1,5-diphenyl-6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one | 111423-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1,5-diphenyl-6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
• 英文别名: 1,5-diphenyl-6-sulfanylidene-7H-pyrazolo[3,4-d]pyrimidin-4-one
• CAS: 111423-01-9
• 化学式: C₁₇H₁₂N₄OS
• 分子量: 320.374
• InChiKey: BSNYRTRWEJPYKR-UHFFFAOYSA-N

物化性质

• 熔点：
  >280 °C(Solv: N,N-dimethylformamide (68-12-2); water (7732-18-5))
• 沸点：
  513.9±42.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,5-diphenyl-6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 在 吡啶 、 N-氯代丁二酰亚胺 、 硫酸 、 碘 作用下， 以 乙醇 、 水 为溶剂， 反应 4.5h， 生成 1-Phenyl-1H-9-thia-1,2,4a,10-tetraaza-cyclopenta[b]fluoren-4-one
  参考文献：
  名称：

  Garin, Javier; Guillen, Carmen; Melendez, Enrique, Heterocycles, 1987, vol. 26, # 9, p. 2371 - 2379

  摘要：

  DOI：
• 作为产物：
  描述：

  5-amino-N-[(4-chlorophenyl)methylideneamino]-1-phenylpyrazole-4-carboxamide 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 78.0h， 生成 1,5-diphenyl-6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  El-Dean, A. M. Kamal; Geies, A. A., Journal of Chemical Research, Miniprint, 1997, # 10, p. 2255 - 2269

  摘要：

  DOI：

文献信息

• Design and Synthesis of Novel Thioethers Derived from 1,5-Diphenyl-6- thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones as Antiangiogenic Agents
  作者：Ahmed Malki、Doaa A.E Issa、Rasha Y. Elbayaa、Hayam M.A. Ashour

  DOI：10.2174/1570180815666180518112321

  日期：2018.11.29

  In attempts to discover new antiangiogenic entities, a novel series of thioethers derived from 6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidine-4(5H)ones was considered and designed. </P><P> Methods: Virtual screening was carried out through docking of the compounds into the vascular endothelial growth factor and matrix metalloproteinase-9 binding sites. Molecular docking studies were performed using Lamarckian Genetic Algorithm. Compounds possessing lowest ligandprotein pairwise interaction energies were synthesized and screened for their antiproliferative activities against five cancer cell lines namely MHCC97H (liver), MDA-MB 231 (Breast), Colo205 (Colon), A549 (lung), A498 (kidney) and IC50 values were determined for the most potent compounds. Additionally, they were tested for their antiangiogenic activities by testing their ability to inhibit Human Umbilical Vein Endothelial Cell (HUVEC), cord formation and migration in response to chemoattractant.

  Three compounds 2a, 2b and 5b showed significant antiangiogenic activities. The allyl thioether 2b was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Additionally, 2a, 2b and 5b, contrary to TNP-470, interfered with the migration of HUVECs in response to vascular endothelial growth factor rather than endothelial cells proliferation or cord formation. Compounds 2a, 2b and 5b were also investigated for their inhibitory effects on MMPs to investigate the relationship between their angiogenic activity and MMPs. Results revealed that compound 2b was the most effective MMP-9 inhibitor in this series. Additionally, compound 2b reduced the expression levels of VEGF and pERK1/2.

  Our results suggest that compound 2b is considered as a promising antiangiogenic agent by targeting VEGF and MMP-9.

