(1R,3aR,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one | 635311-73-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,3aR,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
• CAS: 635311-73-8
• 化学式: C₂₀H₂₉NO₂S
• 分子量: 347.522
• InChiKey: UWYPTYAWFVNDAY-HSHCSMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3aR,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one 在 正丁基锂 、 氢氟酸 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 17.0h， 生成 (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol
  参考文献：
  名称：

  Potent, Selective and Low-Calcemic Inhibitors of CYP24 Hydroxylase:  24-Sulfoximine Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃

  摘要：

  A dozen 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D-3 were prepared, differing not only at the stereogenic sulfoximine stereocenter but also at the A-ring. Although these sulfoximines were not active transcriptionally and were only very weakly antiproliferative, some of them are powerful hydroxylase enzyme inhibitors. Specifically, 24-(S)-NH phenyl sulfoximine 3a is an extremely potent CYP24 inhibitor (IC50 = 7.4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC50 > 1000 nM) and CYP27B (IC50 = 554 nM).

  DOI：

  10.1021/jm040129+
• 作为产物：
  描述：

  (8S,20S)-de-A,B-8-triethylsilyloxy-20-(iodomethyl)-pregnane 在 六甲基磷酰三胺 、 重铬酸吡啶 、 正丁基锂 、 Celite 、 氢氟酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.5h， 生成 (1R,3aR,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
  参考文献：
  名称：

  Potent, Selective and Low-Calcemic Inhibitors of CYP24 Hydroxylase:  24-Sulfoximine Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃

  摘要：

  A dozen 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D-3 were prepared, differing not only at the stereogenic sulfoximine stereocenter but also at the A-ring. Although these sulfoximines were not active transcriptionally and were only very weakly antiproliferative, some of them are powerful hydroxylase enzyme inhibitors. Specifically, 24-(S)-NH phenyl sulfoximine 3a is an extremely potent CYP24 inhibitor (IC50 = 7.4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC50 > 1000 nM) and CYP27B (IC50 = 554 nM).

  DOI：

  10.1021/jm040129+

文献信息

• [EN] 24-SULFOXIMINE VITAMIN D3 COMPOUNDS<br/>[FR] COMPOSES DE TYPE 24-SULFOXIMINE VITAMINE D3
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2003106411A1

  公开（公告）日：2003-12-24

  The present invention provides novel sulfoximine compounds, compositions comprising these compounds and methods of using these compounds as inhibitors of CYP24. In particular, the compounds of the invention are useful for treating diseases which benefit from a modulation of the levels of 1α,25-dihydroxy vitamin D3, for example, cell-proliferative disorders.

  本发明提供了新型亚砜胺化合物，包括这些化合物的组合物以及使用这些化合物作为CYP24抑制剂的方法。特别是，本发明的化合物对于治疗受益于调节1α,25-二羟基维生素D3水平的疾病非常有用，例如细胞增殖性疾病。