恩前列素中间体 | 51638-93-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 恩前列素中间体
• 英文名称: (3aR,4R,5R,6aS)-5-Hydroxy-4-((E)-(R)-3-hydroxy-4-phenoxy-but-1-enyl)-hexahydro-cyclopenta[b]furan-2-one
• 英文别名: 2H-Cyclopenta[b]furan-2-one,hexahydro-5-hydroxy-4-[(1E,3R)-3-hydroxy-4-phenoxy-1-buten-1-yl]-,(3aR,4R,5R,6aS)-；(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one
• CAS: 51638-93-8
• 化学式: C₁₇H₂₀O₅
• 分子量: 304.343
• InChiKey: JWVCXPNASRWURX-QARSFKSDSA-N

物化性质

• 沸点：
  520.1±50.0 °C(Predicted)
• 密度：
  1.345±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  恩前列素中间体 在 jones reagent 、 sodium methylsulfinylcarbanide 、 二异丁基氢化铝 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 正己烷 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 16.91h， 生成 硫前列酮
  参考文献：
  名称：

  N-(Methanesulfonyl)-16-phenoxyprostaglandin carboxamides: tissue-selective, uterine stimulants

  摘要：

  In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).

  DOI：

  10.1021/jm00143a018
• 作为产物：
  描述：

  苯氧乙酸甲酯 在 sodium hydride 、 三乙基硼氢化锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 恩前列素中间体
  参考文献：
  名称：

  N-(Methanesulfonyl)-16-phenoxyprostaglandin carboxamides: tissue-selective, uterine stimulants

  摘要：

  In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).

  DOI：

  10.1021/jm00143a018

文献信息

• PROCESSES AND INTERMEDIATES FOR THE PREPARATIONS OF ISOMER FREE PROSTAGLANDINS
  申请人：CHIROGATE INTERNATIONAL INC.

  公开号：US20150051410A1

  公开（公告）日：2015-02-19

  Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: wherein R 2 , R 3 and R 4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

  提供了一种用于制备基本上不含5,6-顺式异构体的化合物I-2的新工艺：其中R2、R3和R4如规范中定义。还提供了用于制备无异构体前列腺素及其衍生物的新中间体。
• Synthesis and Biological Evaluation of Prostaglandin-F Alkylphosphinic Acid Derivatives as Bone Anabolic Agents for the Treatment of Osteoporosis
  作者：David L. Soper、Jared B. J. Milbank、Glen E. Mieling、Michelle J. Dirr、Andrew S. Kende、Robin Cooper、Webster S. S. Jee、Wei Yao、Jian Liang Chen、Mark Bodman、Mark W. Lundy、Biswanath De、Mark E. Stella、Frank H. Ebetino、Yili Wang、Mitchell A. deLong、John A. Wos

  DOI：10.1021/jm010264b

  日期：2001.11.1

  parent carboxylic acid. When evaluated in vivo, the methyl phosphinic acid analogue (4b) produced a bone anabolic response in rats, returning bone mineral volume (BMV) [corrected], to intact levels in the distal femur in the ovariectomized rat (OVX) model. These results suggest that prostaglandins of this class may be useful agents in the treatment of diseases associated with bone loss.

  前列腺素-F家族的一系列新型C（1）烷基次膦酸类似物已在八个人类前列腺素受体上进行了评估，可用于治疗骨质疏松症。使用分子建模作为基于结构的药物设计的工具，我们发现次膦酸部分（P（O）（OH）R）在人前列腺素FP结合测定中表现为C（1）羧酸的等排体与母体羧酸相比，在体外具有增强的hFP受体选择性。当在体内进行评估时，甲基次膦酸类似物（4b）在大鼠中产生了骨合成代谢反应，在去卵巢大鼠（OVX）模型中，股骨远端的完整骨矿物质体积（BMV）[校正]返回完整的水平。
• COOPER, GARY F.;WREN, L.;VAN, HORN ALBERT R.;LI, TSUNG-TEE;BENRD, COIIN C+
  作者：COOPER, GARY F.、WREN, L.、VAN, HORN ALBERT R.、LI, TSUNG-TEE、BENRD, COIIN C+

  DOI：——

  日期：——
• COOPER, GARY E.;FRIED, JOHN H.;WATERBURY, L. DAVID
  作者：COOPER, GARY E.、FRIED, JOHN H.、WATERBURY, L. DAVID

  DOI：——

  日期：——
• TOLSTIKOV, G. A.;ADLER, M. EH.;MIFTAXOV, M. S., ZH. ORGAN. XIMII, 25,(1989) N0, S. 2113-2119
  作者：TOLSTIKOV, G. A.、ADLER, M. EH.、MIFTAXOV, M. S.

  DOI：——

  日期：——