O-(ethoxycarbonyl)benzohydroxamamide | 54752-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O-(ethoxycarbonyl)benzohydroxamamide
• 英文别名: [(E)-[amino(phenyl)methylidene]amino] ethyl carbonate
• CAS: 54752-10-2
• 化学式: C₁₀H₁₂N₂O₃
• 分子量: 208.217
• InChiKey: DQWWAUALEZIYHR-UHFFFAOYSA-N

物化性质

• 熔点：
  118-122 °C
• 沸点：
  267.9±23.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-(ethoxycarbonyl)benzohydroxamamide 在 溶剂黄146 、 sodium hydroxide 作用下， 以87.5%的产率得到3-苯基-5-羟基-1,2,4-噁二唑
  参考文献：
  名称：

  基于双（异羟肟酸）的新型双功能螯合剂，用于 99mTc 标记多肽

  摘要：

  本文描述了一种基于双（异羟肟酸）的新型双功能螯合剂 (BCA) 的合成和生物学评价，用于 99mTc 标记多肽。我们成功设计并合成了 C3(BHam)2-COOH 作为一种新的 BCA。C3(BHam)2-COOH 形成了稳定的 99mTc 复合物，使我们能够使用 C3(BHam)2-COOH 的 2,3,5,6-四氟苯酚 (TFP) 活性酯制备 99mTc 标记的多肽。用 C3(BHam)2-TFP 制备的 99mTc-C3(BHam)2-HSA 在鼠血浆和过量的 l-半胱氨酸中都是稳定的，99mTc 不会从多肽上解离。此外，小鼠体内 99mTc-C3(BHam)2-HSA 的血液清除率与 125I-HSA 相似，表明 C3(BHam)2-COOH 在体内保持 99mTc 与多肽之间的稳定结合。当 99mTc-C3(BHam)2-NGA 被注射到小鼠体内时，放射性显示早期肝脏摄取高，从肝脏快速清除，表明

  DOI：

  10.1002/jlcr.1954
• 作为产物：
  描述：

  苯甲腈 在 盐酸羟胺 、 碳酸氢钠 、 三乙胺 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 25.0h， 生成 O-(ethoxycarbonyl)benzohydroxamamide
  参考文献：
  名称：

  Discovery of novel heterocyclic derivatives containing oxadiazolone or pyrimidinone cores as DPP‐4 inhibitors

  摘要：

  Type 2 diabetes is a chronic disease characterized by insulin resistance and alterations in incretin secretion, such as the glucagon‐like peptide‐1 (GLP‐1) hormone. GLP‐1 plays a crucial role in signaling insulin production in the pancreas, with its activity regulated by the dipeptidyl peptidase 4 (DPP‐4) enzyme. DPP‐4 presents an intriguing strategy for controlling type 2 diabetes. This study focuses on synthesizing 22 novel oxadiazolone and pyrimidinone derivatives, in vitro DPP‐4 inhibition, and elucidating binding modes through molecular docking simulations. Nine compounds showed promising inhibitory activity, with IC₅₀ values ranging from 0.3 to 1.86 mM. Molecular docking simulations revealed interactions between these compounds and critical residues in the enzyme's active site, such as Arg125, Glu206, Ser630, and His740. This investigation introduces a new class of DPP‐4 inhibitors, providing insights into the design of more potent molecules as potential candidates for combating type 2 diabetes. The findings contribute to developing innovative therapeutics for managing this prevalent metabolic disorder.

  DOI：

  10.1002/jhet.4811

文献信息

• A novel bifunctional chelating agent based on bis(hydroxamamide) for 99mTc labeling of polypeptides
  作者：Masahiro Ono、Masatsugu Ohgami、Mamoru Haratake、Hideo Saji、Morio Nakayama

  DOI：10.1002/jlcr.1954

  日期：2012.2

  This paper describes the synthesis and biological evaluation of a novel bifunctional chelating agent (BCA) based on bis(hydroxamamide) for 99mTc labeling of polypeptides. We successfully designed and synthesized C3(BHam)2―COOH as a new BCA. C3(BHam)2―COOH formed a stable 99mTc complex and enabled us to prepare 99mTc-labeled polypeptides by using a 2,3,5,6-tetrafluorophenol (TFP) active ester of C3(BHam)2―COOH

