ethyl 1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carbohydrazide | 1381840-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carbohydrazide
• 英文别名: 1H,4H,5H,6H,7H,8H-Cyclohepta[c]pyrazole-3-carbohydrazide；1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carbohydrazide
• CAS: 1381840-58-9
• 化学式: C₉H₁₄N₄O
• 分子量: 194.236
• InChiKey: OJJORXVLEKXUPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carbohydrazide 、 2-氯苯甲醛 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Suprafenacine, an Indazole-Hydrazide Agent, Targets Cancer Cells Through Microtubule Destabilization

  摘要：

  微管是抗癌疗法中经过充分验证的目标。然而，微管结合剂（TBA）的临床开发一直受到毒性和化疗抗性问题的阻碍，因此有必要寻找新的TBA。在此，我们报告了一种新型细胞通透性、微管不稳定性分子的鉴定——4,5,6,7-四氢-1H-吲唑-3-羧酸[1-甲苯基-甲-(E)-亚基]-酰肼（命名为Suprafenacine，SRF）。SRF是通过对注释化学库的计算机筛选鉴定的，它被证明在秋水仙素结合位点与微管结合并抑制聚合。这导致G2/M细胞周期阻滞和通过线粒体介导的凋亡途径的细胞死亡。细胞死亡之前是线粒体膜电位的丧失，JNK介导的Bcl-2和Bad的磷酸化，以及caspase-3的激活。有趣的是，SRF被发现能选择性抑制癌细胞增殖，并通过其绕过多药耐药转运蛋白P-糖蛋白的能力对耐药癌细胞有效。总的来说，我们的结果表明SRF具有作为抗癌化疗药物的潜力，并为开发改进的抗癌药物提供了另一种支架结构。

  DOI：

  10.1371/journal.pone.0110955
• 作为产物：
  描述：

  ethyl α,2-dioxocycloheptaneacetate 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 36.0h， 生成 ethyl 1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carbohydrazide
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors

  摘要：

  Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP‐4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP‐4 inhibitors, featuring the pyrazole‐3‐carbohydrazone scaffold, have been discovered using an integrated approach of structure‐based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low‐to‐mid‐micromolar inhibitory level compounds (1–5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k–l, and 7a–e) were found to show inhibitory effects against DPP‐4. Molecular docking models give rational explanation about structure–activity relationships. Based on eight DPP‐4 inhibitors (1–5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP‐4 inhibitors design.

  DOI：

  10.1111/j.1747-0285.2012.01365.x