7, as potent as LP1 and DAMGO at MOR, was able to reduce thermal and inflammatory pain assessed by the mouse tail-flick test and rat paw pressure thresholds (PPTs) measured by a Randall–Selitto test.

  在这项工作中，我们报告了 LP1 类似物的体外和体内药理特性，以完成一系列结构改造，生成具有更好镇痛效果的化合物。为此，我们将先导化合物 LP1 N-取代基中的苯基环替换为富电子或缺电子环，并通过丙酰胺或丁酰胺间隔物连接 (-)-cis-N-normetazocine 骨架的基氮。在放射性配体结合试验中，发现化合物 3 和 7 与 μ 阿片受体（MOR）的结合亲和力为纳摩尔级（Ki = 5.96 ± 0.08 nM 和 1.49 ± 0.24 nM）。在小鼠输精管（MVD）试验中，化合物 3 对高选择性 MOR 原型激动剂 DAMGO（[D-Ala2, N-MePhe4, Gly-ol]-enkephalin）显示出拮抗作用，而化合物 7 则对 MOR 产生纳洛酮可逆作用。此外，化合物 7 与 LP1 和 DAMGO 对 MOR 的作用一样强，能够减轻通过小鼠尾搔试验评估的热痛和炎症性疼痛，以及通过兰德尔-塞利托试验测量的大鼠爪压阈值（PPTs）。
• Bechstein, Ute; Liebscher, Juergen, Journal fur praktische Chemie (Leipzig 1954), 1989, vol. 331, # 1, p. 153 - 156
  作者：Bechstein, Ute、Liebscher, Juergen

  DOI：——

  日期：——
• Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
  作者：Taryn Bodill、Anne C. Conibear、Marius K.M. Mutorwa、Jessica L. Goble、Gregory L. Blatch、Kevin A. Lobb、Rosalyn Klein、Perry T. Kaye

  DOI：10.1016/j.bmc.2013.04.076

  日期：2013.7

  DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives
  作者：Christiana M. Adeyemi、Faridoon、Michelle Isaacs、Dumisani Mnkandhla、Heinrich C. Hoppe、Rui W.M. Krause、Perry T. Kaye

  DOI：10.1016/j.bmc.2016.04.021

  日期：2016.12

  A series of novel and readily accessible N-benzylated (N-arylcarbamoyl)alkylphosphonate esters and related compounds have been prepared as potential antimalarial agents. Bioassays reveal that some of these compounds exhibit promising activity against Plasmodium falciparum, and exhibit no significant growth inhibition of HeLa cells.

  已经制备了一系列新颖且易于获得的N-苄基化（N-芳基氨基甲酰基）烷基膦酸酯和相关化合物作为潜在的抗疟剂。生物测定法表明，这些化合物中的一些对恶性疟原虫表现出有希望的活性，并且对HeLa细胞没有明显的生长抑制作用。