  本文描述了一种基于双（异羟肟酸）的新型双功能螯合剂 (BCA) 的合成和生物学评价，用于 99mTc 标记多肽。我们成功设计并合成了 C3(BHam)2-COOH 作为一种新的 BCA。C3(BHam)2-COOH 形成了稳定的 99mTc 复合物，使我们能够使用 C3(BHam)2-COOH 的 2,3,5,6-四氟苯酚 (TFP) 活性酯制备 99mTc 标记的多肽。用 C3(BHam)2-TFP 制备的 99mTc-C3(BHam)2-HSA 在鼠血浆和过量的 l-半胱氨酸中都是稳定的，99mTc 不会从多肽上解离。此外，小鼠体内 99mTc-C3(BHam)2-HSA 的血液清除率与 125I-HSA 相似，表明 C3(BHam)2-COOH 在体内保持 99mTc 与多肽之间的稳定结合。当 99mTc-C3(BHam)2-NGA 被注射到小鼠体内时，放射性显示早期肝脏摄取高，从肝脏快速清除，表明
• Kinetics of Methanolysis of Substituted Benzamide O-(Phenoxycarbonyl)- and O-(Alkoxycarbonyl)oximes Catalyzed by Sodium Methanolate
  作者：Libor Dušek、Jaromír Kaválek、Vojeslav Štěrba

  DOI：10.1135/cccc19990265

  日期：——

  The kinetics of methanolysis of substituted benzamide O-(phenoxycarbonyl)- and O-(alkoxycarbonyl)oximes catalyzed by sodium methanolate was studied at 25 °C. The reaction proceeds in two steps. In the first, faster step, the substituted phenoxy group is exchanged for a methoxy group giving rise to substituted O-(methoxycarbonyl)oximes. In the second step, a benzamide oxime is eliminated and dimethyl carbonate is formed. The slope of the plot of the rate constant in dependence on the sodium methanolate concentration has an increasing tendency in both steps. In the presence of 18-crown-6, the plots are linear and the rate constants are lower than in the absence of the crown ether. The rate constants of the reaction of the substrate with the methanolate ion and with the MeONa ion pair were determined assuming that the sodium cation-catalyzed reactions constitute the rate-determining step of the reaction of the substrate with the MeONa ion pair. For the elimination of the aryloxy group and of the substituted benzamide oxime, the rate constants of the reaction with the ion pair are roughly twelvefold and twentyfold higher, respectively, than in the uncatalyzed reaction. The slope of the dependence of log k on the pK_a of the substituted phenols (β_lg) has the value of -0.52 for the uncatalyzed reaction of elimination of the substituted phenoxy group, -0.83 for the elimination of the benzamide oxime group, and -0.53 for the reaction with the ion pair. In the first step and probably also in the second step, the reaction proceeds by the concerted mechanism. The relatively high ρ value of methanolysis of substituted benzamide O-(4-nitrophenoxycarbonyl)oximes, 0.63, suggests that the structure of the transition state approaches that of the tetrahedral intermediate.

  对苯甲酰胺取代物的甲醇解反应动力学，如在25°C下由甲醇酸钠催化的O-(苯氧羰基)-和O-(烷氧羰基)肟进行了研究。该反应分为两步。在第一步中，取代苯氧基被交换成甲氧基，形成取代的O-(甲氧羰基)肟，这是一个较快的步骤。在第二步中，苯甲酰胺肟被消除，生成二甲基碳酸酯。在两个步骤中，速率常数与甲醇酸钠浓度的关系图的斜率均呈增加趋势。在18-冠-6的存在下，图形是线性的，速率常数比没有冠醚存在时更低。假设钠阳离子催化的反应构成了与MeONa离子对反应的反应速率决定步骤，确定了底物与甲醇酸钠离子对反应的速率常数。对于芳氧基和取代苯甲酰胺肟的消除，与离子对反应的速率常数分别比非催化反应高大约12倍和20倍。对于取代酚的pKa的对数值(βlg)的依赖关系的斜率，未催化消除取代苯氧基反应的值为-0.52，消除苯甲酰胺肟基团的值为-0.83，与离子对反应的值为-0.53。在第一步和可能也在第二步中，反应通过协同机制进行。对于取代苯甲酰胺O-(4-硝基苯氧羰基)肟的甲醇解反应的相对较高的ρ值，0.63，表明过渡态的结构接近四面体中间体的结构。
• Amide Compound
  申请人：Matsumoto Takahiro

