(8R,9S,13S,14S)-2-bromo-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one | 959393-66-9

• 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: (8R,9S,13S,14S)-2-bromo-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 959393-66-9
• 化学式: C₂₅H₂₇BrO₂
• 分子量: 439.392
• InChiKey: HVILBSKZZPFULR-UVYNTUDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (8R,9S,13S,14S)-2-bromo-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one 、 亚磷酸二异丙酯 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 0.5h， 以89%的产率得到diisopropyl (3-benzyloxy-estra-1,3,5(10)-trien-17-on-2-yl)phosphonate
  参考文献：
  名称：

  作为高亲和力有机阴离子转运多肽 2B1 (OATP2B1) 抑制剂的新型雌酮膦酸酯的设计、合成和生物学评价

  摘要：

  有机阴离子转运多肽 2B1 (OATP2B1) 是一种多特异性膜转运蛋白，介导各种外生和内生素的细胞摄取，包括药物和类固醇激素。OATP2B1 对类固醇激素的摄取增加可能会增加肿瘤增殖。因此，非常需要了解 OATP2B1 的底物/抑制剂识别和对其功能的抑制，例如在激素依赖性肿瘤中。为了确定与 OATP2B1 抑制相关的关键结构特征，我们在这里设计了对雌二醇骨架的四个位置的修饰。合成了在环 A 或环 D 处修饰的 13α- 或 13β-雌酮膦酸酯。Hirao 和 Cu(I) 催化的叠氮化物-炔烃点击反应是合成中的关键步骤。13β-衍生物通过 IC 显示出出色的 OATP2B1 抑制作用纳摩尔范围内的50 个值 (41–87 nM)。另外合成了 BODIPY-13α-雌酮缀合物，在类固醇的C-3- O 处进行了修饰，在三唑部分和 BODIPY 核心之间包含一个四碳接头。荧光偶联物显示出有效的亚微摩尔

  DOI：

  10.1016/j.bioorg.2021.104914
• 作为产物：
  描述：

  2-bromoestrone 、 溴甲苯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (8R,9S,13S,14S)-2-bromo-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  Chemical Synthesis of Six Novel 17β-Estradiol and Estrone Dimers and Study of Their Formation Catalyzed by Human Cytochrome P450 Isoforms

  摘要：

  Our earlier studies have shown that over 20 nonpolar 17 beta-estradiol metabolite peaks were detected following incubations of radioactive 17 beta-estradiol with human liver microsomes or recombinant human cytochrome P450 isoforms in the presence of NADPH as a cofactor. The structures of two representative nonpolar metabolites were identified earlier as dimers of 17 beta-estradiol linked through a diaryl ether bond between the C-3 phenolic oxygen of one molecule and the C-2 or C-4 aromatic carbon of another. Six additional putative dimers between estrone and 17 beta-estradiol with structures similar to the two identified ones were synthesized in this study. Using these newly synthesized estrogen dimers as reference standards, we demonstrated that incubations of human liver microsomes or various human cytochrome P450 isoforms with estrone or 17-estradiol alone or two estrogens in combination in the presence of NADPH as a cofactor resulted in the formation of all eight estrogen dimers in varying quantities.

  DOI：

  10.1021/jm0707323

文献信息

• Chemical Synthesis of Six Novel 17β-Estradiol and Estrone Dimers and Study of Their Formation Catalyzed by Human Cytochrome P450 Isoforms
  作者：Aaron Yun Chen、Anthony J. Lee、Xiang-Rong Jiang、Bao Ting Zhu

  DOI：10.1021/jm0707323

  日期：2007.11.1

  Our earlier studies have shown that over 20 nonpolar 17 beta-estradiol metabolite peaks were detected following incubations of radioactive 17 beta-estradiol with human liver microsomes or recombinant human cytochrome P450 isoforms in the presence of NADPH as a cofactor. The structures of two representative nonpolar metabolites were identified earlier as dimers of 17 beta-estradiol linked through a diaryl ether bond between the C-3 phenolic oxygen of one molecule and the C-2 or C-4 aromatic carbon of another. Six additional putative dimers between estrone and 17 beta-estradiol with structures similar to the two identified ones were synthesized in this study. Using these newly synthesized estrogen dimers as reference standards, we demonstrated that incubations of human liver microsomes or various human cytochrome P450 isoforms with estrone or 17-estradiol alone or two estrogens in combination in the presence of NADPH as a cofactor resulted in the formation of all eight estrogen dimers in varying quantities.
• Design, synthesis and biological evaluation of novel estrone phosphonates as high affinity organic anion-transporting polypeptide 2B1 (OATP2B1) inhibitors
  作者：Rebeka Jójárt、Réka Laczkó-Rigó、Máté Klement、Gabriella Kőhl、Gábor Kecskeméti、Csilla Özvegy-Laczka、Erzsébet Mernyák

  DOI：10.1016/j.bioorg.2021.104914

  日期：2021.7

  outstanding OATP2B1 inhibitory action with IC50 values in the nanomolar range (41–87 nM). A BODIPY-13α-estrone conjugate was additionally synthesized, modified at C-3-O of the steroid, containing a four-carbon linker between the triazole moiety and the BODIPY core. The fluorescent conjugate displayed efficient, submicromolar OATP2B1 inhibitory potency. The newly identified inhibitors and the structure–activity

  有机阴离子转运多肽 2B1 (OATP2B1) 是一种多特异性膜转运蛋白，介导各种外生和内生素的细胞摄取，包括药物和类固醇激素。OATP2B1 对类固醇激素的摄取增加可能会增加肿瘤增殖。因此，非常需要了解 OATP2B1 的底物/抑制剂识别和对其功能的抑制，例如在激素依赖性肿瘤中。为了确定与 OATP2B1 抑制相关的关键结构特征，我们在这里设计了对雌二醇骨架的四个位置的修饰。合成了在环 A 或环 D 处修饰的 13α- 或 13β-雌酮膦酸酯。Hirao 和 Cu(I) 催化的叠氮化物-炔烃点击反应是合成中的关键步骤。13β-衍生物通过 IC 显示出出色的 OATP2B1 抑制作用纳摩尔范围内的50 个值 (41–87 nM)。另外合成了 BODIPY-13α-雌酮缀合物，在类固醇的C-3- O 处进行了修饰，在三唑部分和 BODIPY 核心之间包含一个四碳接头。荧光偶联物显示出有效的亚微摩尔