(S)-2-hydroxymethylpyrrolidin-1-ylacetonitrile | 115531-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-2-hydroxymethylpyrrolidin-1-ylacetonitrile
• 英文别名: (S)-2-(Hydroxymethyl)-1-pyrrolidineacetonitrile；2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]acetonitrile
• CAS: 115531-69-6
• 化学式: C₇H₁₂N₂O
• 分子量: 140.185
• InChiKey: SGQOSZCZBSODLV-ZETCQYMHSA-N

物化性质

• 沸点：
  263.0±15.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-hydroxymethylpyrrolidin-1-ylacetonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以63%的产率得到(S)-[1-(2-aminoethyl)pyrrolidin-2-yl]methanol
  参考文献：
  名称：

  Development of Nonsymmetrical 1,4-Disubstituted Anthraquinones That Are Potently Active against Cisplatin-Resistant Ovarian Cancer Cells

  摘要：

  A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.

  DOI：

  10.1021/jm050438f
• 作为产物：
  描述：

  L-脯氨醇 、 溴乙腈 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (S)-2-hydroxymethylpyrrolidin-1-ylacetonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of colchicine C-ring analogues tethered with aliphatic linkers suitable for prodrug derivatisation

  摘要：

  Colchicine was modified at the 10-OCH3 position of the C-ring by reaction with heterocyclic amines or commercially available amines to afford a library of target colchicinoids in high yields (62-99%). Molecular modeling revealed that the incorporation of the linker groups led to a reduction in entropy and therefore binding affinity when compared with colchicine. Some colchicinoids were shown to be equicytotoxic with colchicine when evaluated in the DLD-1 colon cancer cells and retained activity in resistant A2780AD or HeLa cells with mutant Class III beta-tubulin. Importantly, unlike colchicine, the analogues in this study are amenable for prodrug derivatisation and with potential for tumor-selective delivery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.104

文献信息

• 一种具有抗肿瘤活性的四氢吡啶并嘧啶类化合物
  申请人：江苏先声药业有限公司

  公开号：CN112047939B

  公开（公告）日：2023-05-02

  本发明提供了一种式(I)所示的四氢吡啶并嘧啶类化合物或其药学上可接受的盐，含有它们的药物组合物以及其在制备预防和/或治疗针对KRAS G12C突变肿瘤药物中的应用。
• Development of Nonsymmetrical 1,4-Disubstituted Anthraquinones That Are Potently Active against Cisplatin-Resistant Ovarian Cancer Cells
  作者：Klaus Pors、Jane A. Plumb、Robert Brown、Paul Teesdale-Spittle、Mark Searcey、Paul J. Smith、Laurence H. Patterson

  DOI：10.1021/jm050438f

  日期：2005.10.1

  A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.
• US4788212A
  申请人：——

  公开号：US4788212A

  公开（公告）日：1988-11-29
• Synthesis and biological evaluation of colchicine C-ring analogues tethered with aliphatic linkers suitable for prodrug derivatisation
  作者：Jérémie Fournier-Dit-Chabert、Victoria Vinader、Ana Rita Santos、Mariano Redondo-Horcajo、Aurore Dreneau、Ramkrishna Basak、Laura Cosentino、Gemma Marston、Hamdy Abdel-Rahman、Paul M. Loadman、Steven D. Shnyder、José Fernando Díaz、Isabel Barasoain、Robert A. Falconer、Klaus Pors

  DOI：10.1016/j.bmcl.2012.09.104

  日期：2012.12

  Colchicine was modified at the 10-OCH3 position of the C-ring by reaction with heterocyclic amines or commercially available amines to afford a library of target colchicinoids in high yields (62-99%). Molecular modeling revealed that the incorporation of the linker groups led to a reduction in entropy and therefore binding affinity when compared with colchicine. Some colchicinoids were shown to be equicytotoxic with colchicine when evaluated in the DLD-1 colon cancer cells and retained activity in resistant A2780AD or HeLa cells with mutant Class III beta-tubulin. Importantly, unlike colchicine, the analogues in this study are amenable for prodrug derivatisation and with potential for tumor-selective delivery. (C) 2012 Elsevier Ltd. All rights reserved.