acetic acid (4-cyano-phenyl)-(1-trityl-1H-imidazol-4-yl)methyl ester | 198205-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: acetic acid (4-cyano-phenyl)-(1-trityl-1H-imidazol-4-yl)methyl ester
• 英文别名: acetic acid (4-cyano-phenyl)-(1-trityl-1H-imidazol-4-yl)-methyl ester；(4-Cyanophenyl)(1-trityl-1H-imidazol-4-yl)methyl acetate；[(4-cyanophenyl)-(1-tritylimidazol-4-yl)methyl] acetate
• CAS: 198205-94-6
• 化学式: C₃₂H₂₅N₃O₂
• 分子量: 483.569
• InChiKey: QBMCKEHQSJKDSE-UHFFFAOYSA-N

物化性质

• 沸点：
  638.1±55.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  acetic acid (4-cyano-phenyl)-(1-trityl-1H-imidazol-4-yl)methyl ester 在 5% Pd/C 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 以78%的产率得到4-(1-trityl-1H-imidazol-4-ylmethyl)-benzonitrile
  参考文献：
  名称：

  4-Benzyl-1H-imidazoles with Oxazoline Termini as Histamine H₃ Receptor Agonists

  摘要：

  Research on the therapeutic applications of the histamine H-3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R acyonists have received less attention despite their potential use in several disease areas. The lower availability of H3R agonists not only hampers their full therapeutic exploration, it also prevents an unequivocal understanding of the structural requirements for H3R activation. In the light of these important issues, we present our findings on 4-benzyl-1H-imidazole-based H3R agonists. Starting from two high throughput screen hits (10 and 11), the benzyl side chain was altered with lipophilic groups using combinatorial and classical chemical approaches (compounds 12-31). Alkyne- or oxazolino-substituents gave excellent affinities and agonist activities up to the single digit nM range. Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research.

  DOI：

  10.1021/jm7014149
• 作为产物：
  描述：

  4-[hydroxy-(1-trityl-1H-imidazol-4-yl)methyl]benzonitrile 在 乙酸酐 、 碳酸氢钠 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 acetic acid (4-cyano-phenyl)-(1-trityl-1H-imidazol-4-yl)methyl ester
  参考文献：
  名称：

  Inhibitors of farnesyl-protein transferase

  摘要：

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras法尼酰化的化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制法尼基-蛋白转移酶和致癌基因蛋白Ras法尼酰化的方法。

  公开号：

  US05939439A1

文献信息

• Design, synthesis, and activity of achiral analogs of 2-quinolones and indoles as non-thiol farnesyltransferase inhibitors
  作者：Qun Li、Keith W. Woods、Weibo Wang、Nan-Horng Lin、Akiyo Claiborne、Wen-zhen Gu、Jerry Cohen、Vincent S. Stoll、Charles Hutchins、David Frost、Saul H. Rosenberg、Hing L. Sham

  DOI：10.1016/j.bmcl.2005.02.062

  日期：2005.4

  Beginning with the structure of tipifarnib (1), a series of inhibitors of FTase have been synthesized by transposition of the D-ring to the imidazole and subsequent modification of the 2-quinolone motif. The compounds in the new series may be achiral and have structural features that allow for analogs that are difficult or impossible to make in the tertiary carbon-based tipifarnib series. The most

  从替非法尼（1）的结构开始，已通过将D环转位至咪唑并随后修饰了2-喹诺酮基序，合成了一系列FTase抑制剂。新系列中的化合物可能是非手性的，其结构特征使得难以或不可能在基于叔碳的替非法尼系列中制备类似物。最有效的化合物（4d）在体外对FTase的活性是Tipifarnib的4倍。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP0951285A1

  公开（公告）日：1999-10-27
• US5939439A
  申请人：——

  公开号：US5939439A

  公开（公告）日：1999-08-17
• US6077853A
  申请人：——

  公开号：US6077853A

  公开（公告）日：2000-06-20
• [EN] INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] INHIBITEURS DE FARNESYL-PROTEINE TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：WO1998029119A1

  公开（公告）日：1998-07-09

  (EN) The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.(FR) La présente invention concerne des composés qui inhibent la farnésyl-protéine transférase (FTase). L'invention concerne également la farnésylation de la protéine oncogène Ras. L'invention concerne enfin des compositions chimiothérapiques qui renferment les composés de la présente invention, les procédés permettant d'inhiber la farnésyl-protéine transférase, et la farnésylation de la protéine oncogène Ras