N-benzyl-3-(biphenyl-4-yl)-2-[(5-N',N'-dibenzylaminopentyl)-N''-methylamino]-3,4-dihydroquinazolin-4-ylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl-3-(biphenyl-4-yl)-2-[(5-N',N'-dibenzylaminopentyl)-N''-methylamino]-3,4-dihydroquinazolin-4-ylacetamide
• 英文别名: N-benzyl-3-(4-biphenylyl)-2-[N-(5-N',N'-dibenzylaminopentyl)-N-methylamino]-3,4-dihydroquinazolin-4-ylacetamide；N-benzyl-2-[2-[5-(dibenzylamino)pentyl-methylamino]-3-(4-phenylphenyl)-4H-quinazolin-4-yl]acetamide
• 化学式: C₄₉H₅₁N₅O
• 分子量: 725.977
• InChiKey: NOPUAMGMEBAFNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  55
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyl-3-(biphenyl-4-yl)-2-[(5-N',N'-dibenzylaminopentyl)-N''-methylamino]-3,4-dihydroquinazolin-4-ylacetamide 在 1% Pd/C 、 氢气 作用下， 以 甲醇 为溶剂， 生成 4-(N-benzylacetamino)-3-(4-biphenylyl)-2-[N-(5-aminopentyl)-N-methylamino]-3,4-dihydroquinazoline
  参考文献：
  名称：

  T 型钙通道阻滞剂的合成和 SAR 研究。第二部分

  摘要：

  已知 3,4-二氢喹唑啉衍生物是新型有效的 T 型钙通道阻滞剂。根据 3,4-二氢喹唑啉衍生物 5c (KYS05043) 的系统变异，建立了合理的 SAR 结果。结果表明，3,4-二氢喹唑啉骨架中R1的5-(二甲氨基)戊氨基、R2的联苯基和R3的苄基氨基与通道选择性(T/N型)密切相关。以及基于 6k (KYS05090) 发现的效力。

  DOI：

  10.1002/ardp.200800079
• 作为产物：
  描述：

  methyl 3-(2-aminophenyl)acrylate 在 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 三乙胺 、 二溴三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 37.0h， 生成 N-benzyl-3-(biphenyl-4-yl)-2-[(5-N',N'-dibenzylaminopentyl)-N''-methylamino]-3,4-dihydroquinazolin-4-ylacetamide
  参考文献：
  名称：

  Anti-Cancer Activity of T-Type Calcium Channel Blocker In Vivo

  摘要：

  3,4-二氢喹唉1作为T型钙通道阻滞剂，在BALB/c-nu Slc裸鼠的A549异种移植模型中进行了体内评估，口服给药8毫克/千克体重显示出54%的肿瘤生长抑制作用，略低于多柔比星的68%活性。此外，还对该化合物对ICR小鼠的急性毒性进行了评估，得到了口服LD50值为1038毫克/千克体重。

  DOI：

  10.5012/bkcs.2010.31.11.3353

文献信息

• 3,4-DIHYDROQUINAZOLINE DERIVATIVES
  申请人：Lee Jae Yeol

  公开号：US20100120803A1

  公开（公告）日：2010-05-13

  The present invention relates to 3,4-dihydroquinazoline derivatives, a process of preparing them and a pharmaceutical composition including them. The 3,4-dihydroquinazoline derivatives of the present invention have excellent T-type calcium channel blocking effect and anti-cancer activity.

  本发明涉及3,4-二氢喹唑啉衍生物、其制备方法以及包括它们的药物组合物。本发明的3,4-二氢喹唑啉衍生物具有出色的T型钙通道阻滞效果和抗癌活性。
• Antitumor activity of 3,4-dihydroquinazoline dihydrochloride in A549 xenograft nude mice
  作者：Soo Yeon Jung、So Hyung Lee、Han Byul Kang、Hang Ah Park、Sun Ki Chang、Jungahn Kim、Dong Joon Choo、Chun Rim Oh、Young Deuk Kim、Ji Hyung Seo、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2010.09.020

  日期：2010.11

  In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1 center dot 2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1 center dot 2HCl has an oral bioavailability of 98% with LD(50) values of 693 mg/kg (po route) and 40.0 mg/kg (iv route) of body weight. In addition, its efficient scale-up synthetic method was developed. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of potent T-type calcium channel blocker
  作者：Han Na Seo、Ja Youn Choi、Yun Jeong Choe、Yoonjee Kim、Hyewhon Rhim、So Ha Lee、Jungahn Kim、Dong Jun Joo、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2007.08.070

  日期：2007.11

  The intensive SAR study of 3,.4-dihydroquinazoline series led to the most potent compound 10 (KYS05090: IC50 = 41 +/- 1 nM) against T-type calcium channel and its potency is nearly comparable to that of Kurtoxin. As a small organic molecule, this compound showed the highest blocking activity reported to date. (c) 2007 Elsevier Ltd. All rights reserved.
• In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor
  作者：Han Byul Kang、Hong-Kun Rim、Jin Yeong Park、Heung Woo Choi、Doo Li Choi、Ji-Hyung Seo、Kyung-Sook Chung、Geun Huh、Jungahn Kim、Dong Joon Choo、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2011.11.083

  日期：2012.1

  An extension of our previously reported 3.4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c(nu/nu) nude mice. The rate of tumor volume increment in mouse model with KY505090-treated group was remarkably slower than that of control group. With respect to tumor weight, it exhibited 60% and 67% tumor growth inhibition through oral administration of 1 and 5 mg/kg of bodyweight, respectively, compared to control and was more potent than paclitaxel (53%). In addition, KYS05090 (10 and 50 mg/kg, po) was found to have a marked analgesic effect in acetic acid-induced writhing test, whereas it did not show any effect on hot plate test. (C) 2011 Elsevier Ltd. All rights reserved.
• WO2008/136631
  申请人：——

  公开号：——

  公开（公告）日：——