ethyl 3,17β-dihydroxy-1,3,5-estratriene-17α-acetate | 95764-52-6

• 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: ethyl 3,17β-dihydroxy-1,3,5-estratriene-17α-acetate
• 英文别名: ethyl 2-[(8R,9S,13S,14S,17R)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]acetate
• CAS: 95764-52-6
• 化学式: C₂₂H₃₀O₄
• 分子量: 358.478
• InChiKey: BZLFXLCUPYYHAL-PIBZIWMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3,17β-dihydroxy-1,3,5-estratriene-17α-acetate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以63%的产率得到3,17β-dihydroxy-1,3,5-estratriene-17α-acetic acid
  参考文献：
  名称：

  Effect of 17-α-Ethynylestradiol on Activities of Cytochrome P450 2B (P450 2B) Enzymes: Characterization of Inactivation of P450s 2B1 and 2B6 and Identification of Metabolites

  摘要：

  17-α-乙炔雌二醇（17EE）以机制为基础的方式使纯化复溶的大鼠肝细胞色素P450（P450）2B1和人类P450 2B6失活。与17EE共同孵育时，P450 2B2或2B4几乎没有或没有观察到失活。P450 2B1和2B6的失活完全依赖于NADPH和17EE，并遵循伪一级动力学。在30°C下，P450 2B1和2B6的最大失活速率常数分别为0.2和0.03 min⁻¹。对于P450 2B1和2B6，表观K_I分别为11和0.8 μM。将P450 2B1与17EE和NADPH共同孵育20分钟，酶活性损失达75%，同时酶形成还原CO络合物的能力损失为20%至25%。在P450 2B6中，酶活性损失达83%，而CO还原光谱的损失为5%至10%。17EE与P450 2B1和2B6的推算分配比分别为21和13。将另一种底物与17EE同时孵育可保护这两种酶免于失活。对P450 2B1和2B6的放射性标记17EE结合的标记计量比为1.3:1。这些结果表明，17EE以机制为基础的方式使P450 2B1和2B6失活，主要通过17EE的反应性中间体与其Apoprotein结合。对17EE代谢物的分析表明，失活的2B酶主要在于其产生两种P450 2B2或2B4未产生的代谢物的能力。

  DOI：

  10.1124/jpet.300.2.549
• 作为产物：
  描述：

  雌酚酮 、 溴乙酸乙酯 在 锌 作用下， 以 乙醚 、 苯 为溶剂， 反应 5.0h， 以57%的产率得到ethyl 3,17β-dihydroxy-1,3,5-estratriene-17α-acetate
  参考文献：
  名称：

  Effect of 17-α-Ethynylestradiol on Activities of Cytochrome P450 2B (P450 2B) Enzymes: Characterization of Inactivation of P450s 2B1 and 2B6 and Identification of Metabolites

  摘要：

  17-α-乙炔雌二醇（17EE）以机制为基础的方式使纯化复溶的大鼠肝细胞色素P450（P450）2B1和人类P450 2B6失活。与17EE共同孵育时，P450 2B2或2B4几乎没有或没有观察到失活。P450 2B1和2B6的失活完全依赖于NADPH和17EE，并遵循伪一级动力学。在30°C下，P450 2B1和2B6的最大失活速率常数分别为0.2和0.03 min⁻¹。对于P450 2B1和2B6，表观K_I分别为11和0.8 μM。将P450 2B1与17EE和NADPH共同孵育20分钟，酶活性损失达75%，同时酶形成还原CO络合物的能力损失为20%至25%。在P450 2B6中，酶活性损失达83%，而CO还原光谱的损失为5%至10%。17EE与P450 2B1和2B6的推算分配比分别为21和13。将另一种底物与17EE同时孵育可保护这两种酶免于失活。对P450 2B1和2B6的放射性标记17EE结合的标记计量比为1.3:1。这些结果表明，17EE以机制为基础的方式使P450 2B1和2B6失活，主要通过17EE的反应性中间体与其Apoprotein结合。对17EE代谢物的分析表明，失活的2B酶主要在于其产生两种P450 2B2或2B4未产生的代谢物的能力。

  DOI：

  10.1124/jpet.300.2.549

文献信息

• Isoxazoles with antipicornavirus activity
  作者：Guy D. Diana、M. A. McKinlay、C. J. Brisson、E. S. Zalay、J. V. Miralles、U. J. Salvador

