(S)-benzyl 3-methyl-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate | 167983-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-benzyl 3-methyl-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate
• CAS: 167983-28-0
• 化学式: C₂₂H₂₅N₃O₂
• 分子量: 363.459
• InChiKey: QGUSZGZRFOOMHM-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  67.01
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-benzyl 3-methyl-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate 在 palladium on activated charcoal 氢气 作用下， 生成 (1S)-3-methyl-1-(4-phenyl-1H-imidazol-2-yl)-1-butanamine
  参考文献：
  名称：

  Design, synthesis, activity, and structure of a novel class of matrix metalloproteinase inhibitors containing a heterocyclic P2′-P3′ amide bond isostere

  摘要：

  A novel series of hydroxamate-based inhibitors of matrix metalloproteinases containing benzimidazole and imidazole heterocycles as amide bond isosteres have been prepared. Potent inhibition (in the low nanomolar range) and selectivity (> 100-fold) can be attained with inhibitors containing only one amide bond. X-ray crystal structures of matrilysin (MMP-7) with two different inhibitors bound confirm that imidazole is an excellent amide bond isostere. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00283-1
• 作为产物：
  描述：

  benzyl N-[(2S)-4-methyl-1-oxo-1-(phenacylamino)pentan-2-yl]carbamate 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 8.0h， 生成 (S)-benzyl 3-methyl-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate
  参考文献：
  名称：

  Design, synthesis, activity, and structure of a novel class of matrix metalloproteinase inhibitors containing a heterocyclic P2′-P3′ amide bond isostere

  摘要：

  A novel series of hydroxamate-based inhibitors of matrix metalloproteinases containing benzimidazole and imidazole heterocycles as amide bond isosteres have been prepared. Potent inhibition (in the low nanomolar range) and selectivity (> 100-fold) can be attained with inhibitors containing only one amide bond. X-ray crystal structures of matrilysin (MMP-7) with two different inhibitors bound confirm that imidazole is an excellent amide bond isostere. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00283-1

文献信息

• Tetrahydroimidazo[1,2‐ <i>a</i> ]pyrazine Derivatives: Synthesis and Evaluation as Gα _q ‐Protein Ligands
  作者：Jim Küppers、Tobias Benkel、Suvi Annala、Kenichi Kimura、Lisa Reinelt、Bernd K. Fleischmann、Evi Kostenis、Michael Gütschow

  DOI：10.1002/chem.202001446

  日期：2020.10

  The 5,6,7,8‐tetrahydroimidazo[1,2‐a]pyrazine derivative BIM‐46174 and its dimeric form BIM‐46187 (1) are heterocyclized dipeptides that belong to the very few cell‐permeable compounds known to preferentially silence Gαq proteins. To explore the chemical space of Gαq inhibitors of the BIM chemotype, a combinatorial approach was conducted towards a library of BIM molecules. This library was evaluated

  5,6,7,8-四氢咪唑并[1,2- a ]吡嗪衍生物 BIM-46174 及其二聚体形式 BIM-46187 ( 1 ) 是杂环化二肽，属于极少数已知优先沉默 Gα 的细胞渗透性化合物q蛋白。为了探索 BIM 化学型 Gα q抑制剂的化学空间，对 BIM 分子库进行了组合方法。该文库在基于第二信使的荧光测定中进行了评估，通过测定细胞内肌醇1-磷酸来分析 Gα q蛋白的活性。推导了结构-活性关系并获得了生物活性的结构要求，它们是（i）氧化还原反应性硫醇/二硫烷子结构，（ii）N-末端碱性氨基，（iii）环己基丙氨酸部分，和（iv）双环骨架。活性化合物表现出细胞毒性，对此原型抑制剂进行了详细研究1。该化合物以 Gα q/11独立的方式影响结构细胞骨架动力学。
• Design, Synthesis, and Evaluation of Small Molecule Gαq/11 Protein Inhibitors for the Treatment of Uveal Melanoma
  作者：Yang Ge、Shuo Shi、Jun-Jie Deng、Xue-Ping Chen、Zhendong Song、Lu Liu、Linlin Lou、Xiaolei Zhang、Xiao-Feng Xiong

  DOI：10.1021/acs.jmedchem.0c01977

  日期：2021.3.25

  uveal melanoma cells apoptosis and displayed potent antitumor activities in uveal melanoma cells viability, migration, and invasion. The effects of GQ127 on Gαq/11 signaling pathway were confirmed by analyzing the downstream effectors yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK). More importantly, GQ127 significantly suppressed UM xenograft growth in mouse model without

  葡萄膜黑色素瘤是眼部恶性肿瘤，主要由Gαq/ 11蛋白的致癌突变驱动。先前用于黑色素瘤治疗的靶向疗法仅限于特定的下游信号传导途径，很少描述了抑制“分子开关” G蛋白用于黑色素瘤治疗的方法。我们在此报告了咪唑并哌嗪衍生物作为Gαq/ 11蛋白抑制剂的发现。通过直接抑制Gαq/ 11蛋白，最有希望的化合物GQ127在肌醇单磷酸酯（IP 1）分析中显示出良好的疗效和安全性。GQ127诱导葡萄膜黑色素瘤细胞凋亡，并在葡萄膜黑色素瘤细胞的活力，迁移和侵袭中显示出强大的抗肿瘤活性。GQ127的影响通过分析下游效应物yes相关蛋白（YAP）和细胞外信号调节激酶（ERK），证实了Gαq/ 11信号通路的特异性。更重要的是，在测试剂量下，GQ127显着抑制了小鼠模型中UM异种移植的生长，而没有严重的毒性。这些发现提供了直接靶向Gαq/ 11蛋白用于葡萄膜黑色素瘤治疗的先导化合物。