2-[Methyl-(4-methyl-pent-3-enyl)-amino]-ethyl-diphosphate

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 英文名称: 2-[Methyl-(4-methyl-pent-3-enyl)-amino]-ethyl-diphosphate
• 英文别名: 2-[methyl(4-methylpent-3-enyl)amino]ethyl phosphono hydrogen phosphate
• 化学式: C₉H₂₁NO₇P₂
• 分子量: 317.216
• InChiKey: UWHNDWYDKGVRGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-氯-3-甲基-2-丁烯 在 lithium aluminium tetrahydride 、 tris(tetra-n-butylammonium) hydrogen pyrophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 生成 2-[Methyl-(4-methyl-pent-3-enyl)-amino]-ethyl-diphosphate
  参考文献：
  名称：

  Inhibition of Geranylgeranyl Diphosphate Synthase by Bisphosphonates and Diphosphates:  A Potential Route to New Bone Antiresorption and Antiparasitic Agents

  摘要：

  We report the inhibition of a human recombinant geranylgeranyl diphosphate synthase (GGPPSase) by 23 bisphosphonates and six azaprenyl diphosphates. The IC50 values range from 140 nM to 690,muM. None of the nitrogen-containing bisphosphonates that inhibit farnesyl diphosphate synthase were effective in inhibiting the GGPPSase enzyme. Using three-dimensional quantitative structure-activity relationship/comparative molecular field analysis (CoMFA) methods, we find a good correlation between experimental and predicted activity: R-2 = 0.938, R-cv(2) = 0.900, R-bs(2) = 0.938, and F-test = 86.8. To test the predictive utility of the CoMFA approach, we used three training sets of 25 compounds each to generate models to predict three test sets of three compounds. The rms pIC(50) error for the nine predictions was 0.39. We also investigated the pharmacophore of these GGPPSase inhibitors using the Catalyst method. The results demonstrated that Catalyst predicted the pIC(50) values for the nine test set compounds with an rms error of 0.28 (R-2 between experimental and predicted activity of 0.948).

  DOI：

  10.1021/jm010412y

文献信息

• Inhibition of Geranylgeranyl Diphosphate Synthase by Bisphosphonates and Diphosphates:  A Potential Route to New Bone Antiresorption and Antiparasitic Agents
  作者：Christina M. Szabo、Yoshihiro Matsumura、Sayaka Fukura、Michael B. Martin、John M. Sanders、Suraj Sengupta、John A. Cieslak、Timothy C. Loftus、Christopher R. Lea、Hyung-Jae Lee、Ali Koohang、Robert M. Coates、Hiroshi Sagami、Eric Oldfield

  DOI：10.1021/jm010412y

  日期：2002.5.1

  We report the inhibition of a human recombinant geranylgeranyl diphosphate synthase (GGPPSase) by 23 bisphosphonates and six azaprenyl diphosphates. The IC50 values range from 140 nM to 690,muM. None of the nitrogen-containing bisphosphonates that inhibit farnesyl diphosphate synthase were effective in inhibiting the GGPPSase enzyme. Using three-dimensional quantitative structure-activity relationship/comparative molecular field analysis (CoMFA) methods, we find a good correlation between experimental and predicted activity: R-2 = 0.938, R-cv(2) = 0.900, R-bs(2) = 0.938, and F-test = 86.8. To test the predictive utility of the CoMFA approach, we used three training sets of 25 compounds each to generate models to predict three test sets of three compounds. The rms pIC(50) error for the nine predictions was 0.39. We also investigated the pharmacophore of these GGPPSase inhibitors using the Catalyst method. The results demonstrated that Catalyst predicted the pIC(50) values for the nine test set compounds with an rms error of 0.28 (R-2 between experimental and predicted activity of 0.948).