16α-(4-bromobutyl)-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)estra-1,3,5(10)-trien-17-one | 639460-54-1

• 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: 16α-(4-bromobutyl)-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)estra-1,3,5(10)-trien-17-one
• 英文别名: 3-tetrahydropyranyloxy-16β-methoxycarbonyl-16α-(4'-bromobutyl)-1,3,5(10)-estratrien-17-one；methyl (8R,9S,13S,14S,16S)-16-(4-bromobutyl)-13-methyl-3-(oxan-2-yloxy)-17-oxo-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthrene-16-carboxylate
• CAS: 639460-54-1
• 化学式: C₂₉H₃₉BrO₅
• 分子量: 547.53
• InChiKey: HYWVCLJTLXSVAM-CUUSNCISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  16α-(4-bromobutyl)-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)estra-1,3,5(10)-trien-17-one 在 sodium azide 作用下， 以 甲醇 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Design, synthesis and biological evaluation of estradiol–chlorambucil hybrids as anticancer agents

  摘要：

  A series of estradiol-chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16 alpha of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.053
• 作为产物：
  描述：

  3-tetrahydropyranyloxy-1,3,5(10)-estratrien-17-one 在 sodium hydroxide 、 potassium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 16α-(4-bromobutyl)-16β-(methoxycarbonyl)-3-(tetrahydropyran-2-yloxy)estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  17β-雌二醇铂（II）配合物的合成：对乳腺癌细胞系的生物学评估。

  摘要：

  描述了新型的17β-雌二醇连接的铂（II）配合物的合成。新分子在类固醇核的16α位置与烷基链连接，并带有16β-羟甲基侧链。它们由雌酮经五个化学步骤制得，总收率超过28％。在体外评估这些化合物对雌激素依赖性和非依赖性（ER +和ER-）人乳腺癌的生物学活性。掺有2-（2'-氨基乙基）吡啶配体的衍生物对细胞系表现出良好的活性，特别是当连接臂长为10个碳原子时。

  DOI：

  10.1016/j.bmcl.2003.09.011

文献信息

• Estrogen-linked platinum (II) complexes as anticancer agents
  申请人：Gervais Berube

  公开号：US20040006051A1

  公开（公告）日：2004-01-08

  1 wherein n may be 1, 2, 3, 4 or 5 when X is O, wherein n may be 2/3, 1, 4/3, 5/3, 2, 7/3, 8/3, 3, or 10/3 when X is C, wherein o may be 1, 2 or 3, wherein Y may be O or 17&bgr;-OH, wherein R 1 may be selected from the group consisting of H, a straight alkyl group of 1 to 5 carbon atoms, a branched alkyl group of 3 to 5 carbon atoms, wherein R 2 may be selected for the group consisting of H, a straight alkyl group of 1 to 4 carbon atoms, a branched alkyl group of 3 or 4 carbon atoms, F, Cl, Br, I, —CF 3 , —NO 2 , —OR 1 , —COR 1 and —CH 2 OH. These compounds possess anticancer activity against hormono-dependent breast, uterus as well as ovarian cancer.

  其中，当X为O时，n可以是1、2、3、4或5，当X为C时，n可以是2/3、1、4/3、5/3、2、7/3、8/3、3或10/3，o可以是1、2或3，Y可以是O或17β-OH，R1可以从H、1至5个碳原子的直链烷基或3至5个碳原子的支链烷基中选择，R2可以从H、1至4个碳原子的直链烷基或3或4个碳原子的支链烷基、F、Cl、Br、I、—CF3、—NO2、—OR1、—COR1和—CH2OH中选择。这些化合物对激素依赖性乳腺、子宫和卵巢癌具有抗癌活性。
• Synthesis and binding affinities of Re(I) and 99mTc(I)-containing 16α-substituted estradiol complexes: Models for potential breast cancer imaging agents
  作者：Liliang Huang、Hua Zhu、Yuanqing Zhang、Xiaoping Xu、Wei Cui、Guang Yang、Yu-Mei Shen

  DOI：10.1016/j.steroids.2010.05.006

  日期：2010.12

  synthesized tridentate metal tricarbonyl chelates substituted at the 16alpha-position of estradiol. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or elemental analysis. The rhenium complex 7b showed the highest ER binding affinity (RBA=25.7) among these compounds, so ligand 6b was selected to be labeled by the precursor [(99m)Tc(H(2)O)(3)(CO)(3)](+) to yield technetium(I)-99m complex

  为了开发用于雌激素受体（ER）阳性乳腺肿瘤的tech和imaging标记的成像剂，我们合成了在雌二醇的16alpha位取代的三齿三羰基金属螯合物。通过IR，（1）H NMR，（13）C NMR，HRMS或元素分析对它们的结构进行表征。these配合物7b在这些化合物中显示出最高的ER结合亲和力（RBA = 25.7），因此选择了配体6b标记为前体[（99m）Tc（H（2）O）（3）（CO）（3） ）]（+）生成tech（I）-99m配合物7b'，并具有良好的放射化学产率。相应地降低了相应的-（I）-99m配合物7b'的亲脂性，这可能有利于靶向体内的组织选择性。在体外6h内，复合物7b'在1mM组氨酸，1mM半胱氨酸，PBS和牛血清中的稳定性极佳。
• US7153844B2
  申请人：——

  公开号：US7153844B2

  公开（公告）日：2006-12-26
• Synthesis of 17β-estradiol platinum(II) complexes: biological evaluation on breast cancer cell lines
  作者：Caroline Descôteaux、Josée Provencher-Mandeville、Isabelle Mathieu、Valérie Perron、Sanat K Mandal、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.bmcl.2003.09.011

  日期：2003.11

  The synthesis of a novel series of 17beta-estradiol-linked platinum(II) complexes is described. The new molecules are linked with an alkyl chain at position 16alpha of the steroid nucleus and bear a 16beta-hydroxymethyl side chain. They are made from estrone in five chemical steps with an overall yield exceeding 28%. The biological activity of these compounds was evaluated in vitro on estrogen dependent

  描述了新型的17β-雌二醇连接的铂（II）配合物的合成。新分子在类固醇核的16α位置与烷基链连接，并带有16β-羟甲基侧链。它们由雌酮经五个化学步骤制得，总收率超过28％。在体外评估这些化合物对雌激素依赖性和非依赖性（ER +和ER-）人乳腺癌的生物学活性。掺有2-（2'-氨基乙基）吡啶配体的衍生物对细胞系表现出良好的活性，特别是当连接臂长为10个碳原子时。
• Design, synthesis and biological evaluation of estradiol–chlorambucil hybrids as anticancer agents
  作者：Atul Gupta、Pijus Saha、Caroline Descôteaux、Valérie Leblanc、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.bmcl.2010.01.053

  日期：2010.3

  A series of estradiol-chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16 alpha of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule. (C) 2010 Elsevier Ltd. All rights reserved.