tetraisopropyl 2-(3,5-bis(acetylthioethyl)phenyl)ethane-1,1-diphosphonate | 241472-23-1

• 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 2-(3,5-bis(acetylthioethyl)phenyl)ethane-1,1-diphosphonate
• 英文别名: Tetraisopropyl 2-(3,5-bis(acetylthiomethyl)phenyl)ethane-1,1-diphosphonate；S-[[3-(acetylsulfanylmethyl)-5-[2,2-bis[di(propan-2-yloxy)phosphoryl]ethyl]phenyl]methyl] ethanethioate
• CAS: 241472-23-1
• 化学式: C₂₆H₄₄O₈P₂S₂
• 分子量: 610.71
• InChiKey: RCZYWSVLGRQJOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  38
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tetraisopropyl 2-(3,5-bis(acetylthioethyl)phenyl)ethane-1,1-diphosphonate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Prostaglandin E2-bisphosphonate conjugates: potential agents for treatment of osteoporosis

  摘要：

  Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E-2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE(2). The conjugate 3, an amide at C-1 of PGE(2) proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE(2), C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE(2) at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE(2). (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00045-0
• 作为产物：
  描述：

  1,3,5-三(溴甲基)苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 生成 tetraisopropyl 2-(3,5-bis(acetylthioethyl)phenyl)ethane-1,1-diphosphonate
  参考文献：
  名称：

  Prostaglandin E2-bisphosphonate conjugates: potential agents for treatment of osteoporosis

  摘要：

  Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E-2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE(2). The conjugate 3, an amide at C-1 of PGE(2) proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE(2), C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE(2) at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE(2). (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00045-0

文献信息

• Prostaglandin conjugates for treating or preventing bone disease
  申请人：Merck Frosst Canada & Co.

  公开号：US06121253A1

  公开（公告）日：2000-09-19

  This invention relates to prostaglandin-bisphosphonate conjugates. These conjugates are effective for treating or preventing bone diseases such as osteoporosis. These conjugates simultaneously deliver a prostaglandin agent for increasing bone formation and a bisphosphonate agent for inhibiting bone resorption.

  本发明涉及前列腺素-双磷酸盐偶联物。这些偶联物对于治疗或预防骨质疏松等骨病具有有效性。这些偶联物同时传递前列腺素药物以增加骨形成和双磷酸盐药物以抑制骨吸收。
• Prostaglandin E2-bisphosphonate conjugates: potential agents for treatment of osteoporosis
  作者：Laurent Gil、Yongxin Han、Evan E. Opas、Gideon A. Rodan、Réjean Ruel、J.Gregory Seedor、Peter C. Tyler、Robert N. Young

  DOI：10.1016/s0968-0896(99)00045-0

  日期：1999.5

  Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E-2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE(2). The conjugate 3, an amide at C-1 of PGE(2) proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE(2), C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE(2) at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE(2). (C) 1999 Elsevier Science Ltd. All rights reserved.