(8R,9S,13S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,13-hexahydro-6H-cyclopenta[a]phenanthren-17(16H)-one | 872700-29-3

• 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,13S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,13-hexahydro-6H-cyclopenta[a]phenanthren-17(16H)-one
• 英文别名: (8R,9S,13S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,16-hexahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 872700-29-3
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: QKBOWGKFNXPADQ-QUJCMNEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲氧基雌素酮 生成 (8R,9S,13S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,13-hexahydro-6H-cyclopenta[a]phenanthren-17(16H)-one
  参考文献：
  名称：

  Structure-based design, synthesis and in vitro characterization of potent 17β-hydroxysteroid dehydrogenase type 1 inhibitors based on 2-substitutions of estrone and D-homo-estrone

  摘要：

  In search for specific drugs against steroid-dependent cancers we have developed a novel set of potent inhibitors of steroidogenic human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD 1). The X-ray structure of 17 beta-HSD 1 in complex with estradiol served as basis for the design of the inhibitors. 2-Substituted estrone and D-homo-estrone derivatives were synthesized and tested for 17 beta-HSD 1 inhibition. The best 17 beta-HSD 1 inhibitor, 2-phenethyl-D-homo-estrone, revealed an IC50 of 15 nM in vitro. The inhibitory potency of compounds is comparable or better to that of previously described inhibitors. An interaction within the cofactor binding site is not necessary to obtain this high binding affinity for substances developed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.113

文献信息

• New 2-substituted estra-1,3,5(10)-trien-17-ones as inhibitors of 17beta-hydroxy steroid dehydrogenase type 1
  申请人：Hillisch Alexander

  公开号：US20060009434A1

  公开（公告）日：2006-01-12

  The invention relates to new 2-substituted estra-1,3,5(10)-trien-17-ones of general formula I in which R 2 means a saturated or unsaturated C 1 -C 8 -alkyl group, a C 1 -C 5 -alkyloxy group, an aralkyl radical or alkylaryl radical, a radical —O—C n F m H o , whereby n=1, 2, 3, 4, 5 or 6, m≧1 and m+o=2n+1, or a group CH 2 XY, in which X stands for an oxygen atom and Y stands for an alkyl radical with 1 to 4 carbon atoms, as well as a halogen atom or a nitrile group, R 13 means a hydrogen atom or a methyl group, R 16 means a hydrogen atom or a fluorine atom, Z means an oxygen atom or a sulfur atom, R 3 and R 5 , in each case independently of one another, mean an α- or β-position hydrogen atom, R 4 and R 6 , in each case independently of one another, mean an α- or β-position hydrogen atom, a C 1 -C 5 -alkyl group, a C 1 -C 5 -alkyloxy group, a C 1 -C 5 -acyl group or a hydroxy group or an aralkyl radical or alkylaryl radical, R 3 and R 4 together mean an oxygen atom, R 5 and R 6 together mean an oxygen atom, R 7 and R 8 in each case mean a hydrogen atom or together a CH 2 group, as well as their pharmaceutically acceptable salts, their manufacture and use as medicaments for prophylaxis and therapy of estrogen-dependent diseases that can be influenced by the inhibition of 17β-hydroxy steroid dehydrogenase type 1.

  本发明涉及一般式I的新2-取代的酮类化合物，其中R2代表饱和或不饱和的C1-C8烷基基团，C1-C5烷氧基团，芳基烷基基团或烷基芳基基团，基团—O—CnFmHo，其中n=1、2、3、4、5或6，m≥1且m+o=2n+1，或基团CH2XY，其中X代表氧原子，Y代表具有1至4个碳原子的烷基基团，以及卤原子或腈基团，R13代表氢原子或甲基基团，R16代表氢原子或氟原子，Z代表氧原子或硫原子，R3和R5分别独立地表示α或β位的氢原子，R4和R6分别独立地表示α或β位的氢原子，C1-C5烷基基团，C1-C5烷氧基团，C1-C5酰基团，羟基或芳基烷基基团或烷基芳基基团，R3和R4一起表示氧原子，R5和R6一起表示氧原子，R7和R8分别表示氢原子或一起表示一个CH2基团，以及它们的药学上可接受的盐，它们的制备和用作预防和治疗由于17β-羟基类固醇脱氢酶类型1的抑制而可影响的雌激素依赖性疾病的药物。
• US7419972B2
  申请人：——

  公开号：US7419972B2

  公开（公告）日：2008-09-02
• Structure-based design, synthesis and in vitro characterization of potent 17β-hydroxysteroid dehydrogenase type 1 inhibitors based on 2-substitutions of estrone and D-homo-estrone
  作者：Gabriele Möller、Dominga Deluca、Christian Gege、Andrea Rosinus、Dorota Kowalik、Olaf Peters、Peter Droescher、Walter Elger、Jerzy Adamski、Alexander Hillisch

  DOI：10.1016/j.bmcl.2009.09.113

  日期：2009.12

  In search for specific drugs against steroid-dependent cancers we have developed a novel set of potent inhibitors of steroidogenic human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD 1). The X-ray structure of 17 beta-HSD 1 in complex with estradiol served as basis for the design of the inhibitors. 2-Substituted estrone and D-homo-estrone derivatives were synthesized and tested for 17 beta-HSD 1 inhibition. The best 17 beta-HSD 1 inhibitor, 2-phenethyl-D-homo-estrone, revealed an IC50 of 15 nM in vitro. The inhibitory potency of compounds is comparable or better to that of previously described inhibitors. An interaction within the cofactor binding site is not necessary to obtain this high binding affinity for substances developed. (C) 2009 Elsevier Ltd. All rights reserved.