4-bromo-3-hydroxy-13α-estra-1,3,5(10)-trien-17-one

• 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: 4-bromo-3-hydroxy-13α-estra-1,3,5(10)-trien-17-one
• 英文别名: (8R,9S,13R,14S)-4-bromo-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• 化学式: C₁₈H₂₁BrO₂
• 分子量: 349.268
• InChiKey: NQFVJAYQCZUYON-LSIMKLPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  21.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-bromo-3-hydroxy-13α-estra-1,3,5(10)-trien-17-one 在 N-碘代丁二酰亚胺 、 三氟乙酸 作用下， 反应 2.0h， 以91%的产率得到4-bromo-3-hydroxy-2-iodo-13α-oestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  A环卤代雌酮衍生物AKR1C抑制特性的合成与评价

  摘要：

  摘要 酶 AKR1C 在受体前水平调节雌激素、雄激素和孕酮的作用，并且还与化学抗性有关。在重组 AKR1C 酶上研究了这些雌酮卤化物的活性。在 C-2 和 C-4 位具有卤原子的雌酮卤化物（13β-、13α-甲基-17-酮卤衍生物）是 AKR1C1 最有效的抑制剂。最低的 IC 50值是针对13α-差向异构体2 _2I,4Br 和2 _2I,4Cl（IC 50分别为 0.7 μM、0.8 μM），它们都选择性地抑制了 AKR1C1 异构体。13α-甲基-17-酮卤衍生物2 _2Br 和2 _4Cl 是最有效的 AKR1C2 抑制剂 (IC 50，分别为 1.5 μM 和 1.8 μM），对 AKR1C2 同种型具有高选择性。化合物1 _2Cl，4CL显示出最好的AKR1C3抑制，而且它也能抑制AKR1C1（KI：AKR1C1，0.69μM; AKR1C3，1.43μM）。这些数据表明，雌酮

  DOI：

  10.1080/14756366.2021.1937142
• 作为产物：
  描述：

  13α-estrone 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以53 mg的产率得到4-bromo-3-hydroxy-13α-estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Synthesis of A-ring halogenated 13α-estrone derivatives as potential 17β-HSD1 inhibitors

  摘要：

  13 alpha-Estrone and its 3-methyl or benzyl ether were halogenated in ring A with N-bromo- or N-iodosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin as electrophile triggers. The chemo- and regioselectivities of the reactions depended greatly on the nature of the substituent on C-3. Bromination of the ethers led to 2- and 4-regioisomers. Bis-halogenation occurred only in the case of the phenolic derivative. Iodination and bromination resulted in similar products, except that the 3-benzyl ether could not be iodinated under the applied conditions. The potential inhibitory action of the new halogenated 13 alpha-estrones on human 17 beta-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Some compounds proved to be effective inhibitors, with IC50 values in the submicromolar range. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2015.10.008

文献信息

• Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors
  作者：Rebeka Jójárt、Szabolcs Pécsy、György Keglevich、Mihály Szécsi、Réka Rigó、Csilla Özvegy-Laczka、Gábor Kecskeméti、Erzsébet Mernyák

  DOI：10.3762/bjoc.14.262

  日期：——

  inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by in vitro radiosubstrate incubation methods. None of the test compounds inhibited the STS markedly. The structure-activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17β-HSD1 enzyme with

  通过Hirao反应合成了新的2-或4-膦酸酯化的13α-雌酮衍生物。在微波辐射下，使用Pd（PPh3）4作为催化剂，将13α-雌酮的溴区域异构体（2-或4-）及其3-苄基或3-甲基醚与亚磷酸二乙酯或二苯基膦氧化物反应。通过测量级联蓝摄取量，研究了新化合物对有机阴离子转运多肽OATP2B1转运功能的影响。具有3-苄基醚功能的衍生物显示出显着的亚微摩尔OATP2B1抑制活性。通过体外放射性底物孵育方法研究了这些化合物对人胎盘类固醇硫酸酯酶（STS）和17β-羟基类固醇脱氢酶1型同工酶（17β-HSD1）的抑制作用。没有一种测试化合物能明显抑制STS。结构-活性关系评估表明，2-取代的3-羟基衍生物能够以亚微摩尔IC 50值抑制17β-HSD1酶。已经确定了双重OATP2B1和17β-HSD1抑制剂。
• Pd-catalyzed Suzuki–Miyaura couplings and evaluation of 13α-estrone derivatives as potential anticancer agents
  作者：Rebeka Jójárt、Hazhmat Ali、Gergely Horváth、Zoltán Kele、István Zupkó、Erzsébet Mernyák

