methyl 3-(4-[3-(4-aminophenyl)ureido]phenylaminomethyl)benzoate | 1392278-33-9

• 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: methyl 3-(4-[3-(4-aminophenyl)ureido]phenylaminomethyl)benzoate
• 英文别名: Methyl 3-[[4-[(4-aminophenyl)carbamoylamino]anilino]methyl]benzoate
• CAS: 1392278-33-9
• 化学式: C₂₂H₂₂N₄O₃
• 分子量: 390.442
• InChiKey: BEZPQSLMWNWGNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  106
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-[3-(4-aminophenyl)ureido]phenylaminomethyl)benzoate 、 在 4-二甲氨基吡啶 、 二异丙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 以43%的产率得到methyl 3-[[4-[[4-[6-[6-[4-[(3aR,4S,6aS)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]butanoylamino]hexanoylamino]hexanoylamino]phenyl]carbamoylamino]anilino]methyl]benzoate
  参考文献：
  名称：

  Discovery of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives as non-peptidic selective SUMO-sentrin specific protease (SENP)1 inhibitors

  摘要：

  We developed 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivative 4 (GN6958) as a non-peptidic selective SUMO-sentrin specific protease (SENP) 1 protease inhibitor based on the hypoxia inducible factor (HIF)-1 alpha inhibitor 1 (GN6767). The direct interaction of compound 1 with SENP1 protein in cells was observed by the pull-down experiments using the biotin-tagged compound 2 coated on the streptavidin affinity column. Among the various 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives tested, compounds 3 and 4 suppressed HIF-1 alpha accumulation in a concentration-dependent manner without affecting the expression level of tubulin protein in HeLa cells. Both compounds inhibited SENP1 protease activity in a concentration-dependent manner, and compound 4 exhibited more potent inhibition than compound 3. Compound 4 exhibited selective inhibition against SENP1 protease activity without inhibiting other protease enzyme activities in vitro. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.084
• 作为产物：
  描述：

  1,3-双(4-硝基苯基)脲 在 5%-palladium/activated carbon 、 氢气 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 methyl 3-(4-[3-(4-aminophenyl)ureido]phenylaminomethyl)benzoate
  参考文献：
  名称：

  Discovery of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives as non-peptidic selective SUMO-sentrin specific protease (SENP)1 inhibitors

  摘要：

  We developed 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivative 4 (GN6958) as a non-peptidic selective SUMO-sentrin specific protease (SENP) 1 protease inhibitor based on the hypoxia inducible factor (HIF)-1 alpha inhibitor 1 (GN6767). The direct interaction of compound 1 with SENP1 protein in cells was observed by the pull-down experiments using the biotin-tagged compound 2 coated on the streptavidin affinity column. Among the various 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives tested, compounds 3 and 4 suppressed HIF-1 alpha accumulation in a concentration-dependent manner without affecting the expression level of tubulin protein in HeLa cells. Both compounds inhibited SENP1 protease activity in a concentration-dependent manner, and compound 4 exhibited more potent inhibition than compound 3. Compound 4 exhibited selective inhibition against SENP1 protease activity without inhibiting other protease enzyme activities in vitro. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.084

文献信息

• Discovery of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives as non-peptidic selective SUMO-sentrin specific protease (SENP)1 inhibitors
  作者：Masaharu Uno、Yosuke Koma、Hyun Seung Ban、Hiroyuki Nakamura

  DOI：10.1016/j.bmcl.2012.06.084

  日期：2012.8

  We developed 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivative 4 (GN6958) as a non-peptidic selective SUMO-sentrin specific protease (SENP) 1 protease inhibitor based on the hypoxia inducible factor (HIF)-1 alpha inhibitor 1 (GN6767). The direct interaction of compound 1 with SENP1 protein in cells was observed by the pull-down experiments using the biotin-tagged compound 2 coated on the streptavidin affinity column. Among the various 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives tested, compounds 3 and 4 suppressed HIF-1 alpha accumulation in a concentration-dependent manner without affecting the expression level of tubulin protein in HeLa cells. Both compounds inhibited SENP1 protease activity in a concentration-dependent manner, and compound 4 exhibited more potent inhibition than compound 3. Compound 4 exhibited selective inhibition against SENP1 protease activity without inhibiting other protease enzyme activities in vitro. (c) 2012 Elsevier Ltd. All rights reserved.