1-(5-mercapto-[1,3,4]thiadiazol-2-yl)-3-phenylurea | 31199-89-0

• 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: 1-(5-mercapto-[1,3,4]thiadiazol-2-yl)-3-phenylurea
• 英文别名: 1-phenyl-3-(2-sulfanylidene-3H-1,3,4-thiadiazol-5-yl)urea
• CAS: 31199-89-0
• 化学式: C₉H₈N₄OS₂
• 分子量: 252.321
• InChiKey: FZQDTUCHCVJYHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(4-氯喹唑啉-7-基)氧丙基]吗啉 、 1-(5-mercapto-[1,3,4]thiadiazol-2-yl)-3-phenylurea 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以70%的产率得到1-{5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio][1,3,4]thiadiazol-2-yl}-3-phenylurea
  参考文献：
  名称：

  Discovery of the Novel Potent and Selective FLT3 Inhibitor 1-{5-[7-(3- Morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea and Its Anti-Acute Myeloid Leukemia (AML) Activitiesin Vitroandin Vivo

  摘要：

  Structure-activity relationship (SAR) studies of 2-(quinazolin-4-ylthio)thiazole derivatives, which are for optimizing the in vitro and in vivo antiacute myeloid leukemia (AML) activity of a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole (1), are described. SAR studies centering around the head (thiazole) and tails (6- and 7-positions) of the quinazoline moiety of 1 led to the discovery of a series of compounds that exhibited significantly dincreased potency against FLT3-driven AML MV4-11 cells. Preliminary in vivo assays were carried out on three highly active compounds, whose results showed that 1-{5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea (20c) had the highest in vivo activity. Further in vitro and in vivo anti-AML studies were then performed on 20c; in an MV4-11 xenograft mouse model, a once-daily dose of 20c at 100 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analysis were carried out to illustrate the mechanism of action of 20c.

  DOI：

  10.1021/jm300042x
• 作为产物：
  描述：

  异氰酸苯酯 、 2-氨基-5-巯基-1,3,4-噻二唑 以 二氯甲烷 为溶剂， 生成 1-(5-mercapto-[1,3,4]thiadiazol-2-yl)-3-phenylurea
  参考文献：
  名称：

  含有噻二唑脲的喹唑啉-4(3H)-1 类药物：抗增殖和抗血管生成活性的合成和评价

  摘要：

  设计、合成和生物学评估了一系列含有噻二唑脲的喹唑啉-4(3H)-one 试剂。化合物9f适度降低PC3细胞的增殖率（IC 50 = 17.7μ米)与索拉非尼相当（IC 50 = 17.3μ米）。当 HUVEC 细胞暴露于化合物9y (IC 50 = 6.1μ米). 为了测试化合物诱导细胞凋亡的潜力，使用膜联蛋白 V-FITC/碘化丙啶双染色测定。用9f处理 HUVEC 细胞后，它们经历了凋亡作用。大量的努力致力于收集跨 CAM 分析的综合数据。这些数据表明，9f适度抑制相应血管的生长。最后，蛋白质印迹的结果提出了一种作用机制，即化合物9f和9y抑制了 VEGFR-2 的磷酸化。

  DOI：

  10.1016/j.bioorg.2020.104553

文献信息

• Quinazolin-4(3H)-one based agents bearing thiadiazole-urea: Synthesis and evaluation of anti-proliferative and antiangiogenic activity
  作者：Aram Faraji、Rasoul Motahari、Zaman Hasanvand、Tayebeh Oghabi Bakhshaiesh、Mahsa Toolabi、Setareh Moghimi、Loghman Firoozpour、Mohammad Amin Boshagh、Roya Rahmani、Shima H.M.E. Ketabforoosh、Hamid Reza Bijanzadeh、Rezvan Esmaeili、Alireza Foroumadi

  DOI：10.1016/j.bioorg.2020.104553

  日期：2021.3

  A series of quinazolin-4(3H)-one based agents containing thiadiazole-urea were designed, synthesized, and biologically evaluated. The proliferation rate of PC3 cells was moderately reduced by compound 9f (IC50 = 17.7 μM)which was comparable with sorafenib (IC50 = 17.3 μM). There was also a significant reduction in the number of HUVEC cells, when they were exposed to compound 9y (IC50 = 6.1 μM). To

