4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-cyanobenzenesulfonate

• 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: 4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-cyanobenzenesulfonate
• 英文别名: [4-[3-[1-(4-Methylsulfonylbenzoyl)piperidin-4-yl]imidazol-4-yl]phenyl] 3-cyanobenzenesulfonate；[4-[3-[1-(4-methylsulfonylbenzoyl)piperidin-4-yl]imidazol-4-yl]phenyl] 3-cyanobenzenesulfonate
• 化学式: C₂₉H₂₆N₄O₆S₂
• 分子量: 590.681
• InChiKey: LTFUTVDGOBKNTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氰基苯磺酰氯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-cyanobenzenesulfonate
  参考文献：
  名称：

  Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion

  摘要：

  The P2X7 receptor (P2X7R) has been reported as a key mediator in inflammatory processes and cancer invasion/metastasis. In this study, we report the discovery of novel P2X7R antagonists and their functional activities as potential antimetastatic agents. Modifications of the hydantoin core-skeleton and the side chain substituents of the P2X7R antagonist 7 were performed. The structure activity relationships (SAR) and optimization demonstrated the importance of the sulfonyl group at the R-1 position and the substituted position and overall size of R-2 for P2X7R antagonism. The optimized novel analogues displayed potent P2X7 receptor antagonism (IC50 = 0.11-112 nM) along with significant suppressive effects on IL-1 beta release (IC50 = 0.32-210 nM). Moreover, representative antagonists (12g, 13k, and 17d) with imidazole and uracil core skeletons significantly inhibited the invasion of MDA-MB-231 triple negative breast cancer cells and cancer cell migration in a zebrafish xenograft model, suggesting the potential therapeutic application of these novel P2X7 antagonists to block metastatic cancer.

  DOI：

  10.1021/acs.jmedchem.5b01690

文献信息

• 신규한 1-피페리디닐 이미다졸 기반 P2X7 수용체 길항제 및 이를 포함하는 암 세포 이동 및 침윤 억제용 조성물
  申请人：Gwangju Institute of Science and Technology 광주과학기술원(319980993815) BRN ▼410-82-07550

  公开号：KR20170085170A

  公开（公告）日：2017-07-24

  본 발명은 암 전이억제제로서 신규한 P2X7R 길항제 및 이들의 기능적 활성에 관한 것이다. 본 발명의 신규 화합물은 IL-1β 분비에 대해 강력한 억제효과 및 암세포의 침윤 및 이동을 억제시키는 효과를 나타내었다. 특히, 본 발명의 화합물 중 이미다졸-기반 유도체인 화합물 12g, 13k, 및 17d는 인 비트로 및 인 비보에서 강력한 길항활성을 나타내어, 새로운 암 전이억제 치료제로서의 개발을 기대할 수 있다.

  本发明涉及一种新的P2X7R拮抗剂作为抗癌转移药物以及它们的功能活性。本发明的新化合物显示出对IL-1β分泌具有强大的抑制作用，以及对癌细胞的浸润和迁移具有抑制作用。特别是，本发明的化合物中，咪唑基导向的化合物12g、13k和17d表现出在体外和体内中强大的拮抗活性，因此有望作为新的抗癌转移抑制剂进行开发。