triethyl 2-chloro-3-(3-pyridinyl)-2-phosphonopropionate | 960592-87-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: triethyl 2-chloro-3-(3-pyridinyl)-2-phosphonopropionate
• 英文别名: Ethyl 2-chloro-2-diethoxyphosphoryl-3-pyridin-3-ylpropanoate
• CAS: 960592-87-4
• 化学式: C₁₄H₂₁ClNO₅P
• 分子量: 349.751
• InChiKey: KDRMVEMPIHOLBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  triethyl 2-chloro-3-(3-pyridinyl)-2-phosphonopropionate 在 盐酸 作用下， 以69.1%的产率得到2-Chloro-3-(3-pyridinyl)-2-phosphonopropionic 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：

  triethyl 3-(3-pyridinyl)-2-phosphonopropionate 在 sodium hydride 、 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.83h， 以93%的产率得到triethyl 2-chloro-3-(3-pyridinyl)-2-phosphonopropionate
  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.