  设计、合成和生物学评估了一系列含有噻二唑脲的喹唑啉-4(3H)-one 试剂。化合物9f适度降低PC3细胞的增殖率（IC 50 = 17.7μ米)与索拉非尼相当（IC 50 = 17.3μ米）。当 HUVEC 细胞暴露于化合物9y (IC 50 = 6.1μ米). 为了测试化合物诱导细胞凋亡的潜力，使用膜联蛋白 V-FITC/碘化丙啶双染色测定。用9f处理 HUVEC 细胞后，它们经历了凋亡作用。大量的努力致力于收集跨 CAM 分析的综合数据。这些数据表明，9f适度抑制相应血管的生长。最后，蛋白质印迹的结果提出了一种作用机制，即化合物9f和9y抑制了 VEGFR-2 的磷酸化。
• Synthesis of a Series of Stromelysin-Selective Thiadiazole Urea Matrix Metalloproteinase Inhibitors
  作者：E. Jon Jacobsen、Mark A. Mitchell、Susan K. Hendges、Kenneth L. Belonga、Louis L. Skaletzky、Lindsay S. Stelzer、Thomas. J. Lindberg、Edward L. Fritzen、Heinrich J. Schostarez、Theresa J. O'Sullivan、Linda L. Maggiora、Christopher W. Stuchly、Alice L. Laborde、Marc F. Kubicek、Roger A. Poorman、Joan M. Beck、Henry R. Miller、Gary L. Petzold、Pam S. Scott、Scott E. Truesdell、Tanya L. Wallace、John W. Wilks、Christopher Fisher、Linda V. Goodman、Paul S. Kaytes、Stephen R. Ledbetter、Elaine A. Powers、Gabriel Vogeli、John E. Mott、Catherine M. Trepod、Douglas J. Staples、Eric T. Baldwin、Barry C. Finzel

  DOI：10.1021/jm9803222

  日期：1999.5.1

  The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an alpha-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin inhibitors, with K-i's between 0.3 and 1.0 mu M. The most effective analogues utilized an L-phenylalanine as the amino acid component. In particular, unsubstituted 46 had a K-i of 710 nM, while the p-fluoro analogue 52 displayed increased potency (100 nM). Stromelysin inhibition was further improved using a pentafluorophenylalanine substituent which resulted in 70, a 14 nM inhibitor. While gelatinase inhibition was generally poor, the use of 1-(2-pyridyl)piperazine as the amide component usually provided for enhanced activity, with 71 inhibiting gelatinase with a K-i of 770 nM. The combination of this heterocycle with a p-fluorophenylalanine substituent provided the only analogue, 69, with collagenase activity (13 mu M). The SAR for analogues described within this series can be rationalized through consideration of the X-ray structure recently attained for 70 complexed to stromelysin. Uniquely, this structure showed the inhibitor to be completely orientated on the left side of the enzyme cleft. These results suggest that thiadiazole urea heterocycles which incorporate a substituted phenylalanine can provide selective inhibitors of stromelysin. Careful selection of the amide substituent can also provide for analogues with modest gelatinase inhibition.
• Morphological changes of some pathogenic microbial strains induced by novel thiadiazole derivatives
  作者：M. G. El-Gazzar、N. H. Zaher、S. Y. El-Tablawy

  DOI：10.1007/s00044-013-0779-x

  日期：2014.4

  In the quest for potent antimicrobial agents, some new 1,3,4-thiadiazole derivatives (2-11) were synthesized from the starting compound (1) 5-amino-1,3,4-thiadiazole-2(3H)-thione, with an aim to evaluate their antimicrobial effect on different pathogenic organisms isolated from microbial-infected cancer patients who had not yet received their radiation dose, compared to reference antibiotics. The titled compounds 5, 6, 10, and 11 were found to possess comparable or more potent activity than the reference compounds amikacin and sulperazone. Compound 5 was the most distinctive derivative identified in the present study because of its remarkable antibacterial activity exhibited against the Gram +ve strains, it has been scanned under electron microscope to determine the morphological changes that has taken place in the bacterial cells of Bacillus cereus and non-irradiated and irradiated Staphylococcus aureus. MIC of compound 5 and/or gamma irradiation affected the morphology of the tested strains causing; membrane damage, deformity on the surface of some cells, disappearance of the septum, elongation of some cells, and shortening of others. It may be hoped that the present study will encourage efforts toward the development of novel antibacterial agents that could be better in terms of efficacy and safety.
• Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents
  作者：Mohammad M. Al-Sanea、Abdelrahman Hamdi、Simone Brogi、Samar S. Tawfik、Dina I. A. Othman、Mahmoud Elshal、Hidayat Ur Rahman、Della G. T. Parambi、Rehab M. Elbargisy、Samy Selim、Ehab M. Mostafa、Ahmed A. B. Mohamed

  DOI：10.1080/14756366.2022.2162511

  日期：2023.12.31
• New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and <i>in silico</i> study
  作者：Mohammad M. Al-Sanea、Abdelrahman Hamdi、Ahmed A. B. Mohamed、Hamed W. El-Shafey、Mahmoud Moustafa、Abdullah A. Elgazar、Wagdy M. Eldehna、Hidayat Ur Rahman、Della G. T. Parambi、Rehab M. Elbargisy、Samy Selim、Syed Nasir Abbas Bukhari、Omnia Magdy Hendawy、Samar S. Tawfik

  DOI：10.1080/14756366.2023.2166036

  日期：2023.12.31