  公开号：US20080312226A1

  公开（公告）日：2008-12-18

  There is provided a FAAH inhibitor and a prophylactic or therapeutic agent for cerebrovascular disorders or sleep disorders comprising it. The prophylactic or therapeutic agent comprises a compound of the formula (I 0 ): R 1 —C—R 2 —R 3 —R 4 (I 0 ) wherein Z is oxygen or sulfur; R 1 is aryl which may be substituted, or a heterocyclic group which may be substituted; R 1a is a hydrogen atom, a hydrocarbon group which may be substituted, hydroxyl, etc.; R 2 is piperidin-1,4-diyl which may be substituted, or piperazin-1,4-diyl which may be substituted; R 3 is a group formed by eliminating two hydrogen atoms from a 5-membered aromatic heterocyclic group having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, which may be further substituted, —CO—, etc.; and R 4 is a hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; or a salt thereof.

  提供了一种FAAH抑制剂和预防或治疗脑血管疾病或睡眠障碍的药物，其中预防或治疗剂包括化合物(I0)的一种：R1-C-R2-R3-R4(I0)，其中Z为氧或硫；R1为芳基，可以被取代，或者是可以被取代的杂环基；R1a为氢原子，可以被取代的碳氢基，羟基等；R2为可以被取代的哌啶-1,4-二基，或者可以被取代的哌嗪-1,4-二基；R3为从具有1到3个氮、氧和硫杂原子的5元芳香杂环基中消除两个氢原子形成的基团，可以进一步被取代，-CO-等；R4为可以被取代的碳氢基或者可以被取代的杂环基；或其盐。
• Amide compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07851473B2

  公开（公告）日：2010-12-14

  There is provided a FAAH inhibitor and a prophylactic or therapeutic agent for cerebrovascular disorders or sleep disorders comprising it. The prophylactic or therapeutic agent comprises a compound of the formula (I0): wherein Z is oxygen or sulfur; R1 is aryl which may be substituted, or a heterocyclic group which may be substituted; R1a is a hydrogen atom, a hydrocarbon group which may be substituted, hydroxyl, etc.; R2 is piperidin-1,4-diyl which may be substituted, or piperazin-1,4-diyl which may be substituted; R3 is a group formed by eliminating two hydrogen atoms from a 5-membered aromatic heterocyclic group having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, which may be further substituted, —CO—, etc.; and R4 is a hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; or a salt thereof.

  提供了一种FAAH抑制剂和用于预防或治疗脑血管疾病或睡眠障碍的预防性或治疗性制剂，它包括公式（I0）的化合物：其中Z是氧或硫；R1是取代的芳基或取代的杂环基；R1a是氢原子、可取代的碳氢基、羟基等；R2是可取代的哌啶-1,4-二基或可取代的哌嗪-1,4-二基；R3是由1至3个从氮、氧和硫中选择的杂原子构成的5-成员芳香杂环基消去两个氢原子形成的基团，它可以进一步取代，-CO-等；R4是可取代的碳氢基或可取代的杂环基；或其盐。
• AMIDE COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1813606A1

  公开（公告）日：2007-08-01

  There is provided a FAAH inhibitor and a prophylactic or therapeutic agent for cerebrovascular disorders or sleep disorders comprising it. The prophylactic or therapeutic agent comprises a compound of the formula (I0): wherein Z is oxygen or sulfur; R1 is aryl which may be substituted, or a heterocyclic group which may be substituted; R1a is a hydrogen atom, a hydrocarbon group which may be substituted, hydroxyl, etc.; R2 is piperidin-1,4-diyl which may be substituted, or piperazin-1,4-diyl which may be substituted; R3 is a group formed by eliminating two hydrogen atoms from a 5-membered aromatic heterocyclic group having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, which may be further substituted, -CO-, etc.; and R4 is a hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; or a salt thereof.

  本发明提供了一种 FAAH 抑制剂和一种用于脑血管疾病或睡眠障碍的预防或治疗剂。该预防或治疗剂包括式（I0）化合物： 其中 Z 是氧或硫；R1 是可被取代的芳基或可被取代的杂环基团；R1a 是氢原子、可被取代的烃基、羟基等。R2 是可被取代的哌啶-1,4-二基或可被取代的哌嗪-1,4-二基；R3 是通过从具有 1 至 3 个选自氮、氧和硫的杂原子的 5 元芳香杂环基团中消除两个氢原子而形成的基团，该基团可被进一步取代、-CO- 等；以及 R4 是可被取代的烃基或可被取代的杂环基；或其盐。