(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(pent-2-yn-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione | 1338324-55-2

• 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: (6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(pent-2-yn-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione
• 英文别名: (6alpha,8alpha)-6-(Pent-2-Yn-1-Yloxy)androsta-1,4-Diene-3,17-Dione；(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-pent-2-ynoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 1338324-55-2
• 化学式: C₂₄H₃₀O₃
• 分子量: 366.5
• InChiKey: VZGAHAQWKVTWEF-RAPVPNNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-戊炔-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71%的产率得到(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(pent-2-yn-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-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

文献信息

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

  公开号：EP2556082B1

  公开（公告）日：2017-02-22
• 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.
• 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.