17α-hydroxy-17β-methyl-16β-phenyl-D-homopregna-4,6-diene-3,17a-dione | 215655-87-1

• 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: 17α-hydroxy-17β-methyl-16β-phenyl-D-homopregna-4,6-diene-3,17a-dione
• 英文别名: (2R,3R,4aS,4bR,10aR,10bS,12aS)-2-hydroxy-2,10a,12a-trimethyl-3-phenyl-4,4a,4b,9,10,10b,11,12-octahydro-3H-chrysene-1,8-dione
• CAS: 215655-87-1
• 化学式: C₂₇H₃₂O₃
• 分子量: 404.549
• InChiKey: YUAFKTCTZIWJCR-XLGRHVQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  、 17α-hydroxy-17β-methyl-16β-phenyl-D-homopregna-4,6-diene-3,17a-dione 在 对甲苯磺酸 作用下， 反应 2.0h， 以0.1 g的产率得到17β-methyl-16β-phenyl-17α-(2-fluorophenyl)acetoxy-D-homoandrost-4,6-diene-3,17a-dione
  参考文献：
  名称：

  New-D-homoandrost-4,6-diene derivatives as potent progesterone receptor antagonist

  摘要：

  The aim of this study was to synthesize three different D-homoandrostadiene derivatives (2-4) and study their biological activity. We carried out in vivo and in vitro experiments using female cycling mice, which were synchronized for estrus with luteinizing hormone-releasing hormone (LHRH) and injected with the steroidal compounds. It was also determined the binding of these compounds to the progesterone receptors (PR). Since these steroids have a new D-homoandrostandienone skeleton in their molecular structure, it was of interest also to study their binding to the androgen receptors (AR).After LHRH treatment, the mice of the control group showed the presence of 14 +/- 4 corpus lutea in the ovary whereas the animals treated with steroids 2-4, with RBAs of 100%, exhibited 11 +/- 7, 12 +/- 2, and 10 +/- 4 respectively. As a result of this study, it is evident that these steroids did not inhibit the ovulation in these animals.The uterus of the control group, showed the typical progestational activity with an enlarged endometrial thickness with a secretory activity. However, the endometrium of the mice treated with steroids 2-4 did not show an enlargement of the endometrium and no secretory activity could be detected. This fact indicates that compounds 2-4 had antagonistic activity in this tissue.The overall data show that steroids 2-4 are antagonists of the PR. However, they do not bind to the AR. These results also demonstrate that 2-4 have an anti progestational activity in vivo, but do not decrease the number of corpus lutea in the ovary of mice treated with LHRH. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2009.11.001
• 作为产物：
  描述：

  16-脱氢孕烯醇酮乙酸酯 在 吡啶 、 sodium hydroxide 、 copper(l) iodide 、 高氯酸 、 双氧水 、 溴 、 lithium carbonate 、 对甲苯磺酸 、 lithium bromide 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 106.0h， 生成 17α-hydroxy-17β-methyl-16β-phenyl-D-homopregna-4,6-diene-3,17a-dione
  参考文献：
  名称：

  Evaluation of New Pregnane Derivatives as 5.ALPHA.-Reductase Inhibitor.

  摘要：

  本研究的目的是合成几种新的孕烷衍生物，并将它们作为抗雄激素进行评估。从市售的 16-脱氢孕烯醇酮醋酸酯（7）中，合成了两种新的类固醇化合物：17α-hydroxy-17β-methyl-16β-phenyl-D-homoandrosta-1, 4.6-triene-3, 20-dione (18) 和 17α-acetoxy-17β-methyl-16β-phenyl-D-homoandrosta-1, 4.6-triene-3, 20-dione (19)。新化合物 18 和 19 以及之前合成的中间体 7、8、13、16 和 17 的 5α 还原酶抑制作用在三种不同的模型中进行了测定：性腺切除的仓鼠侧腹器官直径大小、侧腹器官脂质中[1, 2-14C]sodium acetate 的结合以及甲壳青霉将[3H]睾酮（T）转化为[3H]双氢睾酮（DHT）。对这些类固醇的评估是在三个不同对照组的基础上进行的：一组用药物治疗，第二组用睾酮治疗，第三组用睾酮加非那雄胺治疗。这项工作的药理结果表明，T 能显著增加仓鼠腹侧器官上色素斑的直径（p<0.05），并能显著增加性腺切除仓鼠腹侧器官中脂质中标记的醋酸钠的掺入量（每个腺体从 0.125 到 0.255 nmol）。在这项研究中，我们还观察到甲壳青霉肉汤将[3H]T转化为[3H]DHT的方式与侧腹器官的转化方式类似。所有实验都表明，非那雄胺以及类固醇 7、8、13、16-19 能显著减少甲壳青霉中 T 向 DHT 的转化。这些化合物还能减小侧腹器官中色素斑的大小，并减少放射性标记的醋酸钠在脂质中的结合；T 和对照样本（仅用载体处理）被用来进行比较。显然，4,6-二烯-3,20-二酮分子和 C-17 酯基的存在对所用参数产生了更大的抑制作用。该研究的数据还表明，用于药理评估的三种模型表现出的结果具有可比性。