  DOI：10.1021/jm00383a010

  日期：1985.6

  The synthesis and evaluation of a series of 3,5-disubstituted isoxazoles as antipicornavirus agents have led to the discovery of several compounds effective in vitro against rhinovirus type 2 and poliovirus type 2. Compound 32 was found more effective than 4',6-dichloroflavan against both viruses and was evaluated orally in mice infected intracerebrally with polio-2. At 31 mg/kg bid, compound 32 showed a 53% survival rate as compared to 22% for the nonmedicated animals.
• Design, Synthesis, and Biological Evaluation of Ellipticine−Estradiol Conjugates
  作者：Rajesh Devraj、John F. Barrett、Jeffrey A. Fernandez、John A. Katzenellenbogen、Mark Cushman

  DOI：10.1021/jm9602930

  日期：1996.1.1

  Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) positions of ellipticine. The ellipticine-estradiol conjugates were evaluated for their abilities to bind to estrogen receptors, to inhibit topoisomerase II, and for their cytotoxicities in human cancer cell lines. Conjugates 3 and 5 displayed weak binding affinities of 0.132 and 0.303 for the estrogen receptor (relative to estradiol = 100), while conjugate 4 did not show any detectable binding to the estrogen receptor. Compound 3 was a moderate inhibitor of topoisomerase II (IC50 24.1 mu M), while 4 and 5 were inactive. Conjugate 3 was consistently more cytotoxic (GI(50) values 1-10 mu M) than compounds 4 and 5 (GI(50) values 10-100 mu M) in a variety of human cancer cell lines, None of the compounds displayed any selectivity for estrogen-receptor positive cell lines, which probably reflects their weak affinities for estrogen receptors.
• Effect of 17-α-Ethynylestradiol on Activities of Cytochrome P450 2B (P450 2B) Enzymes: Characterization of Inactivation of P450s 2B1 and 2B6 and Identification of Metabolites
  作者：Ute M. Kent、Danielle E. Mills、Rajendram V. Rajnarayanan、William L. Alworth、Paul F. Hollenberg

  DOI：10.1124/jpet.300.2.549

  日期：2002.2.1

  17-α-Ethynylestradiol (17EE) inactivated purified, reconstituted rat hepatic cytochrome P450 (P450) 2B1 and human P450 2B6 in a mechanism-based manner. Little or no inactivation was observed when P450s 2B2 or 2B4 were incubated with 17EE. The inactivation of P450s 2B1 and 2B6 was entirely dependent on both NADPH and 17EE and followed pseudo-first order kinetics. The maximal rate constants for the inactivation of P450s 2B1 and 2B6 at 30°C were 0.2 and 0.03 min−1, respectively. For P450s 2B1 and 2B6 the apparent K I was 11 and 0.8 μM, respectively. Incubation of P450 2B1 with 17EE and NADPH for 20 min resulted in a 75% loss in enzymatic activity and a concurrent 20 to 25% loss of the enzyme's ability to form a reduced CO complex. With P450 2B6, an 83% loss in enzymatic activity and a 5 to 10% loss in the CO reduced spectrum were observed. The extrapolated partition ratios for 17EE with P450 2B1 and 2B6 were 21 and 13, respectively. Simultaneous incubation of an alternate substrate together with 17EE protected both enzymes from inactivation. A 1.3:1 stoichiometry of labeling for binding of the radiolabeled 17EE to P450 2B1 and 2B6 was seen. These results indicate that 17EE inactivates P450s 2B1 and 2B6 in a mechanism-based manner, primarily by the binding of a reactive intermediate of 17EE to the apoprotein. Analysis of the 17EE metabolites showed that 2B enzymes that become inactivated differ primarily by their ability to generate two metabolites that were not produced by P450s 2B2 or 2B4.

  17-α-乙炔雌二醇（17EE）以机制为基础的方式使纯化复溶的大鼠肝细胞色素P450（P450）2B1和人类P450 2B6失活。与17EE共同孵育时，P450 2B2或2B4几乎没有或没有观察到失活。P450 2B1和2B6的失活完全依赖于NADPH和17EE，并遵循伪一级动力学。在30°C下，P450 2B1和2B6的最大失活速率常数分别为0.2和0.03 min⁻¹。对于P450 2B1和2B6，表观K_I分别为11和0.8 μM。将P450 2B1与17EE和NADPH共同孵育20分钟，酶活性损失达75%，同时酶形成还原CO络合物的能力损失为20%至25%。在P450 2B6中，酶活性损失达83%，而CO还原光谱的损失为5%至10%。17EE与P450 2B1和2B6的推算分配比分别为21和13。将另一种底物与17EE同时孵育可保护这两种酶免于失活。对P450 2B1和2B6的放射性标记17EE结合的标记计量比为1.3:1。这些结果表明，17EE以机制为基础的方式使P450 2B1和2B6失活，主要通过17EE的反应性中间体与其Apoprotein结合。对17EE代谢物的分析表明，失活的2B酶主要在于其产生两种P450 2B2或2B4未产生的代谢物的能力。