6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-one | 1346155-48-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-one
• 英文别名: 6,6-dimethyl-5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one；6,6-Dimethyl-5H-pyrrolo[1,2-C]imidazol-7(6H)-one
• CAS: 1346155-48-3
• 化学式: C₈H₁₀N₂O
• 分子量: 150.18
• InChiKey: BPEXJBLMFWNMJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-one 在 N-碘代丁二酰亚胺 、 一水合肼 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1,3-diiodo-6,6-dimethyl-5,7-dihydropyrrolo[1,2-c]imidazole
  参考文献：
  名称：

  [EN] NEW COMPOUNDS AND METHODS
  [FR] NOUVEAUX COMPOSÉS ET PROCÉDÉS

  摘要：

  本发明涉及式(I)的化合物或其药用可接受的盐、溶剂化合物、水合物、互变异构体、光学异构体、N-氧化物和/或前药。本发明还涉及包括本发明化合物的药物组合物，以及它们在治疗或预防抑制c-ABL有益的医疗状况中的使用。

  公开号：

  WO2020260871A1
• 作为产物：
  描述：

  5H-吡咯并[1,2-c]咪唑-7(6H)-酮 、 碘甲烷 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 以43%的产率得到6,6-dimethyl-5H-pyrrolo[1,2-c]imidazol-7-one
  参考文献：
  名称：

  1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4

  摘要：

  A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50) = 54 nM) and antitubulin activity (HCT-116 IC(50) = 34 nM and tubulin polymerization IC(50) similar to 1 mu M). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.068

文献信息

• [EN] NEW COMPOUNDS AND METHODS<br/>[FR] NOUVEAUX COMPOSÉS ET PROCÉDÉS
  申请人：BENEVOLENTAI BIO LTD

  公开号：WO2020260871A1

  公开（公告）日：2020-12-30

  The present invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, optical isomer, N-oxide, and/or prodrug thereof. The present invention also relates to pharmaceutical compositions comprising the compounds of the invention, and to their use in the treatment or prevention of medical conditions in which inhibition of c-ABL is beneficial. (I)

  本发明涉及式(I)的化合物或其药用可接受的盐、溶剂化合物、水合物、互变异构体、光学异构体、N-氧化物和/或前药。本发明还涉及包括本发明化合物的药物组合物，以及它们在治疗或预防抑制c-ABL有益的医疗状况中的使用。
• 1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4
  作者：Alexander L. Ruchelman、Hon-Wah Man、Roger Chen、Wei Liu、Ling Lu、Dorota Cedzik、Ling Zhang、Jim Leisten、Alice Collette、Rama Krishna Narla、Heather K. Raymon、George W. Muller

  DOI：10.1016/j.bmc.2011.08.068

  日期：2011.11

  A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50) = 54 nM) and antitubulin activity (HCT-116 IC(50) = 34 nM and tubulin polymerization IC(50) similar to 1 mu M). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd. (C) 2011 Elsevier Ltd. All rights reserved.