5-[(2-苯基乙基)氨基]-1,3,4-噻二唑-2-硫醇 | 91129-85-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 5-[(2-苯基乙基)氨基]-1,3,4-噻二唑-2-硫醇
• 英文名称: 5-[(2-Phenylethyl)amino]-1,3,4-thiadiazole-2-thiol
• 英文别名: 5-(2-phenylethylamino)-3H-1,3,4-thiadiazole-2-thione
• CAS: 91129-85-0
• 化学式: C₁₀H₁₁N₃S₂
• mdl: MFCD03033838
• 分子量: 237.349
• InChiKey: CCTQEHDMZKCPPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  93.8
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-[(2-苯基乙基)氨基]-1,3,4-噻二唑-2-硫醇 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以85%的产率得到
  参考文献：
  名称：

  Sangal; Kumar, Journal of the Indian Chemical Society, 1988, vol. 65, # 11, p. 811 - 812

  摘要：

  DOI：
• 作为产物：
  描述：

  2-苯基乙基异硫代氰酸酯 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 5-[(2-苯基乙基)氨基]-1,3,4-噻二唑-2-硫醇
  参考文献：
  名称：

  Synthesis of a Series of Stromelysin-Selective Thiadiazole Urea Matrix Metalloproteinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm9803222

文献信息

• Sangal; Kumar, Journal of the Indian Chemical Society, 1988, vol. 65, # 11, p. 811 - 812
  作者：Sangal、Kumar

  DOI：——

  日期：——
• 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.