methyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate | 32286-98-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate
• CAS: 32286-98-9
• 化学式: C₉H₁₂N₂O₂
• mdl: MFCD16620163
• 分子量: 180.206
• InChiKey: FCGHXNFPSZTBIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  398.3±42.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate 在 potassium carbonate 、 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 53.0h， 生成 2-(2-oxopropyl)-4,5,6,7-tetrahydro-2H-indazole-3-carboxylate
  参考文献：
  名称：

  Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth

  摘要：

  Cancer cells sustain growth by altering their metabolism to accelerated aerobic glycolysis accompanied by increased glucose demand and employ glutamine as additional nutrient source. This metabolic adaptation induces upregulation of glucose transporters GLUT-1 and -3, and simultaneous targeting of both transporters and of glutamine metabolism may offer a promising approach to inhibit cancer cell growth. We describe the discovery of the very potent glucose uptake inhibitor Glutor, which targets glucose transporters GLUT-1, -2, and -3, attenuates glycolytic flux and potently and selectively suppresses growth of a variety of cancer cell lines. Co-treatment of colon cancer cells with Glutor and glutaminase inhibitor CB-839 very potently and synergistically inhibits cancer cell growth. Such a dual inhibition promises to be particularly effective because it targets the metabolic plasticity as well as metabolic rescue mechanisms in cancer cells.

  DOI：

  10.1016/j.chembiol.2019.06.005
• 作为产物：
  描述：

  methyl 8-(diethoxyphosphoryl)-8-hydrazinylideneoct-2-ynoate 在 potassium N-iodo p-toluenesulfonamide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 2.5h， 生成 methyl 4,5,6,7-tetrahydro-1H-indazole-3-carboxylate
  参考文献：
  名称：

  重氮膦酸盐：吡唑合成中重氮烷烃的有效替代物

  摘要：

  重氮膦酸盐，很容易通过分批或流动氧化相应的腙，由 α-酮膦酸盐制备，是炔烃的 1,3-偶极环加成反应中的有用伙伴，得到N-H 吡唑，包括此类过程的第一个分子内实例。磷酰基赋予重氮 1,3-偶极子许多理想的特性。磷酰基的吸电子性质使重氮化合物稳定，使其更易于处理，而磷酰基在 [1,5]-σ 重排中容易迁移的能力使其从 C 转移到 N 以芳构化初始环加合物，因此很容易从最终的吡唑产品中去除。总体而言，重氮膦酸盐在环加成中充当稳定性差得多的重氮烷烃的替代物，其中磷酰基起着至关重要但无痕的作用。带有吸电子基团的炔烃更容易进行环加成反应，并且对不对称炔烃具有区域专一性。

  DOI：

  10.1002/chem.202101788

文献信息

• Highly Regioselective Organocatalyzed Synthesis of Pyrazoles from Diazoacetates and Carbonyl Compounds
  作者：Lei Wang、Jiayao Huang、Xiaojie Gong、Jian Wang

  DOI：10.1002/chem.201300047

  日期：2013.6.3

  β‐ketoesters, β‐diketones, and aldehydes), as well as the operational simplicity of this process, a convenient, practical, and highly modular pyrazole synthesis has been developed. We believe that this work will arouse more research interest in the organocatalytic synthesis of other biologically active heterocycles. Such studies are currently underway in our laboratory.

  已经开发了一系列羰基化合物与重氮乙酸酯之间的一般有机催化逆电子需求[3 + 2]环加成反应。该反应被仲胺作为“绿色促进剂”催化，以生成具有高区域选择性的取代吡唑。值得注意的是，这种[3 + 2]环加成反应在室温下使用简单且廉价的催化剂即可有效地进行。考虑到起始原料（例如酮，β-酮酸酯，β-二酮和醛）的多样性和现成的可用性，以及该方法的操作简便性，已开发了一种方便，实用且高度模块化的吡唑合成方法。我们相信这项工作将在其他生物活性杂环的有机催化合成中引起更多的研究兴趣。
• HETEROCYCLIC COMPOUND
  申请人：Mochizuki Michiyo

