(8R,9S,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]-phenanthrene-3,17(4H)-dione | 1150096-90-4

• 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,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]-phenanthrene-3,17(4H)-dione
• 英文别名: (8R,9S,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[α]phenanthrene-3,17(4H)-dione；(8R,9S,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,17-dione
• CAS: 1150096-90-4
• 化学式: C₁₉H₂₂N₂O₂
• 分子量: 310.396
• InChiKey: LXZUAHRFDGSEFH-KZQROQTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 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：
  36.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-癸炔-1-醇 、 (8R,9S,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]-phenanthrene-3,17(4H)-dione 在 silver trifluoromethanesulfonate 作用下， 反应 0.17h， 以30%的产率得到(6R,8R,9S,10R,13S,14S)-6-dec-2-ynoxy-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
  参考文献：
  名称：

  Novel Aromatase Inhibitors by Structure-Guided Design

  摘要：

  Human cytochrome P450 aromatase catalyzes with high specificity the synthesis of estrogens from androgens. Aromatase inhibitors (AIs) such as exemestane, 6-methylideneandrosta-1,4-diene-3,17-dione, are preeminent drugs for the treatment of estrogen-dependent breast cancer. The crystal structure of human placental aromatase has shown an androgen-specific active site. By utilization of the structural data, novel C6-substituted androsta-1,4-diene-3,17-dione inhibitors have been designed. Several of the C6-substituted 2-alkynyloxy compounds inhibit purified placental aromatase with IC50 values in the nanomolar range. Antiproliferation studies in a MCF-7 breast cancer cell line demonstrate that some of these compounds have EC50 values better than 1 nM, exceeding that for exemestane. X-ray structures of aromatase complexes of two potent compounds reveal that, per their design, the novel side groups protrude into the opening to the access channel unoccupied in the enzyme-substrate/exemestane complexes. The observed structure-activity relationship is borne out by the X-ray data. Structure-guided design permits utilization of the aromatase-specific interactions for the development of next generation AIs.

  DOI：

  10.1021/jm300930n
• 作为产物：
  描述：

  雄甾-1,4-二烯-3,17-二酮 在 N-溴代丁二酰亚胺(NBS) 、 3-[(3-羧基苯基)磺酰基]-1,2-三氮杂二烯-2-鎓-1-I去 、 锌 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 、 水 、 乙腈 为溶剂， 反应 78.33h， 生成 (8R,9S,10R,13S,14S)-4-diazo-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]-phenanthrene-3,17(4H)-dione
  参考文献：
  名称：

  Convenient method for the functionalization of the 4- and 6-positions of the androgen skeleton

  摘要：

  本文报道了甾体乙烯基重氮化合物的制备和反应活性，提供了一种便捷、对取代基容忍、化学选择性和立体选择性的方法，从共同前体合成4-和6-取代的雄激素类似物。在双铑催化下，O–H插入发生在卡宾位点，生成4-取代的甾体，而在银催化下，O–H插入发生在乙烯位点，生成6-取代的甾体。

  DOI：

  10.1039/c2cc31973j

文献信息

• SUBSTITUTED ANDROST-4-ENE DIONES
  申请人：Emory University

  公开号：EP2556082A2

  公开（公告）日：2013-02-13
• US8969327B2
  申请人：——

  公开号：US8969327B2

  公开（公告）日：2015-03-03
• [EN] SUBSTITUTED ANDROST-4-ENE DIONES<br/>[FR] ANDROST-4-ÈNE DIONES SUBSTITUÉES
  申请人：UNIV EMORY

  公开号：WO2011127232A2

  公开（公告）日：2011-10-13

  The disclosure relates to novel C4 and C6 substituted androst-4-ene diones as well as andros-1,4-diene diones and derivatives thereof, their process of preparation, pharmaceutical compounds containing them, and the use of said compounds for the treatment of hormone-related disorders in mammals. This includes hormone-dependent cancers, particularly those caused by elevated levels of estrogen and its intermediates. These compounds can also be used in the treatment of other hormone-related disorders, inluding benign prostatic hyperplasia, cardiovascular disease, and neurodegenerative disorders.
• Convenient method for the functionalization of the 4- and 6-positions of the androgen skeleton
  作者：Daniel Morton、Allison R. Dick、Debashis Ghosh、Huw M. L. Davies

  DOI：10.1039/c2cc31973j

  日期：——

  The preparation and reactivity of steroidal vinyldiazo compounds is reported, providing a convenient, substituent tolerant, chemo- and stereoselective entry into 4- and 6-substituted androgen analogues from a common precursor. Under dirhodium catalysis, O–H insertion occurs at the carbenoid site, leading to 4-substituted steroids, but under silver catalysis, O–H insertion occurs at the vinylogous position, leading to 6-substituted steroids.

  本文报道了甾体乙烯基重氮化合物的制备和反应活性，提供了一种便捷、对取代基容忍、化学选择性和立体选择性的方法，从共同前体合成4-和6-取代的雄激素类似物。在双铑催化下，O–H插入发生在卡宾位点，生成4-取代的甾体，而在银催化下，O–H插入发生在乙烯位点，生成6-取代的甾体。
• Novel Aromatase Inhibitors by Structure-Guided Design
  作者：Debashis Ghosh、Jessica Lo、Daniel Morton、Damien Valette、Jingle Xi、Jennifer Griswold、Susan Hubbell、Chinaza Egbuta、Wenhua Jiang、Jing An、Huw M. L. Davies

  DOI：10.1021/jm300930n

  日期：2012.10.11

  Human cytochrome P450 aromatase catalyzes with high specificity the synthesis of estrogens from androgens. Aromatase inhibitors (AIs) such as exemestane, 6-methylideneandrosta-1,4-diene-3,17-dione, are preeminent drugs for the treatment of estrogen-dependent breast cancer. The crystal structure of human placental aromatase has shown an androgen-specific active site. By utilization of the structural data, novel C6-substituted androsta-1,4-diene-3,17-dione inhibitors have been designed. Several of the C6-substituted 2-alkynyloxy compounds inhibit purified placental aromatase with IC50 values in the nanomolar range. Antiproliferation studies in a MCF-7 breast cancer cell line demonstrate that some of these compounds have EC50 values better than 1 nM, exceeding that for exemestane. X-ray structures of aromatase complexes of two potent compounds reveal that, per their design, the novel side groups protrude into the opening to the access channel unoccupied in the enzyme-substrate/exemestane complexes. The observed structure-activity relationship is borne out by the X-ray data. Structure-guided design permits utilization of the aromatase-specific interactions for the development of next generation AIs.