N-[1-(2-hydroxyethyl)piperidin-4-yl]-3-methoxy-1-methyl-4-oxo-5-(2-phenylethyl)pyrrolo[3,2-c]quinoline-2-carboxamide | 1396621-49-0

• 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: N-[1-(2-hydroxyethyl)piperidin-4-yl]-3-methoxy-1-methyl-4-oxo-5-(2-phenylethyl)pyrrolo[3,2-c]quinoline-2-carboxamide
• CAS: 1396621-49-0
• 化学式: C₂₉H₃₄N₄O₄
• 分子量: 502.613
• InChiKey: KBPDWOAVNQIYBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二羟基喹啉-3-甲酸乙酯 在 盐酸 、 三氟甲磺酸 、 sodium ethanolate 、 sodium acetate 、 potassium carbonate 、 1-羟基苯并三唑 、 苯甲醚 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 、 sodium t-butanolate 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 91.84h， 生成 N-[1-(2-hydroxyethyl)piperidin-4-yl]-3-methoxy-1-methyl-4-oxo-5-(2-phenylethyl)pyrrolo[3,2-c]quinoline-2-carboxamide
  参考文献：
  名称：

  Discovery of pyrrolo[3,2-c]quinoline-4-one derivatives as novel hedgehog signaling inhibitors

  摘要：

  The Hedgehog (Hh) signaling pathway plays a significant role in the regulation of cell growth and differentiation during embryonic development. Since activation of the Hh signaling pathway is implicated in several types of human cancers, inhibitors of this pathway could be promising anticancer agents. Using high throughput screening, thieno[3,2-c] quinoline-4-one derivative 9a was identified as a compound of interest with potent in vitro activity but poor metabolic stability. Our efforts focused on enhancement of in vitro inhibitory activity and metabolic stability, including core ring conversion and side chain optimization. This led to the discovery of pyrrolo[3,2-c] quinoline-4-one derivative 12b, which has a structure distinct from previously reported Hh signaling inhibitors. Compound 12b suppressed stromal Gli1 mRNA expression in a murine model and demonstrated antitumor activity in a murine medulloblastoma allograft model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.039

文献信息

• Discovery of pyrrolo[3,2-c]quinoline-4-one derivatives as novel hedgehog signaling inhibitors
  作者：Tomohiro Ohashi、Yuya Oguro、Toshio Tanaka、Zenyu Shiokawa、Sachio Shibata、Yoshihiko Sato、Hiroko Yamakawa、Harumi Hattori、Yukiko Yamamoto、Shigeru Kondo、Maki Miyamoto、Hideaki Tojo、Atsuo Baba、Satoshi Sasaki

  DOI：10.1016/j.bmc.2012.07.039

  日期：2012.9

  The Hedgehog (Hh) signaling pathway plays a significant role in the regulation of cell growth and differentiation during embryonic development. Since activation of the Hh signaling pathway is implicated in several types of human cancers, inhibitors of this pathway could be promising anticancer agents. Using high throughput screening, thieno[3,2-c] quinoline-4-one derivative 9a was identified as a compound of interest with potent in vitro activity but poor metabolic stability. Our efforts focused on enhancement of in vitro inhibitory activity and metabolic stability, including core ring conversion and side chain optimization. This led to the discovery of pyrrolo[3,2-c] quinoline-4-one derivative 12b, which has a structure distinct from previously reported Hh signaling inhibitors. Compound 12b suppressed stromal Gli1 mRNA expression in a murine model and demonstrated antitumor activity in a murine medulloblastoma allograft model. (C) 2012 Elsevier Ltd. All rights reserved.