N-benzyl-N,1-dimethyl-1H-imidazole-4-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-benzyl-N,1-dimethyl-1H-imidazole-4-sulfonamide
• 英文别名: N-benzyl-N,1-dimethylimidazole-4-sulfonamide
• 化学式: C₁₂H₁₅N₃O₂S
• 分子量: 265.33
• InChiKey: BWKPMBHQXBHBED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  4

文献信息

• DUAL INHIBITORS OF FARNESYLTRANSFERASE AND GERANYLGERANYLTRANSFERASE I
  申请人：H. Lee Moffitt Cancer Center and Research Institute, Inc.

  公开号：US20130190355A1

  公开（公告）日：2013-07-25

  Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC 50 value of 25 nM and a whole cell H-Ras processing IC 50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

  许多GTP酶如Ras、Ral和Rho需要经过翻酰基化或戊二烯基化的后翻译修饰，以介导恶性转化。双重翻酰基转移酶(FT)(FTI)和戊二烯基转移酶-I(GGT-1)抑制剂(GGTI)是基于乙二胺支架开发的抗癌剂。基于四倍取代乙二胺支架，这些抑制剂结构简单，易于衍生，便于进行广泛的构效关系研究。其中最有效的抑制剂表现出25 nM的体外hFTase IC50值和90 nM的整个细胞H-Ras处理IC50值。其中几种抑制剂对相关的戊二烯基转移酶酶(GGTase-I)高度选择性。一种抑制剂与磷酸戊二烯基共结晶于大鼠FTase的活性位点中的晶体结构表明，对苯二腈基团通过与Y361β残基的π-π堆积相互作用稳定，表明这些抑制剂的这个组分的重要性。
• US9040563B2
  申请人：——

  公开号：US9040563B2

  公开（公告）日：2015-05-26