13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one | 6544-68-9

• 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: 13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one
• 英文别名: 3-hydroxy-18-methyl-estra-1,3,5(10)-trien-17-one；3-hydroxy-18a-homoestra-1,3,5(10)-trien-17-one；3-Hydroxy-17-oxo-13β-ethyl-gonatrien-(1,3,5(10))；18a-methylestrone；18-Methyl-estrone；(8R,9S,13S,14S)-13-ethyl-3-hydroxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 6544-68-9
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: NQPGPSTYXRSFID-VXNCWWDNSA-N

物化性质

• 熔点：
  255 °C(Solv: acetone (67-64-1))
• 沸点：
  456.2±45.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于乙腈、二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one 在 硫酸 作用下， 以 溶剂黄146 为溶剂， 生成 Acetic acid (8R,9S,13S,14S)-3-acetoxy-13-ethyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-1-yl ester
  参考文献：
  名称：

  Rufer; Schröder; Gibian, Justus Liebigs Annalen der Chemie, 1971, vol. 752, p. 1 - 13

  摘要：

  DOI：
• 作为产物：
  描述：

  levonorgestrel 在 silver carbonate 、 lithium bromide 、 copper(ll) bromide 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 3.5h， 生成 13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  (17α,20E/Z)-iodovinyl- and 16α-iodo-18-homoestradiol derivatives: synthesis and evaluation for estrogen receptor imaging

  摘要：

  Three new I-125-radioiodinated estrogens featuring a 13 beta-ethyl instead of the natural 13-methyl group, i.e. 18-homoestradiols, were synthesized and evaluated as potential estrogen receptor imaging agents. The 16 alpha-iodo-18-methylestradiol and the I-125-labeled analog were synthesized from the corresponding 16 beta-bromo analog by the halogen-exchange method. The cis-bromohydrin precursor was obtained by bromination of an estrone enolacetate, followed by epimerization and reduction. The isomeric (17 alpha,20E/Z)-iodovinyl-18-methylestradiols were prepared via the vinyltin intermediates. Treatment of 18-methyl-17 alpha-ethynylestradiol with tri-n-butyltin hydride, in the presence of azobisisobutyronitrile as catalyst and heating at 90-100 degrees C afforded the (17 alpha,20E)-tri-n-butylstannyl isomer as the major product. Changing the catalyst for triethyl borane, at room temperature, mainly gave the 20Z-isomer. The nea I-125-labeled analogs were obtained from their corresponding tin intermediates upon treatment with [I-125]NaI in the presence of H2O2. The 16 alpha-[I-125]iodo- and isomeric (17 alpha,20E/Z)-[I-125]iodovinyl-18-methylestradiols were evaluated for estrogen receptor-mediated uterine uptake in immature female rats. Homologation of the C13-methyl group did improve the uterine uptake of the iodovinyl derivatives, but also increased blood retention, resulting in lower target uptake ratios. In the case of the 16 alpha-iodo analog uterine retention decreased upon C13-homologation. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00084-7

文献信息

• Discovery of novel steroidal histamine H 3 receptor antagonists/inverse agonists
  作者：Istvan Ledneczki、Pál Tapolcsányi、Eszter Gábor、János Éles、István Greiner、Éva Schmidt、Zsolt Némethy、Rita Soukupné Kedves、Ottilia Balázs、Viktor Román、György Lévay、Sándor Mahó

  DOI：10.1016/j.bmcl.2017.08.060

  日期：2017.10

  steroid-based histamine H3 receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H3 receptors

  从HTS运动中涌现，鉴定并表征了新型的基于类固醇的组胺H 3受体拮抗剂。结合命中化合物的结构部分以改善结合亲和力，从而产生化合物4作为前导分子。在由于二氨基类固醇衍生物的多用途修饰而导致的前导优化过程中，发现了几种对亚组胺H 3受体具有亲和力的体外有效化合物。通过调节碱度，成功减少了与鼠毒蕈碱受体的不利结合。化合物20在大鼠成虫模型中显示出显着的体内活性，并且将来可以用作药理学工具。
• C13-substituted estra-1,3,5,(10)-trien-3-yl sulfamates, methods of preparing same, and pharmaceutical compositions containing these compounds
  申请人：Schering AG

  公开号：US06583130B1

  公开（公告）日：2003-06-24

  The invention relates to new C13-substituted estra-1,3,5(10)-trien-3-yl sulfamates of general formula I, wherein R1 represents an acyl residue, oxycarbonyl residue, aminocarbonyl residue, sulfonyl residue, or aminosulfonyl residue, and R15 represents ethyl, methods of preparing same, and pharmaceutical compositions containing these compounds. The compounds of the invention of general formula I inhibit the activity of steroid sulfatase (EC 3.1.6.2) and do not exhibit any estrogenic effect.

  本发明涉及一种新的C13取代的Estra-1,3,5（10）-三烯-3-基磺酸酯，其一般式为I，其中R1代表酰基残基，氧羰基残基，氨羰基残基，磺酰基残基或氨基磺酰基残基，R15代表乙基，以及制备这些化合物的方法和含有这些化合物的药物组合物。本发明的一般式I化合物抑制类固醇磺酸酯酶（EC 3.1.6.2）的活性，不表现任何雌激素效应。
• WO2008/137599
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs—Part II
  作者：Pemmaraju N. Rao、James W. Cessac、James W. Boyd、Arthur D. Hanson、Jamshed Shah

  DOI：10.1016/j.steroids.2007.11.003

  日期：2008.2

  The syntheses and antimitotic activity of several novel 18a-homo-analogs of 2-methoxyestradiol are described. Structural modifications of the parent 2-methoxy-18a-homoestradiol include introduction of unsaturation in the D-ring and methylation of the 17-OH. Of seven analogs synthesized, one has demonstrated superior biological activities compared to 2-methoxyestradiol. The relationship between biological activity and the conformational preference of the 13-ethyl group as determined by computational analysis is discussed. (C) 2007 Elsevier Inc. All rights reserved.
• Preparative chemical methods for aromatization of 19-nor-Δ4-3-oxosteroids
  作者：Pemmaraju N. Rao、James W. Cessac、Hyun K. Kim

  DOI：10.1016/0039-128x(94)90017-5

  日期：1994.11

  Two preparative chemical methods for aromatization of 19-nor-Delta(4)-3-oxosteroids are described. The first method consists of an oxidative aromatization of 19-nor-Delta(4)-3-oxosteroids with iodine-eerie ammonium nitrate in methanol to give a mixture of 3-methoxy ring-A aromatized derivatives consisting of the desired product, the Delta(9,11) derivative, the 6-oxo derivative as well as some ring-A iodinated material. Conversion of this material to a mixture of the 3-methoxy ring-A aromatized derivative and its 6-oxo derivative was achieved by catalytic hydrogenation. Finally, reduction of the 6-oxo function with triethylsilane in trifluoroacetic acid gave the 3-methoxy-17-trifluoroacetate ring-A aromatized derivative as a single product. In the second method, reaction of 19-nor-Delta(4)-3-oxosteroids with copper(II) bromide in acetonitrile at room temperature resulted in aromatic steroids in a single step in excellent yields. The second method was used in the first practical chemical synthesis of a 6-dehydroestrogen from a 19-nor-Delta(4,6)-3-oxosteroid.