3-(methylsulfinyl)estra-1,3,5(10)-trien-17-one | 148259-09-0

• 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: 3-(methylsulfinyl)estra-1,3,5(10)-trien-17-one
• 英文别名: 3-(methylsulfanyl)estra-1(10),2,4-trien-17-one；3-thiomethylestra-1,3,5(10)-trien-17-one；(8R,9S,13S,14S)-13-methyl-3-methylsulfanyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 148259-09-0
• 化学式: C₁₉H₂₄OS
• 分子量: 300.465
• InChiKey: LGRZLOREAOXTMU-VXNCWWDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(methylsulfinyl)estra-1,3,5(10)-trien-17-one 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 48.0h， 以85%的产率得到3-(methylsulfonyl)estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Synthesis and biochemical studies of estrone sulfatase inhibitors

  摘要：

  The synthesis and biochemical evaluation of estrone sulfatase inhibitors are described. Inhibitors were designed through modifications of the substrate estrone sulfate. An in vitro assay using the microsomal fraction isolated from human term placenta was used to evaluate sulfatase inhibitory activity. All the inhibitors (except sulfonyl chloride analog) exhibited low inhibitory activities in the screening assay. Sulfonyl chloride analog is a strong inhibitor, which caused 91.5% inhibition of the enzymatic activity at 300 microM.

  DOI：

  10.1016/0039-128x(93)90045-o
• 作为产物：
  描述：

  3-<(N,N-dimethylcarbamoyl)thio>estra-1,3,5(10)-trien-17-one 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-(methylsulfinyl)estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Synthesis and biochemical studies of estrone sulfatase inhibitors

  摘要：

  The synthesis and biochemical evaluation of estrone sulfatase inhibitors are described. Inhibitors were designed through modifications of the substrate estrone sulfate. An in vitro assay using the microsomal fraction isolated from human term placenta was used to evaluate sulfatase inhibitory activity. All the inhibitors (except sulfonyl chloride analog) exhibited low inhibitory activities in the screening assay. Sulfonyl chloride analog is a strong inhibitor, which caused 91.5% inhibition of the enzymatic activity at 300 microM.

  DOI：

  10.1016/0039-128x(93)90045-o

文献信息

• Targeting Cytochrome P450 (CYP) 1B1 Enzyme with Four Series of A-Ring Substituted Estrane Derivatives: Design, Synthesis, Inhibitory Activity, and Selectivity
  作者：Raphaël Dutour、Jenny Roy、Francisco Cortés-Benítez、René Maltais、Donald Poirier

  DOI：10.1021/acs.jmedchem.8b00907

  日期：2018.10.25

  CYP1B1 inhibitors over CYP1A1, we synthesized four series of estrane derivatives: (1) 12 estrone (E1)- and 17β-estradiol (E2)-derivatives bearing a 3- or a 4-pyridinyl core at C2, C3, or C4, (2) eight estrane derivatives with different sulfur groups at C3, (3) 19 E1- and E2-derivatives bearing distinct aryls at C2, and (4) five D-ring derivatives. E2-derivatives were more active than oxidized E1-analogues

  细胞色素P450（CYP）1B1参与致癌物的生物激活和耐药性。为了获得相对于CYP1A1的选择性CYP1B1抑制剂，我们合成了四个系列的雌激素衍生物：（1）12个雌酮（E1）-和17β-雌二醇（E2）-衍生物，在C2，C3或C3处带有3-或4-吡啶基核心C4，（2）在C3具有八个不同硫基的雌激素衍生物，（3）在C2具有不同芳基的19个E1-和E2-衍生物，以及（4）五个D环衍生物。E2衍生物比氧化的E1类似物更具活性，因此突出了17β-OH在与CYP1B1相互作用中的关键作用。2-（4-氟苯基）-E2是最好的CYP1B1抑制剂（IC 50= 0.24μM），相对于CYP1A1的选择性指数（SI）为20。此外，添加C17α-乙炔基作为D环修饰可将选择性指数提高至25，而活性几乎没有损失（IC 50 = 0.37μM）。我们的对接结果表明，这些化合物比CYP1A1更适合CYP1B1结合位点。
• [EN] 3-NITROGEN OR SULPHUR SUBSTITUTED OESTRA-1,3,5(10),16-TETRAENE AKR1C3 INHIBITORS<br/>[FR] INHIBITEURS D'AKR1C3 DE TYPE ŒSTRA-1,3,5(10),16-TÉTRAÈNE SUBSTITUÉS PAR UN 3-AZOTE OU SOUFRE
  申请人：BAYER PHARMA AG

  公开号：WO2016037956A1

  公开（公告）日：2016-03-17

  The invention relates to AKR1C3 inhibitors of formula (I) and to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of bleeding disorders and endometriosis.

  该发明涉及式(I)的AKR1C3抑制剂，以及其制备方法，用于治疗和/或预防疾病的用途，以及用于生产治疗和/或预防疾病的药物的用途，特别是用于出血性疾病和子宫内膜异位症的治疗。
• 3-NITROGEN OR SULPHUR SUBSTITUTED OESTRA-1,3,5(10),16-TETRAENE AKR1C3 INHIBITORS
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP3194419A1

  公开（公告）日：2017-07-26