methyl (2Z)-2-[(benzyloxy)carbonyl]amino-3-(4-bromo-3-methylphenyl)acrylate | 905281-17-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl (2Z)-2-[(benzyloxy)carbonyl]amino-3-(4-bromo-3-methylphenyl)acrylate
• 英文别名: methyl (Z)-3-(4-bromo-3-methylphenyl)-2-(phenylmethoxycarbonylamino)prop-2-enoate
• CAS: 905281-17-6
• 化学式: C₁₉H₁₈BrNO₄
• 分子量: 404.26
• InChiKey: NQLZXZMAPNZFST-BOPFTXTBSA-N

物化性质

• 沸点：
  522.0±50.0 °C(Predicted)
• 密度：
  1.400±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2Z)-2-[(benzyloxy)carbonyl]amino-3-(4-bromo-3-methylphenyl)acrylate 在 乙酸铵 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium periodate 、 (Z,Z)-cycloocta-1,5-diene(R,R-1,2-bis(2,5-diethylphospholanyl)benzene)rhodium(I) tetrafluoroborate 、 O-(dicyclohexylphosphino)biphenyl 、 氢气 、 palladium diacetate 、 L-Selectride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， -78.0~80.0 ℃ 、344.74 kPa 条件下， 反应 72.67h， 生成 methyl (2S)-2-[(benzyloxy)carbonyl]amino-3-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-3-methylphenyl]propanoate
  参考文献：
  名称：

  Potent Benzimidazole Sulfonamide Protein Tyrosine Phosphatase 1B Inhibitors Containing the Heterocyclic (S)-Isothiazolidinone Phosphotyrosine Mimetic

  摘要：

  Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine ( pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 angstrom resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole. The ortho substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme inhibitors of PTP1B that also displayed low caco-2 permeability and cellular activity in an insulin receptor (IR) phosphorylation assay and an Akt phosphorylation assay. The design, synthesis, and SAR of this novel series of benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented herein.

  DOI：

  10.1021/jm0600904
• 作为产物：
  描述：

  4-溴-3-甲基苯甲酸甲酯 在 锂硼氢 、 草酰氯 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 51.5h， 生成 methyl (2Z)-2-[(benzyloxy)carbonyl]amino-3-(4-bromo-3-methylphenyl)acrylate
  参考文献：
  名称：

  Potent Benzimidazole Sulfonamide Protein Tyrosine Phosphatase 1B Inhibitors Containing the Heterocyclic (S)-Isothiazolidinone Phosphotyrosine Mimetic

  摘要：

  Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine ( pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 angstrom resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole. The ortho substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme inhibitors of PTP1B that also displayed low caco-2 permeability and cellular activity in an insulin receptor (IR) phosphorylation assay and an Akt phosphorylation assay. The design, synthesis, and SAR of this novel series of benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented herein.

  DOI：

  10.1021/jm0600904