21-(methanesulphonyloxy)-16α-methylpregna-1,4,9(11)-trien-3,20-dione | 197711-91-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 21-(methanesulphonyloxy)-16α-methylpregna-1,4,9(11)-trien-3,20-dione
• 英文别名: [2-oxo-2-[(8S,10S,13S,14S,16R,17S)-10,13,16-trimethyl-3-oxo-6,7,8,12,14,15,16,17-octahydrocyclopenta[a]phenanthren-17-yl]ethyl] methanesulfonate
• CAS: 197711-91-4
• 化学式: C₂₃H₃₀O₅S
• 分子量: 418.554
• InChiKey: XWWYKFZYEZHAEA-OYLUHIHXSA-N

物化性质

• 沸点：
  599.2±50.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  85.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(1-哌嗪)-2,6-双-(1-吡咯烷)-嘧啶 、 21-(methanesulphonyloxy)-16α-methylpregna-1,4,9(11)-trien-3,20-dione 在 potassium carbonate 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 42.0h， 生成 替拉扎特
  参考文献：
  名称：

  Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma

  摘要：

  A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.

  DOI：

  10.1021/jm00166a010
• 作为产物：
  描述：

  16α-methyl-21-hydroxypregna-1,4,9(11)-triene-3,20-dione 、 甲基磺酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 21-(methanesulphonyloxy)-16α-methylpregna-1,4,9(11)-trien-3,20-dione
  参考文献：
  名称：

  Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma

  摘要：

  A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.

  DOI：

  10.1021/jm00166a010

文献信息

• Steroids, their use as medicaments, their preparation process, the intermediates of this process and the compositions containing them
  申请人：Hoechst Marion Roussel

  公开号：US20020002155A1

  公开（公告）日：2002-01-03

  The subject of the invention is the products of formula (I): 1 in which either R 1 represents halogen, hydroxyl, (C 1 -C 8 ) alkyloxy or (C 1 -C 12 ) acyloxy, and R 2 represents halogen or hydrogen, or R 1 and R 2 form together a double bond, Z is chosen from optionally substituted (C 1 -C 8 ) alkylthio, optionally substituted arylthio, (C 1 -C 8 ) alkyloxy, halogen, cyano, mercapto, thiocyanato and (CH 2 ) 0-1 —CO 2 H, optionally esterified, Y represents hydrogen or methyl, the dotted line in position 1-2 or 5-6 optionally representing a second bond, as well as their addition salts, their preparation process, the intermediates of this process and the pharmaceutical compositions containing them.

  本发明的主题是公式（I）的产物：1，其中R1表示卤素，羟基，（C1-C8）烷氧基或（C1-C12）酰氧基，R2表示卤素或氢，或者R1和R2一起形成双键，Z选择自可选取代的（C1-C8）烷硫基，可选取代的芳基硫基，（C1-C8）烷氧基，卤素，氰基，巯基，硫氰酸根和（CH2）0-1-CO2H，可选酯化，Y表示氢或甲基，位置1-2或5-6的点线可选地表示第二个键，以及它们的加成盐，制备过程，该过程的中间体和含有它们的药物组合物。
• JACOBSEN, E. JON;MCCALL, JOHN M.;AYER, DONALD E.;VAN, DOORNIK FRED J.;PAL+, J. MED. CHEM., 33,(1990) N, C. 1145-1151
  作者：JACOBSEN, E. JON、MCCALL, JOHN M.、AYER, DONALD E.、VAN, DOORNIK FRED J.、PAL+

  DOI：——

  日期：——
• DERIVES DE PREGNANE SANS SUBSTITUENT EN POSITION 17-ALPHA-, LEUR APPLICATION A TITRE DE MEDICAMENT, LEUR PROCEDE DE PREPARATION, LES INTERMEDIAIRES DE CE PROCEDE ET LES COMPOSITIONS LES CONTENANT
  申请人：HOECHST MARION ROUSSEL

  公开号：EP0898579B1

  公开（公告）日：2000-02-23
• US6274572B1
  申请人：——

  公开号：US6274572B1

  公开（公告）日：2001-08-14
• US6492536B2
  申请人：——

  公开号：US6492536B2

  公开（公告）日：2002-12-10