(8R,9S,13S,14S,17S )-13-methyl-4',5',6,7,8,9,11,12,13,14,15,16-dodecahydrospiro [cyclopenta[a]phenanthrene17,2'pyran]-6'(3'H)-one | 243637-91-4

• 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,17S )-13-methyl-4',5',6,7,8,9,11,12,13,14,15,16-dodecahydrospiro [cyclopenta[a]phenanthrene17,2'pyran]-6'(3'H)-one
• 英文别名: (8R,9S,13S,14S,17S)-13-methylspiro[7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17,6'-oxane]-2'-one
• CAS: 243637-91-4
• 化学式: C₂₂H₂₈O₂
• 分子量: 324.463
• InChiKey: JFEVGYBOFUOWOA-DGYCAGFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 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,17S )-13-methyl-4',5',6,7,8,9,11,12,13,14,15,16-dodecahydrospiro [cyclopenta[a]phenanthrene17,2'pyran]-6'(3'H)-one 、 碘甲烷 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 以36%的产率得到(8R,9S,13S,14S,17R)-5',13-dimethyl-4',5',6,7,8,9,11,12,13,14,15,16-dodecahydrospiro [cyclopenta[a]phenanhrene-17,2'-pyran]-6'(3'H)-one
  参考文献：
  名称：

  Steroidal lactones as inhibitors of 17β-hydroxysteroid dehydrogenase type 5: Chemical synthesis, enzyme inhibitory activity, and assessment of estrogenic and androgenic activities

  摘要：

  Androgens are well known to play a predominant role in prostate cancer and other androgen-dependent diseases. To decrease the level of androgen testosterone in the prostate, we are interested in developing inhibitors of 17 beta-hydroxysteroid dehydrogenase type 5 (17 beta-HSD5). This enzyme expressed in the prostate is one of the two enzymes able to convert 4-androstene-3,17-dione into testosterone. From a screening study, it was found that a series of steroid derivatives bearing a lactone on D-ring demonstrated potent inhibition of 17 beta-HSD5 over-expressed in HEK-293 cells. The results of enzymatic assays using intact cells indicated that a C18-steroid (estradiol or 3-deoxyestradiol) backbone and a spiro-delta-lactone (six-member ring) are important for a strong inhibitory activity. Moreover, the presence of a dimethyl group at the alpha-position of the lactone carbonyl increases the selectivity of the inhibitor toward 17 beta-HSD5. Compound 26, a 3-deoxyestradiol derivative with a dimethylated spiro-delta-lactone at position 17, possesses the most potent inhibitory activity for 17 beta-HSD5 (IC50 = 2.9 nM). It showed no binding affinity for estrogen, androgen, progestin and glucocorticoid receptors (ER, AR, PR and GR). A weak proliferative effect was, however, observed on ZR-75-1 (ER+) cells in culture at high concentration (1 mu M), but not at 0.03 mu M. Interestingly, no significant proliferative effect was detected on Shionogi (AR(+)) cells in culture in the presence of 0.1 and 1 mu M of lactone 26. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.020
• 作为产物：
  描述：

  (8R,9S,13S,14S,17S)-17-(4-hydroxybutyl)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol 在 Jones reagent 作用下， 以 丙酮 为溶剂， 以360 mg的产率得到(8R,9S,13S,14S,17S )-13-methyl-4',5',6,7,8,9,11,12,13,14,15,16-dodecahydrospiro [cyclopenta[a]phenanthrene17,2'pyran]-6'(3'H)-one
  参考文献：
  名称：

  Steroidal lactones as inhibitors of 17β-hydroxysteroid dehydrogenase type 5: Chemical synthesis, enzyme inhibitory activity, and assessment of estrogenic and androgenic activities

  摘要：

  Androgens are well known to play a predominant role in prostate cancer and other androgen-dependent diseases. To decrease the level of androgen testosterone in the prostate, we are interested in developing inhibitors of 17 beta-hydroxysteroid dehydrogenase type 5 (17 beta-HSD5). This enzyme expressed in the prostate is one of the two enzymes able to convert 4-androstene-3,17-dione into testosterone. From a screening study, it was found that a series of steroid derivatives bearing a lactone on D-ring demonstrated potent inhibition of 17 beta-HSD5 over-expressed in HEK-293 cells. The results of enzymatic assays using intact cells indicated that a C18-steroid (estradiol or 3-deoxyestradiol) backbone and a spiro-delta-lactone (six-member ring) are important for a strong inhibitory activity. Moreover, the presence of a dimethyl group at the alpha-position of the lactone carbonyl increases the selectivity of the inhibitor toward 17 beta-HSD5. Compound 26, a 3-deoxyestradiol derivative with a dimethylated spiro-delta-lactone at position 17, possesses the most potent inhibitory activity for 17 beta-HSD5 (IC50 = 2.9 nM). It showed no binding affinity for estrogen, androgen, progestin and glucocorticoid receptors (ER, AR, PR and GR). A weak proliferative effect was, however, observed on ZR-75-1 (ER+) cells in culture at high concentration (1 mu M), but not at 0.03 mu M. Interestingly, no significant proliferative effect was detected on Shionogi (AR(+)) cells in culture in the presence of 0.1 and 1 mu M of lactone 26. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.020