2-[3-(4-methylphenyl)-5-(2-thienyl)-2-pyrazolin-1-yl]-3-methyl-4(3H)-quinazolinone | 1134193-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[3-(4-methylphenyl)-5-(2-thienyl)-2-pyrazolin-1-yl]-3-methyl-4(3H)-quinazolinone
• 英文别名: 3-Methyl-2-[5-(4-methylphenyl)-3-thiophen-2-yl-3,4-dihydropyrazol-2-yl]quinazolin-4-one
• CAS: 1134193-77-3
• 化学式: C₂₃H₂₀N₄OS
• 分子量: 400.504
• InChiKey: QVXMEQFRTCVWEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  76.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-[2-[1'-(4-methylphenyl)-3'-(2-thienyl)-2'-propenylidene]hydrazino]-3-methyl-4(3H)-quinazolinone 在 溶剂黄146 作用下， 反应 72.0h， 以94%的产率得到2-[3-(4-methylphenyl)-5-(2-thienyl)-2-pyrazolin-1-yl]-3-methyl-4(3H)-quinazolinone
  参考文献：
  名称：

  New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B selectivity

  摘要：

  A new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant, anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests, respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h, 4j-4n, and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However, none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Compounds 4i, 4k, 5e, 5i, and 5l were chosen for their ability to reversibly inhibit MAO-B and MAO-A and the availability of experimental inhibition data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Among the pyrazoline derivatives, it appears that the binding interactions for this class of compounds are mostly hydrophobic. All have potential edge-to-face hydrophobic interactions with F343, as well as pi-pi stacking with Y398 and other hydrophobic interactions with L171. Strong hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the reason why this compound shows selectivity toward the MAO-B isoform. The very high MAO-B selectivity for 4i can be also explained in terms of the distance between the FAD and the compound, which was greater in the complex of MAO-A-4i as compared to the corresponding MAO-B complex. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.068

文献信息

• New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B selectivity
  作者：Nesrin Gökhan-Kelekçi、Semra Koyunoğlu、Samiye Yabanoğlu、Kemal Yelekçi、Özen Özgen、Gülberk Uçar、Kevser Erol、Engin Kendi、Akgül Yeşilada

  DOI：10.1016/j.bmc.2008.11.068

  日期：2009.1

  A new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant, anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests, respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h, 4j-4n, and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However, none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Compounds 4i, 4k, 5e, 5i, and 5l were chosen for their ability to reversibly inhibit MAO-B and MAO-A and the availability of experimental inhibition data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Among the pyrazoline derivatives, it appears that the binding interactions for this class of compounds are mostly hydrophobic. All have potential edge-to-face hydrophobic interactions with F343, as well as pi-pi stacking with Y398 and other hydrophobic interactions with L171. Strong hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the reason why this compound shows selectivity toward the MAO-B isoform. The very high MAO-B selectivity for 4i can be also explained in terms of the distance between the FAD and the compound, which was greater in the complex of MAO-A-4i as compared to the corresponding MAO-B complex. (C) 2008 Elsevier Ltd. All rights reserved.