  DOI：

  10.1248/cpb.49.525

文献信息

• Antiandrogenic Effect of 16-Substituted, Non-substituted and D-Homopregnane Derivatives.
  作者：Eugene A. BRATOEFF、H. HERRERA、E. RAMIRES、K. SOLORZANO、E. MURILLO、A. QUIROZ、M. CABEZA

  DOI：10.1248/cpb.48.1249

  日期：——

  The pharmacological activities of 12 pregnane derivatives (4-15) were determined on gonadectomized male hamster flank organs and seminal vesicles as antiandrogens and as 5α-reductase inhibitors. The results from this study indicate that subcutaneous injection of testosterone for 3 d increased the diameter of the pigmented spot in the flank organs, whereas finasteride when injected with testosterone decreased the size of the spot significantly when steroids 4-15 were injected together with testosterone, the diameter of the flank organs of gonadectomized male hamsters, decreased significantly (p<0.005) compared to testosterone. Compound 11 was the most active steroid and reduced the diameter of the pigmented spot more than the other synthesized steroids or finasteride. Subcutaneous injections of testosterone to gonadectomized animals restore the seminal vesicle size lost upon castration. Injection of testosterone plus finasteride decreased significantly the weight of these glands (p<0.005). Steroids 5-15 when injected with testosterone decreased the weight of the seminal vesicles compared to testosterone. Finasteride is a good inhibitor of the conversion of testosterone to dihydrotestosterone (DHT) (low formation of DHT) measured as pmole of DHT/g of protein/h. Steroids 6-15 inhibited the conversion of testosterone to DHT as compared to testosterone however finasteride and 10 appeared to be the most effective compounds. Castration increases the protein content of the seminal vesicles (control) expressed as μg/mg of tissues. Testosterone tends to decrease it significantly, as did compounds 4, 5, 7, 9, and 15. We demonstrated that DHT as well as cyproterone acetate and steroids 5, 6, 8, 9, 11, and 14 at increasing non radioactive steroid concentration, inhibited the binding of [3H]DHT to cytosolic androgen receptor (AR), as indicated by its K1 values. However, 4, 7, 10, 12, and 13 did not have any inhibitory effect.

  本研究测定了12种孕烷衍生物（4-15）作为抗雄激素和5α还原酶抑制剂在性腺切除的雄性仓鼠侧腹器官和精囊上的药理活性。研究结果表明，皮下注射睾酮 3 d 后，仓鼠侧腹器官色素斑的直径增大，而与睾酮同时注射非那雄胺后，色素斑的大小明显缩小。化合物 11 是活性最强的类固醇，它比其他合成类固醇或非那雄胺更能减少色斑的直径。对性腺切除的动物皮下注射睾酮可恢复阉割后丧失的精囊大小。注射睾酮和非那雄胺可显著减少这些腺体的重量（p<0.005）。与睾酮相比，与睾酮一起注射的类固醇5-15会减少精囊的重量。非那雄胺能很好地抑制睾酮向双氢睾酮（DHT）的转化（DHT的形成较低），以DHT/克蛋白质/小时的pmole来衡量。与睾酮相比，类固醇 6-15 可抑制睾酮向 DHT 的转化，但非那雄胺和 10 似乎是最有效的化合物。阉割会增加精囊（对照组）的蛋白质含量，单位为微克/毫克组织。睾酮和化合物 4、5、7、9 和 15 都会显著降低精囊蛋白含量。我们的研究表明，DHT、醋酸环丙孕酮和类固醇 5、6、8、9、11 和 14 在非放射性类固醇浓度增加的情况下，会抑制 [3H]DHT 与细胞膜雄激素受体（AR）的结合，如其 K1 值所示。然而，4、7、10、12 和 13 没有任何抑制作用。
• ——
  作者：Manuel Soriano-García、Simón Hernández-Ortega、Eugene Bratoeff、Norma Valencia、Elena Ramírez、Gregoria Flores

  DOI：10.1023/a:1021729007943

  日期：——

  The title compound is C29H34O4, tetragonal, P4(3), a = b = 10.310(1), c = 23.871(2)Angstrom. The A, B, C, and D rings adopt envelope, half-chair, chair, and distorted chair conformations, respectively. The phenyl ring is planar. The methyl substituents at the A/B, C/D, and at C(17) are axial; and the -OCOCH3 group at C(17) and phenyl ring at C(16) are equatorial. The molecules in the crystal are held together by van der Waals forces and several C-H ... O hydrogen bond interactions.