pentyl-pyridoxamine | 195441-69-1

• 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
• 英文名称: pentyl-pyridoxamine
• 英文别名: 4-(Aminomethyl)-2-methyl-5-(pentoxymethyl)pyridin-3-ol
• CAS: 195441-69-1
• 化学式: C₁₃H₂₂N₂O₂
• 分子量: 238.33
• InChiKey: QYCOVUWHTNVASO-UHFFFAOYSA-N

物化性质

• 熔点：
  118-120 °C
• 沸点：
  422.5±40.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  68.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  pentyl-pyridoxamine 在 盐酸 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Characterization of Scavengers of γ-Ketoaldehydes That Do Not Inhibit Prostaglandin Biosynthesis

  摘要：

  Expression Of cyclooxygenase-2 (COX-2) is associated with the development of many pathologic conditions. The product of COX-2, prostaglandin H(2) (PGH(2)), can spontaneously rearrange to form reactive gamma-ketoaldehydes called levuglandins (LGs). This gamma-keloaldehyde structure confers a high degree of reactivity on the LGs, which rapidly form covalent adducts with primary amines of protein residues. Formation of LG adducts of proteins has been demonstrated in pathologic conditions (e.g., increased levels in the hippocampus in Alzheimer's disease) and during physiologic function (platelet activation). On the basis of knowledge that lipid modification of proteins is known to cause their translocation and to alter their function. we hypothesize that modification of proteins by LG could have functional consequences. Testing this hypothesis requires an experimental approach that discriminates between the effects of protein modification by LG and the, effects of cyclooxygenase-derived prostanoids acting through their G-protein Coupled receptors. TO achieve this goal, we have synthesized and evaluated it series of scavengers that react with LG with a potency More than 2 orders of magnitude greater than that with the epsilon-amine of lysine. A Subset of these scavengers are shown to block the formation of LG adducts of proteins in cells without inhibiting the catalytic activity of the cyclooxygenases. Ten of these selective scavengers did not produce cytotoxicity. These results demonstrate that small molecules can scavenge LGs in cells without interfering with the formation of prostaglandins. They also provide a working hypothesis for the development of pharmacologic agents that could be used in experimental animals in vivo to assess the pathophysiological contribution of levuglandins in diseases associated with cyclooxygenase up-regulation.

  DOI：

  10.1021/tx900407a
• 作为产物：
  描述：

  2-甲基-3-羟基-4,5-二羟甲基吡啶 在 manganese(IV) oxide 、 甲酸 、 盐酸羟胺 、 sodium acetate 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 氯仿 、 丙酮 为溶剂， 反应 3.0h， 生成 pentyl-pyridoxamine
  参考文献：
  名称：

  Characterization of Scavengers of γ-Ketoaldehydes That Do Not Inhibit Prostaglandin Biosynthesis

  摘要：

  Expression Of cyclooxygenase-2 (COX-2) is associated with the development of many pathologic conditions. The product of COX-2, prostaglandin H(2) (PGH(2)), can spontaneously rearrange to form reactive gamma-ketoaldehydes called levuglandins (LGs). This gamma-keloaldehyde structure confers a high degree of reactivity on the LGs, which rapidly form covalent adducts with primary amines of protein residues. Formation of LG adducts of proteins has been demonstrated in pathologic conditions (e.g., increased levels in the hippocampus in Alzheimer's disease) and during physiologic function (platelet activation). On the basis of knowledge that lipid modification of proteins is known to cause their translocation and to alter their function. we hypothesize that modification of proteins by LG could have functional consequences. Testing this hypothesis requires an experimental approach that discriminates between the effects of protein modification by LG and the, effects of cyclooxygenase-derived prostanoids acting through their G-protein Coupled receptors. TO achieve this goal, we have synthesized and evaluated it series of scavengers that react with LG with a potency More than 2 orders of magnitude greater than that with the epsilon-amine of lysine. A Subset of these scavengers are shown to block the formation of LG adducts of proteins in cells without inhibiting the catalytic activity of the cyclooxygenases. Ten of these selective scavengers did not produce cytotoxicity. These results demonstrate that small molecules can scavenge LGs in cells without interfering with the formation of prostaglandins. They also provide a working hypothesis for the development of pharmacologic agents that could be used in experimental animals in vivo to assess the pathophysiological contribution of levuglandins in diseases associated with cyclooxygenase up-regulation.

  DOI：

  10.1021/tx900407a

文献信息

• Scavenging 4-Oxo-2-nonenal
  作者：Venkataraman Amarnath、Kalyani Amarnath

  DOI：10.1021/acs.chemrestox.5b00301

  日期：2015.10.19

  4-Oxo-2-nonenal (ONE), a product of cellular lipid oxidation, reacts nonspecifically with the lysine residues of proteins and is generated in increased amounts during degenerative diseases and cancer. We show that pyridoxamine, salicylamine, and related 2-aminomethylphenols react with ONE, to form pyrrolo[2,1-b][1,3]oxazines with the participation of both the amino and the phenolic groups. 2-Aminomethylphenols react with ONE as well as with the Michael adducts of ONE much more rapidly than lysine, suggesting their use for therapeutically scavenging ONE.

  4-氧代-2-壬烯醛（ONE）是细胞脂质氧化的产物，它能与蛋白质的赖氨酸残基发生非特异性反应，并在退行性疾病和癌症期间产生更多的ONE。我们的研究表明，吡多胺、水杨酸胺和相关的 2-氨基甲基苯酚会与 ONE 发生反应，在氨基和酚基的参与下形成吡咯并[2,1-b][1,3]恶嗪。2- 氨基甲基苯酚与 ONE 以及 ONE 的迈克尔加合物发生反应的速度比赖氨酸快得多，这表明它们可用于清除 ONE。
• Methods of preventing platelet activation
  申请人：Vanderbilt University

  公开号：US10166248B1

  公开（公告）日：2019-01-01

  A method of preventing or reducing the occurrence of malondiadehyde and/or levuglandin protein modification in a subject in need thereof, comprising administering to said subject an effective amount of at least one γ-KA scavenger compound, or a pharmaceutically acceptable salt thereof.

  一种在有需要的受试者中预防或减少丙二醛和/或左旋糖苷蛋白修饰发生的方法，包括向所述受试者施用有效量的至少一种γ-KA清除剂化合物或其药学上可接受的盐。
• Methods for treating inflammation and hypertension with γ-ketoaldehyde skavengers
  申请人：Roberts, II L. Jackson

  公开号：US10975033B2

  公开（公告）日：2021-04-13

  A method of treating at least one of inflammation, psoriasis, and/or hypertension comprising administering to a patient in need there of an effective gamma-ketoaldehyde scavenging amount of a gamma-ketoaldehyde scavenging compound.

  一种治疗炎症、牛皮癣和/或高血压中至少一种疾病的方法，包括向有需要的患者施用有效γ-酮醛清除量的γ-酮醛清除化合物。
• US20140256774A1
  申请人：——

  公开号：US20140256774A1

  公开（公告）日：2014-09-11
• LEVUGLANDIN ADDUCTS HISTONE H4 IN A CYCLOOXYGENASE-2-DEPENDENT MANNER, ALTERING ITS INTERACTION WITH DNA
  申请人：VANDERBILT UNIVERSITY

  公开号：US20150265584A1

  公开（公告）日：2015-09-24

  Method of inhibiting formation of levuglandin adducts of histone and DNA in a subject in need thereof by administering a levuglandin adduct formation inhibiting amount of a compound of the following formula: wherein the variables are defined herein.