KCP10043F

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: KCP10043F
• 英文别名: 2-(3-(4-Cyclohexylphenyl)-2-((3-(3,3-dimethylureido)propyl)(methyl)amino)-3,4-dihydroquinazolin-4-yl)-N-(4-fluorobenzyl)acetamide；2-[3-(4-cyclohexylphenyl)-2-[3-(dimethylcarbamoylamino)propyl-methylamino]-4H-quinazolin-4-yl]-N-[(4-fluorophenyl)methyl]acetamide
• 化学式: C₃₆H₄₅FN₆O₂
• 分子量: 612.791
• InChiKey: ONSKVAPFVGNDJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-nitrocinnamic acid 在 硫酸 、 叠氮磷酸二苯酯 、 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 氯化铵 、 三乙胺 、 锌 、 二溴三苯基膦 作用下， 以 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 34.0h， 生成 KCP10043F
  参考文献：
  名称：

  3,4-DIHYDROQUINAZOLINE DERIVATIVE AND COMBINATION COMPRISING THE SAME

  摘要：

  提供一种3,4-二氢喹啉衍生物或其药用可接受盐，以及含有该衍生物的组合物。该3,4-二氢喹啉衍生物或其药用可接受盐显示出阻断细胞内钙离子流入的活性，作为对癌细胞增殖和生长至关重要的次要信号，从而诱导癌细胞的细胞周期停滞，并最终增强现有抗癌药物的疗效。还提供了包括上述化合物和另一种抗癌药物的组合物。

  公开号：

  US20170081291A1

文献信息

• In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells
  作者：Joon Seok Byun、Joo Mi Sohn、Dong Gyu Leem、Byeongyeon Park、Ji Hye Nam、Dong Hyun Shin、Ji Sun Shin、Hyoung Ja Kim、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2015.12.010

  日期：2016.2

  As a result of our continuous research, new 3,4-dihydroquinazoline derivative containing ureido group, KCP10043F was synthesized and evaluated for T-type Ca2+ channel (Ca(v)3.1) blockade, cytotoxicity, and cell cycle arrest against human non-small cell lung (A549) cells. KCP10043F showed both weaker T-type Ca2+ channel blocking activity and less cytotoxicity against A549 cells than parent compound KYS05090S [4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N',N'-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline 2 hydrochloride], but it exhibited more potent G(1)-phase arrest than KYS05090S in A549 cells. This was found to be accompanied by the downregulations of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D2, cyclin D3, and cyclin E at the protein levels. However, p27(KIP1) as a CDK inhibitor was gradually upregulated at the protein levels and increased recruitment to CDK2, CDK4 and CDK6 after KCP10043F treatment. Based on the strong G(1)-phase cell cycle arrest of KCP10043F in A549 cells, the combination of KCP10043F with etoposide (or cisplatin) resulted in a synergistic cell death (combination index = 0.2-0.8) via the induction of apoptosis compared with either agent alone. Taken together with these overall results and the favorable in vitro ADME (absorption, distribution, metabolism, and excretion) profiles of KCP10043F, therefore, it could be used as a potential agent for the combination therapy on human lung cancer. (C) 2015 Elsevier Ltd. All rights reserved.
• 3,4-DIHYDROQUINAZOLINE DERIVATIVE AND COMBINATION COMPRISING THE SAME
  申请人：UNIVERSITY-INDUSTRY COOPERATION GROUP OF KYUNG HEE UNIVERSITY

  公开号：US20170081291A1

  公开（公告）日：2017-03-23

  A 3,4-dihydroquinazoline derivative or a pharmaceutically acceptable salt thereof and a composition containing the same are provided. The 3,4-dihydroquinazoline derivative or a pharmaceutically acceptable salt thereof show activities of blocking an intracellular influx of calcium ions acting as a secondary signal essential to the proliferation and growth of cancer cells, thereby inducing the cell cycle arrest of cancer cells, and eventually reinforcing the efficacy of existing anti-cancer drugs. A combination comprising the above compound and another anti-cancer drug is also provided.

  提供一种3,4-二氢喹啉衍生物或其药用可接受盐，以及含有该衍生物的组合物。该3,4-二氢喹啉衍生物或其药用可接受盐显示出阻断细胞内钙离子流入的活性，作为对癌细胞增殖和生长至关重要的次要信号，从而诱导癌细胞的细胞周期停滞，并最终增强现有抗癌药物的疗效。还提供了包括上述化合物和另一种抗癌药物的组合物。