t-butyl-N-[3-(N',N'-dimethylureido-propyl)]-N-methylcarbamate | 1581762-79-9

• 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
• 英文名称: t-butyl-N-[3-(N',N'-dimethylureido-propyl)]-N-methylcarbamate
• 英文别名: tert-butyl N-[3-(dimethylcarbamoylamino)propyl]-N-methylcarbamate
• CAS: 1581762-79-9
• 化学式: C₁₂H₂₅N₃O₃
• 分子量: 259.349
• InChiKey: VGLRZOOSMAHPPI-UHFFFAOYSA-N

物化性质

• 沸点：
  408.3±24.0 °C(Predicted)
• 密度：
  1.034±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  t-butyl-N-[3-(N',N'-dimethylureido-propyl)]-N-methylcarbamate 在 盐酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 4-[methoxycarbonylmethyl]-3-(4-cyclohexylphenyl)-2-[N-(N',N '-dimethylureidopropyl)-N-methyl]amino-3,4-dihydroquinazolin
  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
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.5h， 生成 t-butyl-N-[3-(N',N'-dimethylureido-propyl)]-N-methylcarbamate
  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

• Inhibition of cellular proliferation and induction of apoptosis in human lung adenocarcinoma A549 cells by T-type calcium channel antagonist
  作者：Doo Li Choi、Sun Jeong Jang、Sehyeon Cho、Hye-Eun Choi、Hong-Kun Rim、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2014.01.071

  日期：2014.3

  The anti-proliferative and apoptotic activities of new T-type calcium channel antagonist, 6e (BK10040) on human lung adenocarcinoma A549 cells were investigated. The MTT assay results indicated that BK10040 was cytotoxic against human lung adenocarcinoma (A549) and pancreatic cancer (MiaPaCa2) cells in a dose-dependent manner with IC50 of 2.25 and 0.93 mu M, respectively, which is ca. 2-fold more potent than lead compound KYS05090 despite of its decreased T-type calcium channel blockade. As a mode of action for cytotoxic effect of BK10040 on lung cancer (A549) cells, this cancer cell death was found to have the typical features of apoptosis, as evidenced by the accumulation of positive cells for annexin V. In addition, BK10040 triggered the activations of caspases 3 and 9, and the cleavages of poly (ADP-ribose) polymerase (PARP). Moreover, the treatment with z-VAD-fmk (a broad spectrum caspase inhibitor) significantly prevented BK10040-induced apoptosis. Based on these results, BK10040 may be used as a potential therapeutic agent for human lung cancer via the potent apoptotic activity. (C) 2014 Elsevier Ltd. All rights reserved.
• 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.
• US9969697B2
  申请人：——

  公开号：US9969697B2

  公开（公告）日：2018-05-15