KYS05045 | 839672-53-6

• 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: KYS05045
• 英文别名: Methyl 2-(2-(biphenyl-4-ylamino)-3-(5-(tert-butoxycarbonylamino)pentyl)-3,4-dihydroquinazolin-4-yl)acetate；methyl 2-[3-[5-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl]-2-(4-phenylanilino)-4H-quinazolin-4-yl]acetate
• CAS: 839672-53-6
• 化学式: C₃₃H₄₀N₄O₄
• 分子量: 556.705
• InChiKey: HMTFDPAABQXYFW-UHFFFAOYSA-N

物化性质

• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  KYS05045 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 [2-(Biphenyl-4-ylamino)-3-(5-tert-butoxycarbonylamino-pentyl)-3,4-dihydro-quinazolin-4-yl]-acetic acid
  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：

  (2E)-3-{2-[(triphenylphosphoranylidene)amino]phenyl}-propenoic acid methyl ester 以 乙腈 、 苯 为溶剂， 反应 5.0h， 生成 KYS05045
  参考文献：
  名称：

  Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers

  摘要：

  We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca2+ channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca2+ channels and N-type Ca2+ channels. Among them, 5b (KYS05044, IC50 = 0.56 +/- 0.10 muM) was identified as potent T-type Ca2+ channel blocker with in vitro selectivity profile at meaningful level (T/N-type, SI = >100). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.078

文献信息

• T-type Ca2+ channel blockers suppress the growth of human cancer cells
  作者：Jae Ho Heo、Han Na Seo、Yun Jeong Choe、Sujin Kim、Chun Rim Oh、Young Deuk Kim、Hyewhon Rhim、Dong Joon Choo、Jungahn Kim、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2008.06.034

  日期：2008.7

  In order to further clarify the role of T-type Ca2+ channels in cell proliferation, we have measured the growth inhibition of human cancer cells by using our potent T-type Ca2+ channel blockers. As a result, KYS05090, a most potent T-type Ca2+ channel blocker, was found to be as potent as doxorubicin against some human cancer cells without acute toxicity. Therefore, this letter provides the biological results that T-type calcium channel is important in regulating the important cellular phenotype transition leading to cell proliferation, and thus novel T-type Ca2+ channel blocker presents new prospects for cancer treatment. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and SAR Study of T-Type Calcium Channel Blockers. Part II
  作者：Yun Jeong Choe、Han Na Seo、Soo Yeon Jung、Hyewhon Rhim、Jungahn Kim、Dong Joon Choo、Jae Yeol Lee

  DOI：10.1002/ardp.200800079

  日期：2008.10

  3,4‐Dihydroquinazoline derivatives have been known to be the novel and potent T‐type calcium channel blockers. From a systematic variation of 3,4‐dihydroquinazoline derivative 5c (KYS05043), plausible SAR results were established. It was revealed that a 5‐(dimethylamino)pentylamino group at R1, a biphenyl group at R2, and a benzyl amido group at R3 in the 3,4‐dihydroquinazoline backbone are closely

  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。
• Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers
  作者：Hyewhon Rhim、Yong Sup Lee、Seong Jun Park、Bong Young Chung、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2004.10.078

  日期：2005.1

  We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca2+ channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca2+ channels and N-type Ca2+ channels. Among them, 5b (KYS05044, IC50 = 0.56 +/- 0.10 muM) was identified as potent T-type Ca2+ channel blocker with in vitro selectivity profile at meaningful level (T/N-type, SI = >100). (C) 2004 Elsevier Ltd. All rights reserved.