Triethyl-[(3aR,4S,7aS)-1-((R)-3-iodo-1-methyl-propyl)-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-4-yloxy]-silane | 250384-86-2

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: Triethyl-[(3aR,4S,7aS)-1-((R)-3-iodo-1-methyl-propyl)-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-4-yloxy]-silane
• 英文别名: [(3aR,4S,7aS)-1-[(2R)-4-iodobutan-2-yl]-7a-methyl-3,3a,4,5,6,7-hexahydroinden-4-yl]oxy-triethylsilane
• CAS: 250384-86-2
• 化学式: C₂₀H₃₇IOSi
• 分子量: 448.503
• InChiKey: DMGAKZXGFNZDKG-BTHPGYMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.97
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  Triethyl-[(3aR,4S,7aS)-1-((R)-3-iodo-1-methyl-propyl)-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-4-yloxy]-silane 在 Oxone 、 重铬酸吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 17.0h， 生成 (3aR,7aS)-1-[(2R)-4-tert-butylsulfonylbutan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one
  参考文献：
  名称：

  概念上新的砜类似物的激素1alpha，25-dihydroxyvitamin D（3）：合成和初步生物学评估。

  摘要：

  合成了一个概念上新的系列维生素D（3）-样非氟化和氟化16烯侧链叔丁基砜3-7。即使激素1alpha，25-dihydroxyvitamin D（3）（1,1,25D（3））的这些新颖的C，D环侧链类似物都缺少一个末端OH基团，以前认为这对于高生物活性至关重要，它们具有高度的抗增殖作用，在某些情况下，其在体外具有转录活性，但在体内则希望是无血钙的。与天然1,25D（3）的25-OH基团的氢键供体功能相反，侧链砜基可能作为氢键受体与nVDR结合。

  DOI：

  10.1021/jm990267c
• 作为产物：
  描述：

  (R)-3-((3aR,4S,7aS)-7a-Methyl-4-triethylsilanyloxy-3a,4,5,6,7,7a-hexahydro-3H-inden-1-yl)-butan-1-ol 在 咪唑 、 碘 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以95%的产率得到Triethyl-[(3aR,4S,7aS)-1-((R)-3-iodo-1-methyl-propyl)-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-4-yloxy]-silane
  参考文献：
  名称：

  概念上新的砜类似物的激素1alpha，25-dihydroxyvitamin D（3）：合成和初步生物学评估。

  摘要：

  合成了一个概念上新的系列维生素D（3）-样非氟化和氟化16烯侧链叔丁基砜3-7。即使激素1alpha，25-dihydroxyvitamin D（3）（1,1,25D（3））的这些新颖的C，D环侧链类似物都缺少一个末端OH基团，以前认为这对于高生物活性至关重要，它们具有高度的抗增殖作用，在某些情况下，其在体外具有转录活性，但在体内则希望是无血钙的。与天然1,25D（3）的25-OH基团的氢键供体功能相反，侧链砜基可能作为氢键受体与nVDR结合。

  DOI：

  10.1021/jm990267c

文献信息

• Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃:  Synthesis and Biological Testing
  作者：Gary H. Posner、Bethany A. Halford、Sara Peleg、Patrick Dolan、Thomas W. Kensler

  DOI：10.1021/jm010560o

  日期：2002.4.1

  New chemical entities 16-ene-25-ketone 2b and the corresponding oxime 3b and oxime ether 4b, analogues of natural calcitriol (1), were rationally designed and synthesized on a milligram scale. Chemical introduction of the oxime ether functionality in analogue 4b was successful via direct oximation of an intact vitamin D conjugated triene system. Even though all three analogues are at least as antiproliferative in vitro as calcitriol (1) even at physiologically relevant low nanomolar concentrations, only side chain ketone 2b is more transcriptionally potent than calcitriol (1). Although oxime O-methyl ether 4b lacks the traditional side chain hydrogen bond-donating OH group of the natural hormone and lacks also the oxime-NOH group of analogue 3b, surprisingly, oxime ether 4b retains 20% of the transcriptional potency of natural calcitriol (1). In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1).
• [EN] 25-SO2-SUBSTITUTED ANALOGS OF 1ALPHA, 25-DIHYDROXYVITAMIN D3 (CALCITRIOL)<br/>[FR] ANALOGUES 25-SO2-SUBSITUTES DE LA 1 DOLLAR G(A),25-DIHYDROXYVITAMINE D3
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2004054968A3

  公开（公告）日：2004-10-21
• Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1α,25-dihydroxyvitamin D3: Chemical synthesis and biological evaluation
  作者：Aimee R. Usera、Patrick M. Dolan、Thomas W. Kensler、Gary H. Posner

  DOI：10.1016/j.bmc.2007.05.051

  日期：2007.8

  Novel fluorinated sulfone analogs of the hormone 1 alpha,25-dihydroxyvitamm D-3 have been designed and synthesized in order to study the biological effects of fluorine incorporation at the terminus of the C,D-ring side chain. Although biologically active 26,27-hexafluorinated 1 alpha,25-dihydroxyvitamin D-3 analogs have been synthesized previously, this investigation reports the first successful fluorinated series in which trifluoromethyl sulfone analogs present a favorable biological profile. This study shows that two new analogs featuring incorporation of a synthetically simple single trifluoromethyl sulfone group have significantly increased antiproliferative activity while causing desirably low in vivo calciuria relative to that of calcitriol. Incorporation of additional fluorines, as in a perfluorobutyl analog, results in a loss of antiproliferative activity. (c) 2007 Elsevier Ltd. All rights reserved.