4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N′,N′-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline hydrochloride

• 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: 4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N′,N′-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline hydrochloride
• 英文别名: [3-(1,1'-biphenyl-4-yl)-2-(1-methyl-5-dimethylaminopentylamino)-3,4-dihydroquinazolin-4-yl]-N-benzylacetamide 2hydrochloride；KYS-05090S；KYS05090S；KYS05090；N-benzyl-2-[2-[5-(dimethylamino)pentyl-methylamino]-3-(4-phenylphenyl)-4H-quinazolin-4-yl]acetamide;hydrochloride
• 化学式: C₃₇H₄₃N₅O*2ClH
• 分子量: 646.703
• InChiKey: MXJWJZURGHCHGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.69
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N,N'-dimethylpentane-1,5-diamine 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 生成 4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N′,N′-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline hydrochloride
  参考文献：
  名称：

  In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.11.083

文献信息

• 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.
• 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.