erythro-tert-butyl 2-(hydroxy(2-(4-methoxyphenyl)quinolin-4-yl)methyl)piperidine-1-carboxylate | 1384275-41-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: erythro-tert-butyl 2-(hydroxy(2-(4-methoxyphenyl)quinolin-4-yl)methyl)piperidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-[(R)-hydroxy-[2-(4-methoxyphenyl)quinolin-4-yl]methyl]piperidine-1-carboxylate
• CAS: 1384275-41-5
• 化学式: C₂₇H₃₂N₂O₄
• 分子量: 448.562
• InChiKey: HECXRUKMVODJTD-LOSJGSFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  71.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  erythro-tert-butyl 2-(hydroxy(2-(4-methoxyphenyl)quinolin-4-yl)methyl)piperidine-1-carboxylate 在 盐酸 作用下， 以 乙醇 为溶剂， 以0.6 g的产率得到(2-(4-methoxyphenyl)quinolin-4-yl)(piperidin-2-yl)methanol hydrochloride
  参考文献：
  名称：

  Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer

  摘要：

  Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.

  DOI：

  10.1021/jm300117u
• 作为产物：
  描述：

  2-(4-甲氧基苯基)-喹啉-4-羧酸 在 盐酸 、 platinum(IV) oxide 、 sodium tetrahydroborate 、 正丁基锂 、 硫酸 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 水 为溶剂， 反应 2.33h， 生成 erythro-tert-butyl 2-(hydroxy(2-(4-methoxyphenyl)quinolin-4-yl)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer

  摘要：

  Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.

  DOI：

  10.1021/jm300117u

文献信息

• [EN] IDENTIFICATION OF NSC23925 ISOMERS TO REVERSE MULTIDRUG RESISTANCE IN HUMAN CANCERS<br/>[FR] IDENTIFICATION D'ISOMÈRES NSC23925 POUR INVERSER LA RÉSISTANCE MULTIPLE AUX MÉDICAMENTS DANS DES CANCERS HUMAINS
  申请人：GEN HOSPITAL CORP

  公开号：WO2013126664A1

  公开（公告）日：2013-08-29

  This disclosure features optically active stereoisomers of (2-(4-methoxy)quinolin-4-yl)(piperidin-2-yl)methanol that reduce drug resistance, compositions containing the same, and methods of using and preparing the same.

  本公开涉及具有光学活性的立体异构体(2-(4-甲氧基)喹啉-4-基)(哌啶-2-基)甲醇，可降低药物耐药性，包含相同的组合物，以及使用和制备相同的方法。
• Identification of NSC23925 Isomers to Reverse Multidrug Resistance in Human Cancers
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US20140371165A1

  公开（公告）日：2014-12-18

  This disclosure features optically active stereoisomers of (2-(4-methoxy)quinolin-4-yl)(piperidin-2-yl)methanol that reduce drug resistance, compositions containing the same, and methods of using and preparing the same.

  本披露涉及光学活性对映异构体的(2-(4-甲氧基)喹啉-4-基)(哌啶-2-基)甲醇，它可以减少药物耐药性，以及包含它的组合物和使用和制备它的方法。
• Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer
  作者：Zhenfeng Duan、Xin Li、Haoxi Huang、Wei Yuan、Shao-Liang Zheng、Xianzhe Liu、Zhan Zhang、Edwin Choy、David Harmon、Henry Mankin、Francis Hornicek

  DOI：10.1021/jm300117u

  日期：2012.4.12

  Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.