阿美雌酮 | 10448-96-1

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 雌激素及孕激素类药
• 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
• 中文名称: 阿美雌酮
• 中文别名: 妊马雌酮；3-羟基-7a-甲基雌甾-1,3,5(10)-三烯-17-酮；甲基尹斯壮
• 英文名称: 7α-methylestrone
• 英文别名: 7α-Methyl-oestron；Almestrone；(7R,8R,9S,13S,14S)-3-hydroxy-7,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 10448-96-1
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: JUAJXSMWFOFDFC-MNHDCVOLSA-N

物化性质

• 熔点：
  231-233 °C
• 沸点：
  448.7±45.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  0
• 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

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	7α-methylestrone 3-methyl ether	10449-00-0	C20H26O2	298.425
  ——	16α-chloro-3-hydroxy-7α-methylestra-1,3,5(10)-trien-17-one	146016-45-7	C19H23ClO2	318.843
  ——	16β-bromo-3-hydroxy-7α-methylestra-1,3,5(10)-trien-17-one	146016-36-6	C19H23BrO2	363.294
  ——	7α-Methyl-16α-bromoestrone	146016-30-0	C19H23BrO2	363.294
  ——	7α-methylestrone acetate	36014-09-2	C21H26O3	326.436
  ——	2-fluoro-7α-methylestrone	151160-20-2	C19H23FO2	302.389
  ——	7α,17β-7-methyl-estra-1,3,5(10)-triene-3,17-diol	10448-97-2	C19H26O2	286.414
  ——	16β-bromo-7α-methylestra-1,3,5(10)-triene-3,17β-diol	146016-37-7	C19H25BrO2	365.31
  ——	(7R,8R,9S,13S,14S,17R)-17-ethynyl-4-fluoro-7,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol	151160-26-8	C21H25FO2	328.427
  ——	7α-methylestra-1,3,5(10),16-tetraene-3,17-diol diacetate	28838-19-9	C23H28O4	368.473

反应信息

• 作为反应物：
  描述：

  阿美雌酮 在 lithium aluminium tetrahydride 、 acetate buffer 、 硫酸 、 溴 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 溶剂黄146 为溶剂， 反应 4.25h， 生成 16α-bromo-7α-methylestra-1,3,5(10)-triene-3,17β-diol
  参考文献：
  名称：

  7.alpha.-Methyl- and 11.beta.-ethoxy-substitution of iodine-125-labeled [125I]16.alpha.-iodoestradiol: effect on estrogen receptor-mediated target tissue uptake

  摘要：

  The 7alpha-methyl and 11beta-ethoxy derivatives of 16alpha-[I-125]iodoestradiol were prepared via halogen exchange with I-125 of the corresponding 16beta-bromoestradiol precursors. The 16alpha-bromo derivatives were obtained via halogenation of the analogous 17-enol acetate, epimerization to the 16beta-isomer, and hydride reduction. Stereochemical assignments were based on high resolution H-1 NMR. To evaluate the effect of the nature and stereochemistry of the 16-halo substituent on the relative binding affinity for the estrogen receptor, the analogous 16-chloro derivatives were also prepared. The highest binding affinities were observed with the 7alpha-methyl-16alpha-haloestradiols, particularly the bromo and chloro derivatives while the 16alpha-iodo derivatives gave somewhat lower values. Both the 11beta-ethoxy and 7alpha-methyl-16alpha-[I-125]iodoestradiols localize in the uteri of immature female rats via a receptor-mediated process. Rapid blood clearance of the I-125-labeled 7alpha-methyl derivative results in lower I-125 uptake by the uterus as well as nontarget organs as compared to the 11beta-substituted estradiol analogs. However, uterus to blood and nontarget ratios are more favorable for the 7alpha-methyl-16alpha-[I-125]iodoestradiol as compared to the analogous 11beta-ethoxy derivatives suggesting that this compound substituted with I-125 may be useful for the in vivo imaging of estrogen receptor-rich breast tumors by single photon emission computerized tomography.

