methyl (E)-3-[2-[(4-pyridin-2-ylphenyl)carbamoylamino]phenyl]prop-2-enoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl (E)-3-[2-[(4-pyridin-2-ylphenyl)carbamoylamino]phenyl]prop-2-enoate
• 化学式: C₂₂H₁₉N₃O₃
• 分子量: 373.411
• InChiKey: NYCHYXNKMNLQOB-SDNWHVSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-[2-[(4-pyridin-2-ylphenyl)carbamoylamino]phenyl]prop-2-enoate 在 triphenylphosphine dibromide 1:1 addition complex 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers

  摘要：

  The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.049
• 作为产物：
  描述：

  (E)-甲基3-(2-硝基苯基)丙烯酰基酯 在 叠氮磷酸二苯酯 、 氯化铵 、 三乙胺 、 锌 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 methyl (E)-3-[2-[(4-pyridin-2-ylphenyl)carbamoylamino]phenyl]prop-2-enoate
  参考文献：
  名称：

  In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers

  摘要：

  The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.049

文献信息

• [EN] NOVEL COMPOUND, METHOD FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITION COMPRISING SAME<br/>[FR] COMPOSÉ INÉDIT, SON PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE EN CONTENANT
  申请人：BORYUNG PHARM

  公开号：WO2014021591A2

  公开（公告）日：2014-02-06

  본 발명은 T-타입 칼슘 채널의 길항제로서 T-타입 칼슘채널의 기능과 관계된 장애와 질환의 치료 및 예방에 유용한 하이드로퀴나졸린 유도체에 관한 것이다. 본 발명은 또한 약학적으로 받아들여지는 이러한 화합물 유도체를 포함하는 조성물 및 이러한 화합물의 사용을 포함한다.
• In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers
  作者：Sun Jeong Jang、Heung Woo Choi、Doo Li Choi、Sehyeon Cho、Hong-Kun Rim、Hye-Eun Choi、Ki-Sun Kim、Minghua Huang、Hyewhon Rhim、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2013.10.049

  日期：2013.12

  The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved.