[N-(2-aminoethyl)-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide | 1247018-10-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: [N-(2-aminoethyl)-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide
• 英文别名: N-(2-aminoethyl)-1-methyl-N-[(1-pyrimidin-2-ylpiperidin-4-yl)methyl]imidazole-4-sulfonamide
• CAS: 1247018-10-5
• 化学式: C₁₆H₂₅N₇O₂S
• 分子量: 379.486
• InChiKey: QFHHYZGRSOGKMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [N-(2-aminoethyl)-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide 、 3,4,5-三氟苯腈 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以97%的产率得到[N-{2-(2,6-difluoro-4-cyanophenyl)-aminoethyl}-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Potent, Ethylenediamine-Based, Mammalian Farnesyltransferase Inhibitors as Anticancer Agents

  摘要：

  A potent class of anticancer. human farnesyltransferase (111:Tase) inhibitors has been identified by "piggy-backing" on potent, antimalarial inhibitors of Plosmodium falciparum farnesyltransferase (P/FTase). On the basis of a 4-Fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating the extensive structure activity relationship (SA R) study reported herein. Our most potent inhibitor is compound If, which exhibited an in vitro hFTase IC50 value of 25 nm and a whole cell H-Ras processing IC50 value of 90 nM. Moreover, it is noteworthy that several of our inhibitors proved highly selective For hFTase (up to 333-fold) over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-l). A crystal structure of inhibitor la co-crystallized with farnesyl pyrophosphate (FPP) in the active site of rat FTase illustrates that the para-benzonitrile moiety of la is stabilized by pi-pi stacking interaction with the Y361 beta residue, suggesting a structural explanation for the observed importance of this component of our inhibitors.

  DOI：

  10.1021/jm1001748
• 作为产物：
  描述：

  [N-(2-tert-butoxycarbonylaminoethyl)-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到[N-(2-aminoethyl)-N-{N-(2-pyrimidinyl)-piperidin-4-ylmethyl}]-1-methyl-1H-imidazole-4-sulfonamide
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Potent, Ethylenediamine-Based, Mammalian Farnesyltransferase Inhibitors as Anticancer Agents

  摘要：

  A potent class of anticancer. human farnesyltransferase (111:Tase) inhibitors has been identified by "piggy-backing" on potent, antimalarial inhibitors of Plosmodium falciparum farnesyltransferase (P/FTase). On the basis of a 4-Fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating the extensive structure activity relationship (SA R) study reported herein. Our most potent inhibitor is compound If, which exhibited an in vitro hFTase IC50 value of 25 nm and a whole cell H-Ras processing IC50 value of 90 nM. Moreover, it is noteworthy that several of our inhibitors proved highly selective For hFTase (up to 333-fold) over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-l). A crystal structure of inhibitor la co-crystallized with farnesyl pyrophosphate (FPP) in the active site of rat FTase illustrates that the para-benzonitrile moiety of la is stabilized by pi-pi stacking interaction with the Y361 beta residue, suggesting a structural explanation for the observed importance of this component of our inhibitors.

  DOI：

  10.1021/jm1001748