  背景：为了发现新的抗血管生成物质，考虑和设计了一系列来源于6-硫代-6,7-二氢-1H-吡唑并[3,4-d]嘧啶-4(5H)酮的硫醚类化合物。 方法：通过将化合物对接到血管内皮生长因子和基质金属蛋白酶-9结合位点中进行虚拟筛选。采用Lamarckian遗传算法进行分子对接研究。合成具有最低配体-蛋白质配对相互作用能的化合物，并对其抗五种癌细胞系（肝脏MHCC97H、乳腺MDA-MB 231、结肠Colo205、肺A549、肾A498）增殖活性进行筛选，并确定其IC50值。此外，通过测试它们抑制人脐静脉内皮细胞（HUVEC）对化学引诱剂的细胞凝集和迁移能力来测试它们的抗血管生成活性。 结果：三种化合物2a、2b和5b表现出显著的抗血管生成活性。烯丙基硫醚2b是最活跃的化合物，其趋化活性数据几乎与阳性对照TNP-470相当。此外，与TNP-470相反，2a、2b和5b干扰HUVECs对血管内皮生长因子的迁移而不是内皮细胞增殖或细胞凝集。化合物2a、2b和5b也被调查其对MMPs的抑制作用，以研究它们的血管生成活性和MMPs之间的关系。结果表明，化合物2b是该系列中最有效的MMP-9抑制剂。此外，化合物2b减少了VEGF和pERK1/2的表达水平。 结论：我们的结果表明，化合物2b通过针对VEGF和MMP-9被认为是一种有前途的抗血管生成剂。
• Novel pyrazolo[3,4- d ]pyrimidines as dual Src-Abl inhibitors active against mutant form of Abl and the leukemia K-562 cell line
  作者：Samir M. El-Moghazy、Riham F. George、Essam Eldin A. Osman、Ahmed A. Elbatrawy、Miroslava Kissova、Ambra Colombo、Emmanuele Crespan、Giovanni Maga

  DOI：10.1016/j.ejmech.2016.07.034

  日期：2016.11

  Some novel 6-substituted pyrazolo[3,4-d]pyrimidines 4, 5, 6a-d, 7a-c, 8 and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines 9a-c, 10a-c, 11, 12a,b, 13a-c and 14 were synthesized and characterized by spectral and elemental analyses. They were screened for their biological activity in vitro against Abl and Src kinases. Compounds 7a and 7b revealed the highest activity against both wild and mutant Abl

  一些新颖的6-取代的吡唑并[3,4-d]嘧啶4、5、6a-d，7a-c，8和吡唑并[4,3-e] [1,2,4]三唑并[4,3-a合成了嘧啶9a-c，10a-c，11、12a，b，13a-c和14，并通过光谱和元素分析对其进行了表征。筛选它们在体外对Abl和Src激酶的生物学活性。化合物7a和7b对野生型和突变型Abl激酶以及Src激酶和白血病K-562细胞系均显示出最高的活性。它们可以被认为是进一步优化结构以获得更好活性的新选择。
• Shishoo, Chamanlal J.; Pathak, Urvish S.; Rathod, Ishwarsinh S., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 6, p. 684 - 695
  作者：Shishoo, Chamanlal J.、Pathak, Urvish S.、Rathod, Ishwarsinh S.、Jain, Kishore S.、Nargund, Laxmivenkatesh G.、Taranalli, Ashok D.、Patel, Hiren、Kumar, Vivek、Shirsath, Vikas S.

  DOI：——

  日期：——
• Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-<i>d</i>]pyrimidin-4(5<i>H</i>)-ones induced apoptosis in RKO colon cancer cells
  作者：Ahmed Malki、Hayam M. A. Ashour、Rasha Y. Elbayaa、Doaa A. E. Issa、Hassan A. Aziz、Xiaozhuo Chen

  DOI：10.3109/14756366.2015.1118686

  日期：2016.11.1

  Novel 1,5-diphenyl-6-substituted-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones were synthesized and characterized. All compounds were screened for their anti-proliferative activities in five different cancer cell lines. The results showed that compounds 7a and 7b comprising aminoguanidino or guanidino moiety at position 6 inhibited proliferation of RKO colon cancer cells with IC50 of 8 and 4 mu M, respectively. Compounds 7a and 7b induced apoptosis in RKO cells, which was confirmed by TUNEL and annexin V-FITC assays. Flow cytometric analysis indicated that compounds 7a and 7b arrested RKO cells in the G1 phase and the most active compound 7b increased levels of p53, p21, Bax, ERK1/2 and reduced levels of Bcl2 and Akt. Compound 7b also activates release of cytochrome c, which is consistent with activation of caspase-9. Additionally, compound 7b increased caspase-3 activity and cleaved PARP-1 in RKO cells. Collectively, these findings could establish a molecular basis for the development of new anti-cancer agents.
• Garin, Javier; Loscertales, Maria Pilar; Melendez, Enrique, Heterocycles, 1987, vol. 26, # 5, p. 1303 - 1312
  作者：Garin, Javier、Loscertales, Maria Pilar、Melendez, Enrique、Merchan, Francisco L.、Rodriguez, Ricardo、Tejero, Tomas

  DOI：——

  日期：——