6-nitro-2-(pyridin-3-yl)quinazolin-4(3H)-one | 1027034-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-nitro-2-(pyridin-3-yl)quinazolin-4(3H)-one
• 英文别名: 6-nitro-2-pyridin-3-yl-3H-quinazolin-4-one
• CAS: 1027034-81-6
• 化学式: C₁₃H₈N₄O₃
• 分子量: 268.232
• InChiKey: ZLPPGLWWAKRKLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-nitro-2-(pyridin-3-yl)quinazolin-4(3H)-one 在 palladium on activated charcoal 、 氢气 、 三氯氧磷 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 110.0 ℃ 、400.01 kPa 条件下， 反应 24.0h， 生成 acetic N-(4-((3-methoxyphenyl)amino)-2-(pyridin-3-yl)quinazolin-6-yl)acetimidic anhydride
  参考文献：
  名称：

  2,4,6-Substituted Quinazolines with Extraordinary Inhibitory Potency toward ABCG2

  摘要：

  Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent inhibitors of ABCG2. In this study, we identified novel inhibitors containing a 2,4,6-substituted quinazoline scaffold. Introduction of a 6-nitro function led to extraordinarily potent compounds that were highly selective for ABCG2 and also able to reverse the MDR toward the chemotherapeutic drugs SN-38 and mitoxantrone. The binding of substrate Hoechst 33342 and the two potent inhibitors 31 and 41 which differ in their mechanism of inhibition was rationalized using the recently published cryo-EM structures of ABCG2. For a better understanding of the interaction between the inhibitors and ABCG2, additional investigations regarding the ATPase activity, the interaction with Hoechst 33342, and with the conformational sensitive 5D3 antibody were carried out.

  DOI：

  10.1021/acs.jmedchem.8b01011
• 作为产物：
  描述：

  氯化烟碱盐酸盐 在 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 6-nitro-2-(pyridin-3-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014

文献信息

• Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities
  作者：Sung J. Lee、Yoshitaka Konishi、Dingwei T. Yu、Tamara A. Miskowski、Christopher M. Riviello、Orest T. Macina、Manton R. Frierson、Kigen Kondo、Masafumi Sugitani

  DOI：10.1021/jm00018a014

  日期：1995.9

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.
• 2,4,6-Substituted Quinazolines with Extraordinary Inhibitory Potency toward ABCG2
  作者：Michael K. Krapf、Jennifer Gallus、Vigneshwaran Namasivayam、Michael Wiese

  DOI：10.1021/acs.jmedchem.8b01011

  日期：2018.9.13

  Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent inhibitors of ABCG2. In this study, we identified novel inhibitors containing a 2,4,6-substituted quinazoline scaffold. Introduction of a 6-nitro function led to extraordinarily potent compounds that were highly selective for ABCG2 and also able to reverse the MDR toward the chemotherapeutic drugs SN-38 and mitoxantrone. The binding of substrate Hoechst 33342 and the two potent inhibitors 31 and 41 which differ in their mechanism of inhibition was rationalized using the recently published cryo-EM structures of ABCG2. For a better understanding of the interaction between the inhibitors and ABCG2, additional investigations regarding the ATPase activity, the interaction with Hoechst 33342, and with the conformational sensitive 5D3 antibody were carried out.