甲基6-氨基-1,2,3,4-四氢-2-喹啉羧酸酯 | 112089-61-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甲基6-氨基-1,2,3,4-四氢-2-喹啉羧酸酯
• 英文名称: methyl 1,2,3,4-tetrahydro-6-aminoquinoline-2-carboxylate
• 英文别名: methyl 6-amino-1,2,3,4-tetrahydroquinoline-2-carboxylate
• CAS: 112089-61-9
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: DVIQIZQUBJXHQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲基6-氨基-1,2,3,4-四氢-2-喹啉羧酸酯 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 2-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-3-oxo-1-thioxo-1,2,3,3a,4,5-hexahydroimidazo[1,5-a]quinolin-7-methanesulfonamide
  参考文献：
  名称：

  Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists

  摘要：

  Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients. (c) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112196
• 作为产物：
  描述：

  methyl N-benzoyl-1,2,3,4-tetrahydroquinoline-2-carboxylate 在 盐酸 、 氯化亚砜 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 potassium nitrate 作用下， 以 甲醇 、 水 为溶剂， 反应 19.0h， 生成 甲基6-氨基-1,2,3,4-四氢-2-喹啉羧酸酯
  参考文献：
  名称：

  Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists

  摘要：

  Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients. (c) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112196

文献信息

• Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065
  作者：M. A. Warpehoski、I. Gebhard、R. C. Kelly、W. C. Krueger、L. H. Li、J. P. McGovren、M. D. Prairie、N. Wicnienski、W. Wierenga

  DOI：10.1021/jm00398a017

  日期：1988.3

  on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA.

  描述了以有效的抗肿瘤抗生素CC-1065（1）为模型的一系列新型螺环丙基化合物的合成，理化性质和生物学活性。这些合成类似物中的许多对鼠类肿瘤的疗效明显优于1。特别地，化合物27表现出高活性和效力。结构活性分析支持生物学作用的分子机制，涉及药物与DNA的疏水相互作用和酸催化的DNA烷基化。
• WARPEHOSKI, M. A.;GEBHARD, I.;KELLY, R. C.;KRUEGER, W. C.;LI, L. H.;MCGOV+, J. MED. CHEM., 31,(1988) N 3, 590-603
  作者：WARPEHOSKI, M. A.、GEBHARD, I.、KELLY, R. C.、KRUEGER, W. C.、LI, L. H.、MCGOV+

  DOI：——

  日期：——
• Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists
  作者：Xi Xu、Qianming Du、Ying Meng、Zhiyu Li、Hongxi Wu、Yan Li、Zhili Zhao、Raoling Ge、Xiaoyu Lu、Siqi Xue、Xijing Chen、Yong Yang、Jubo Wang、Jinlei Bian

  DOI：10.1016/j.ejmech.2020.112196

  日期：2020.4

  Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients. (c) 2020 Elsevier Masson SAS. All rights reserved.