FTI-2733 | 1247018-44-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: FTI-2733
• 英文别名: N-(2-((2-cyanopyridin-5-yl)((1-methyl-1H-imidazol-5-yl)methyl)-amino)ethyl)-1-methyl-N-((1-(pyrimidin-2-yl)piperidin-4-yl)methyl)-1H-imidazole-4-sulfonamide；N-[2-[(6-cyanopyridin-3-yl)-[(3-methylimidazol-4-yl)methyl]amino]ethyl]-1-methyl-N-[(1-pyrimidin-2-ylpiperidin-4-yl)methyl]imidazole-4-sulfonamide
• CAS: 1247018-44-5
• 化学式: C₂₇H₃₃N₁₁O₂S
• 分子量: 575.698
• InChiKey: VJMJXVYTFCZQCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  N-(2-((2-cyanopyridin-5-yl)amino)ethyl)-1-methyl-N-((1-(pyrimidin-2-yl)piperidin-4-yl)methyl)-1H-imidazole-4-sulfonamide 、 5-(氯甲基)-1-甲基咪唑盐酸盐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以78%的产率得到FTI-2733
  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

文献信息

• [EN] DUAL INHIBITORS OF FARNESYLTRANSFERASE AND GERANYLGERANYLTRANSFERASE I<br/>[FR] INHIBITEURS DOUBLES DE FARNÉSYLTRANSFÉRASE ET DE GÉRANYLGÉRANYLTRANSFÉRASE 1
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2012034038A2

  公开（公告）日：2012-03-15

  Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-l (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 IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-l (GGTase-l). 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 Y361 β residue, suggesting an importance of this component of the inhibitors.