  公开号：US20110118236A1

  公开（公告）日：2011-05-19

  An object of the present invention is to provide a novel AMPA receptor potentiator. A compound represented by the following formula (I) or a salt thereof: wherein in formula (I) R 1 represents (1) a halogen atom, or (2) cyano group, or the like; Ra and Rb each independently represent a hydrogen atom or C 1-4 alkyl; L represents a bond, or a spacer in which the number of atoms in the main chain is 1 to 8; Ring A represents (1) a non-aromatic carbon ring of 4-8 carbon atoms, or (2) a 4- to 8-membered non-aromatic heterocycle either of which is optionally substituted with 1 or more substituents selected from (a) halogen atoms, and (b) cyano group; and Ar represents a substituted phenyl group, or optionally substituted 5- or 6-membered aromatic heterocyclic group.

  本发明的目的是提供一种新型AMPA受体增强剂。化合物由以下式(I)或其盐所表示：其中在式(I)中，R1表示（1）卤素原子或（2）氰基等；Ra和Rb各自独立地表示氢原子或C1-4烷基；L表示键或主链中原子数为1至8的间隔物；环A表示（1）4-8个碳原子的非芳香碳环，或（2）4-至8个成员的非芳香杂环，其中任一环均可以选择性地用1个或多个取代基所取代，所述取代基选择自(a)卤素原子和(b)氰基；Ar表示取代苯基或可选择性取代的5-或6-成员芳香杂环基。
• ALKYNYL ALCOHOLS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20150065482A1

  公开（公告）日：2015-03-05

  The invention relates to compounds of Formula (0): wherein Q, A 1 -A 8 , R 4 and R 5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

  本发明涉及化合物公式（0）：其中Q，A1-A8，R4和R5的含义如本文所述。公式（0）的化合物及其制药组合物在治疗观察到NF-kB信号不良或过度激活的疾病和疾病中非常有用。
• An Overlooked Pathway in 1,3‐Dipolar Cycloadditions of Diazoalkanes with Enamines
  作者：Le Li、Peter Mayer、David S. Stephenson、Armin R. Ofial、Robert J. Mayer、Herbert Mayr

  DOI：10.1002/anie.202117047

  日期：2022.3.14

  The most popular illustration of the role of Frontier Molecular Orbitals (FMO) in 1,3-dipolar cycloadditions must be revised: the reactions of diazoacetates with enamines proceed stepwise and are controlled by interactions of the enamines’ HOMO with π*N=N (LUMO) and not with the unoccupied orbital of the heteropropargyl fragment (LUMO+1). Tautomers of the intermediate zwitterions have been observed

  前沿分子轨道 (FMO) 在 1,3-偶极环加成中的作用的最流行的说明必须修改：重氮乙酸酯与烯胺的反应逐步进行，并由烯胺的 HOMO 与 π* N=N的相互作用控制（ LUMO)，而不是杂炔基片段的未占据轨道 (LUMO+1)。中间两性离子的互变异构体已经被观察到，并通过 DFT 计算研究了其机制。
• Quantification of the Electrophilicities of Diazoalkanes: Kinetics and Mechanism of Azo Couplings with Enamines and Sulfonium Ylides
  作者：Le Li、Robert J. Mayer、David S. Stephenson、Peter Mayer、Armin R. Ofial、Herbert Mayr

  DOI：10.1002/chem.202201376

  日期：2022.10.4

  Enamines and sulfonium ylides attack the terminal nitrogen of diazoalkanes with rate-determining formation of zwitterions. The measured second-order rate constants were used to determine the one-bond electrophilicities E of the diazoalkanes. Pyrazolines obtained from the reactions of diazoalkanes with enamines are not formed by 1,3-dipolar cycloadditions, but by cyclization of hydrazonoenamines initially

  烯胺和硫叶立德攻击重氮烷烃的末端氮，并决定两性离子的形成。测得的二阶速率常数用于确定重氮烷烃的单键亲电性E。从重氮烷烃与烯胺的反应中获得的吡唑啉不是通过 1,3-偶极环加成反应形成的，而是通过最初由中间两性离子中的质子移动形成的亚肼基胺环化形成的。