  DOI：10.1016/j.steroids.2020.108731

  日期：2020.12

  their potent multiple bioactivity, including anticancer activity. 3-OH or 3-OBn derivatives of 2- or 4-[(subst.) phenyl]-13α-estrone as potential antiproliferative agents have been synthesized via facile, microwave-induced, Pd-catalyzed Suzuki-Miyaura coupling. 2- or 4-Halogenated 13α-estrone derivatives have been reacted with (4-subst.)phenylboronic acids using Pd(PPh3)4 as catalyst. The nature of para

  13α-雌酮具有强大的多重生物活性，包括抗癌活性，因此具有重要价值。2- 或 4-[(subst.) 苯基]-13α-雌酮的 3-OH 或 3-OBn 衍生物作为潜在的抗增殖剂已通过简便的微波诱导 Pd 催化 Suzuki-Miyaura 偶联合成。使用 Pd(PPh3)4 作为催化剂，2-或 4-卤化 13α-雌酮衍生物与 (4-subst.) 苯基硼酸反应。引入的苯基上的对位取代基的性质不影响偶联的结果。某些新合成的化合物对妇科来源的人粘附癌细胞系显示出显着的抗增殖作用。揭示了重要的构效关系，
• Synthesis of A-ring halogenated 13α-estrone derivatives as potential 17β-HSD1 inhibitors
  作者：Ildikó Bacsa、Rebeka Jójárt、Gyula Schneider、János Wölfling、Péter Maróti、Bianka Edina Herman、Mihály Szécsi、Erzsébet Mernyák

  DOI：10.1016/j.steroids.2015.10.008

  日期：2015.12

  13 alpha-Estrone and its 3-methyl or benzyl ether were halogenated in ring A with N-bromo- or N-iodosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin as electrophile triggers. The chemo- and regioselectivities of the reactions depended greatly on the nature of the substituent on C-3. Bromination of the ethers led to 2- and 4-regioisomers. Bis-halogenation occurred only in the case of the phenolic derivative. Iodination and bromination resulted in similar products, except that the 3-benzyl ether could not be iodinated under the applied conditions. The potential inhibitory action of the new halogenated 13 alpha-estrones on human 17 beta-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Some compounds proved to be effective inhibitors, with IC50 values in the submicromolar range. (C) 2015 Elsevier Inc. All rights reserved.
• Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives
  作者：Maša Sinreih、Rebeka Jójárt、Zoltán Kele、Tomaž Büdefeld、Gábor Paragi、Erzsébet Mernyák、Tea Lanišnik Rižner

  DOI：10.1080/14756366.2021.1937142

  日期：2021.1.1

  atoms at both C-2 and C-4 positions (13β-, 13α-methyl-17-keto halogen derivatives) were the most potent inhibitors of AKR1C1. The lowest IC50 values were for the 13α-epimers 2_2I,4Br and 2_2I,4Cl (IC50, 0.7 μM, 0.8 μM, respectively), both of which selectively inhibited the AKR1C1 isoform. The 13α-methyl-17-keto halogen derivatives 2_2Br and 2_4Cl were the most potent inhibitors of AKR1C2 (IC50, 1.5 μM

  摘要 酶 AKR1C 在受体前水平调节雌激素、雄激素和孕酮的作用，并且还与化学抗性有关。在重组 AKR1C 酶上研究了这些雌酮卤化物的活性。在 C-2 和 C-4 位具有卤原子的雌酮卤化物（13β-、13α-甲基-17-酮卤衍生物）是 AKR1C1 最有效的抑制剂。最低的 IC 50值是针对13α-差向异构体2 _2I,4Br 和2 _2I,4Cl（IC 50分别为 0.7 μM、0.8 μM），它们都选择性地抑制了 AKR1C1 异构体。13α-甲基-17-酮卤衍生物2 _2Br 和2 _4Cl 是最有效的 AKR1C2 抑制剂 (IC 50，分别为 1.5 μM 和 1.8 μM），对 AKR1C2 同种型具有高选择性。化合物1 _2Cl，4CL显示出最好的AKR1C3抑制，而且它也能抑制AKR1C1（KI：AKR1C1，0.69μM; AKR1C3，1.43μM）。这些数据表明，雌酮