N-butyl-N-methyl-11-{3',17'β-dihydroxy-17'α-[3'-(tetrahydro-2'H-pyran-2'-yloxy)propynyl]-1',3',5'(10')-oestratrien-7'α-yl}-undecanamide | 269393-71-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: N-butyl-N-methyl-11-{3',17'β-dihydroxy-17'α-[3'-(tetrahydro-2'H-pyran-2'-yloxy)propynyl]-1',3',5'(10')-oestratrien-7'α-yl}-undecanamide
• 英文别名: N-butyl-11-[(7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-17-[3-(oxan-2-yloxy)prop-1-ynyl]-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-7-yl]-N-methylundecanamide
• CAS: 269393-71-7
• 化学式: C₄₂H₆₅NO₅
• 分子量: 663.982
• InChiKey: LMCOAVJIZGILIX-CFGDFMJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-butyl-N-methyl-11-{3',17'β-dihydroxy-17'α-[3'-(tetrahydro-2'H-pyran-2'-yloxy)propynyl]-1',3',5'(10')-oestratrien-7'α-yl}-undecanamide 在 palladium on activated charcoal 、 Lindlar's catalyst 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 64.0h， 以92%的产率得到N-butyl-N-methyl-11-{3',17'β-dihydroxy-17'α-[3'-(tetrahydro-2'H-pyran-2'-yloxy)propyl]-1',3',5'(10')-oestratrien-7'α-yl}-undecanamide
  参考文献：
  名称：

  N-Butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'α-pregna-1',3',5'(10')-trien-7'α-yl)-undecanamide: an inhibitor of type 2 17β-hydroxysteroid dehydrogenase that does not have oestrogenic or androgenic activity

  摘要：

  It is well known that 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) play a key role in the formation and inactivation, from circulating precursors, of several active androgens and oestrogens. These enzymes can thus regulate tumoural cell proliferation in androgen- and oestrogen-dependent cancers. Recently, we discovered that adding a spiro-gamma-lactone to the oestradiol nucleus results in a novel inhibitor of type 2 17 beta-HSD, an enzyme that catalyses the interconversions between 4-androstene-3,17-dione and testosterone, and between oestrone and oestradiol. This finding motivated our introducing the spiro-gamma-lactone moiety onto an anti-oestrogenic nucleus. The N-butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'alpha-pregna-1',3',5'(10')-trien-7'alpha-yl)-undecanamide (4) was then efficiently synthesized and its biological activity was assessed in vitro. Despite the presence of a bulky alkylamide side chain, the spiro-gamma-lactone function conserved its ability to inhibit type 2 17 beta-HSD (IC50 = 0.35 and 0.25 mu M, with and without side chain, respectively). Furthermore, the selective inhibition by lactone 4 toward type 2 17 beta-HSD (microsomal fraction of human placenta) was demonstrated by the absence of inhibitory activity toward type 1 17 beta-HSD (cytosolic fraction of human placenta). Cell proliferation assays indicated that compound 4 had no oestrogenic activity but did show anti-oestrogenic activity on ER+ cell line ZR-75-1. No androgenic activity could be detected when assayed on the AR(+) cell Line Shionogi either. Based on these facts, we report the synthesis of a new steroidal derivative, one that inhibits type 2 17 beta-HSD while possessing anti-oestrogenic activity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00124-0
• 作为产物：
  描述：

  3-benzoyloxy 7α-(11'-hydroxy undecyl) estra-1,3,5(10)-trien-17β-ol 在 正丁基锂 、 jones reagent 、 三正丁胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 丙酮 为溶剂， 反应 9.5h， 生成 N-butyl-N-methyl-11-{3',17'β-dihydroxy-17'α-[3'-(tetrahydro-2'H-pyran-2'-yloxy)propynyl]-1',3',5'(10')-oestratrien-7'α-yl}-undecanamide
  参考文献：
  名称：

  N-Butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'α-pregna-1',3',5'(10')-trien-7'α-yl)-undecanamide: an inhibitor of type 2 17β-hydroxysteroid dehydrogenase that does not have oestrogenic or androgenic activity

  摘要：

  It is well known that 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) play a key role in the formation and inactivation, from circulating precursors, of several active androgens and oestrogens. These enzymes can thus regulate tumoural cell proliferation in androgen- and oestrogen-dependent cancers. Recently, we discovered that adding a spiro-gamma-lactone to the oestradiol nucleus results in a novel inhibitor of type 2 17 beta-HSD, an enzyme that catalyses the interconversions between 4-androstene-3,17-dione and testosterone, and between oestrone and oestradiol. This finding motivated our introducing the spiro-gamma-lactone moiety onto an anti-oestrogenic nucleus. The N-butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'alpha-pregna-1',3',5'(10')-trien-7'alpha-yl)-undecanamide (4) was then efficiently synthesized and its biological activity was assessed in vitro. Despite the presence of a bulky alkylamide side chain, the spiro-gamma-lactone function conserved its ability to inhibit type 2 17 beta-HSD (IC50 = 0.35 and 0.25 mu M, with and without side chain, respectively). Furthermore, the selective inhibition by lactone 4 toward type 2 17 beta-HSD (microsomal fraction of human placenta) was demonstrated by the absence of inhibitory activity toward type 1 17 beta-HSD (cytosolic fraction of human placenta). Cell proliferation assays indicated that compound 4 had no oestrogenic activity but did show anti-oestrogenic activity on ER+ cell line ZR-75-1. No androgenic activity could be detected when assayed on the AR(+) cell Line Shionogi either. Based on these facts, we report the synthesis of a new steroidal derivative, one that inhibits type 2 17 beta-HSD while possessing anti-oestrogenic activity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00124-0