tetraisopropyl 1-fluoro-2-(3-pyridinyl)ethylidene-1,1-bisphosphonate | 960592-80-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: tetraisopropyl 1-fluoro-2-(3-pyridinyl)ethylidene-1,1-bisphosphonate
• 英文别名: 3-[2,2-Bis[di(propan-2-yloxy)phosphoryl]-2-fluoroethyl]pyridine
• CAS: 960592-80-7
• 化学式: C₁₉H₃₄FNO₆P₂
• 分子量: 453.428
• InChiKey: RWQVWRGHPMFVLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetraisopropyl 1-fluoro-2-(3-pyridinyl)ethylidene-1,1-bisphosphonate 在 盐酸 作用下， 以94%的产率得到1-fluoro-2-(3-pyridyl)ethylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of α-Halogenated Bisphosphonate and Phosphonocarboxylate Analogues of Risedronate

  摘要：

  alpha-Halogenated. analogues of the anti-resorptive bisphosphonate risedronate (5, Ris) and its phosphonocarboxylate cognate (7, 3-PEHPC were synthesized and compared with 5, 7, and the corresponding desoxy analogues in bone mineral affinity and mevalonate pathway inhibition assays. The Ris (5e-h) and 3-PEHPC (7e-h) analogues had decreased bone mineral affinity, confirming that the alpha-OH group in 5 and 7 enhances bone affinity. The 5 alpha-halo-analogues potently inhibited farnesyl pyrophosphate synthase (FPPS) with IC50 values from 16 ((alpha-F) to 340 (alpha-Br) nM (5, 6 nM). In contrast, 7 alpha-halo-analogues were ineffective versus FPPS (IC50 > 600 mu M), but inhibited Rab geranylgeranyl transferase (RGGT) IC50 = 16-35 mu M) similarly to 7 itself (IC50 = 24 mu M). The alpha-F analogue 7e was 1-2 times as active as 7 in J774 cell viability and Rab11 prenylation inhibition assays.

  DOI：

  10.1021/jm0702884
• 作为产物：
  描述：

  tetraisopropyl 2-(3-pyridinyl)ethylidene-1,1-bisphosphonate 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以66%的产率得到tetraisopropyl 1-fluoro-2-(3-pyridinyl)ethylidene-1,1-bisphosphonate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of α-Halogenated Bisphosphonate and Phosphonocarboxylate Analogues of Risedronate

  摘要：

  alpha-Halogenated. analogues of the anti-resorptive bisphosphonate risedronate (5, Ris) and its phosphonocarboxylate cognate (7, 3-PEHPC were synthesized and compared with 5, 7, and the corresponding desoxy analogues in bone mineral affinity and mevalonate pathway inhibition assays. The Ris (5e-h) and 3-PEHPC (7e-h) analogues had decreased bone mineral affinity, confirming that the alpha-OH group in 5 and 7 enhances bone affinity. The 5 alpha-halo-analogues potently inhibited farnesyl pyrophosphate synthase (FPPS) with IC50 values from 16 ((alpha-F) to 340 (alpha-Br) nM (5, 6 nM). In contrast, 7 alpha-halo-analogues were ineffective versus FPPS (IC50 > 600 mu M), but inhibited Rab geranylgeranyl transferase (RGGT) IC50 = 16-35 mu M) similarly to 7 itself (IC50 = 24 mu M). The alpha-F analogue 7e was 1-2 times as active as 7 in J774 cell viability and Rab11 prenylation inhibition assays.

  DOI：

  10.1021/jm0702884

文献信息

• Synthesis and Biological Evaluation of α-Halogenated Bisphosphonate and Phosphonocarboxylate Analogues of Risedronate
  作者：Mong S. Marma、Zhidao Xia、Charlotte Stewart、Fraser Coxon、James E. Dunford、Rudi Baron、Boris A. Kashemirov、Frank H. Ebetino、James T. Triffitt、R. Graham G. Russell、Charles E. McKenna

  DOI：10.1021/jm0702884

  日期：2007.11.1

  alpha-Halogenated. analogues of the anti-resorptive bisphosphonate risedronate (5, Ris) and its phosphonocarboxylate cognate (7, 3-PEHPC were synthesized and compared with 5, 7, and the corresponding desoxy analogues in bone mineral affinity and mevalonate pathway inhibition assays. The Ris (5e-h) and 3-PEHPC (7e-h) analogues had decreased bone mineral affinity, confirming that the alpha-OH group in 5 and 7 enhances bone affinity. The 5 alpha-halo-analogues potently inhibited farnesyl pyrophosphate synthase (FPPS) with IC50 values from 16 ((alpha-F) to 340 (alpha-Br) nM (5, 6 nM). In contrast, 7 alpha-halo-analogues were ineffective versus FPPS (IC50 > 600 mu M), but inhibited Rab geranylgeranyl transferase (RGGT) IC50 = 16-35 mu M) similarly to 7 itself (IC50 = 24 mu M). The alpha-F analogue 7e was 1-2 times as active as 7 in J774 cell viability and Rab11 prenylation inhibition assays.