  DOI：

  10.1021/jm00054a011
• 作为产物：
  描述：

  4-estrene-7α-methyl-3,17-dione 在 氧气 、 copper dichloride 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以52%的产率得到阿美雌酮
  参考文献：
  名称：

  PROCESS FOR PRODUCTION OF STEROID COMPOUND

  摘要：

  公开号：

  EP1947107B1

文献信息

• Novel anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use
  申请人：——

  公开号：US20020032180A1

  公开（公告）日：2002-03-14

  Novel anti-estrogenic compounds are provided which are useful to treat a variety of disorders, particularly estrogen-dependent disorders. Preferred compounds have a 1,3,5-estratriene nucleus, and are substituted at the C-17 or C-11 position with a molecular moiety which renders the compounds effective to competitively block the binding of estrogen to its receptor. Particularly preferred compounds are 17-desoxy-1,3,5-estratrienes. Therapeutic methods and pharmaceutical compositions are provided as well.

  提供了新型抗雌激素化合物，这些化合物可用于治疗各种疾病，特别是依赖雌激素的疾病。优选的化合物具有1,3,5-雌三烯骨架，并在C-17或C-11位置上取代了一种分子基团，使这些化合物能够有效地竞争性地阻断雌激素与其受体的结合。特别优选的化合物是17-去氧-1,3,5-雌三烯。还提供了治疗方法和药物组合物。
• 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。
• Structure-activity relationships of estrogens. Effects of 14-dehydrogenation and axial methyl groups at C-7, C-9 and C-11
  作者：R Gabbard

  DOI：10.1016/0039-128x(83)90054-5

  日期：1983.6

  the estradiol-17 beta 3-methyl ether series. Uterotropic activities and inhibition of gonadotropin release did not parallel. The best compound for inhibiting gonadotropin release, as compared to uterotropic activity, was estrone. The "estrogen receptor" assay data correlated fairly well with uterotropic assay data, but only for compounds having free 3-hydroxyl groups; even so, some exceptions were noted

  在大鼠中评估了 30 种化合物的促子宫作用、抑制促性腺激素释放和 (3H) 雌二醇-17 β 从子宫细胞溶质制剂中的竞争性置换。7 α-甲基雌二醇-17 β 作为促子宫剂的活性是雌二醇-17 β 的 150%。Estradiol-17 beta 是最活跃的促性腺激素释放抑制剂。11 beta-Methylestradiol-17 beta 在从“雌激素受体”置换 (3H) estradiol-17 beta 方面具有 estradiol-17 beta 活性的 124%。在三种测定中的任何一种中，9 α-甲基都显着降低了雌激素的效力。14-脱氢改性仅在雌二醇-17 β 3-甲基醚系列中是有利的。促子宫活性和抑制促性腺激素释放不平行。抑制促性腺激素释放的最佳化合物，与促子宫活性相比，是雌酮。“雌激素受体”测定数据与亲子宫测定数据相当好相关，但仅针对具有游离3-羟基的化合物；即便如此，也注意到了一些例外情况。
• Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use
  申请人：——

  公开号：US20020032181A1

  公开（公告）日：2002-03-14

  Novel anti-estrogenic compounds are provided which are useful to treat a variety of disorders, particularly estrogen-dependent disorders. Preferred compounds have a 1,3,5-estratriene nucleus, and are substituted at the C-17 or C-11 position with a molecular moiety which renders the compounds effective to competitively block the binding of estrogen to its receptor. Particularly preferred compounds are 17-desoxy-1,3,5-estratrienes. Therapeutic methods and pharmaceutical compositions are provided as well.

  提供了一种新型的抗雌激素化合物，可用于治疗多种疾病，特别是雌激素依赖性疾病。首选化合物具有1,3,5-雌三烯核，且在C-17或C-11位置被取代为分子基团，使化合物能够有效地竞争性地阻止雌激素与其受体的结合。特别优选的化合物是17-去氧-1,3,5-雌三烯。同时提供了治疗方法和制药组合物。
• Diagnostic/therapeutic agents
  申请人：Klaveness Jo

  公开号：US20050002865A1

  公开（公告）日：2005-01-06

  Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

  可定位的诊断和/或治疗活性剂，例如超声对比剂，包括悬浮在水载体液中的报告物，该报告物包含含气体或生成气体的材料，该剂能够与目标形成至少两种结合对。