5-[2-(4-Chlorophenyl)ethylamino]-5-oxopentanoic acid | 646509-09-3

• 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: 5-[2-(4-Chlorophenyl)ethylamino]-5-oxopentanoic acid
• CAS: 646509-09-3
• 化学式: C₁₃H₁₆ClNO₃
• mdl: MFCD06065249
• 分子量: 269.728
• InChiKey: STRZUXJFGRPPIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  530.1±40.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  戊二酸酐 、 4-氯苯乙胺 以 乙腈 为溶剂， 反应 10.0h， 以86%的产率得到5-[2-(4-Chlorophenyl)ethylamino]-5-oxopentanoic acid
  参考文献：
  名称：

  Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D QSAR Studies of Phenethylamine Derivatives

  摘要：

  A series of 45 phenethylamine derivatives were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (ALR2, EC 1.1.1.21). Their IC50 values ranged from 400 muM to 24 muM. The binding modes of compounds at the active site of ALR2 were examined using flexible docking. The results indicated that phenethylamine derivatives nicely fit into the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of the compounds. The best prediction was obtained by CoMSIA combined with hydrophobic and hydrogen bond donor/acceptor field (q(2) = 0.557, r(2) = 0.934). A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking into account the CoMSIA field and the binding mode derived by FlexX docking. This rationally designed compound exhibits an ALR2 inhibition with an IC50 value of 7.4 muM, which compares favorably to that of a well-known ALR2 inhibitor, tolrestat (IC50 = 16 muM) and represents a potency approximately 240-fold higher than that of an original phenethylamine lead compound, YUA001.

  DOI：

  10.1021/jm0205346

文献信息

• Cyclohexyl-1, 4-diamine compounds
  申请人：Sundermann Corinna

  公开号：US20070112007A1

  公开（公告）日：2007-05-17

  Novel cyclohexyl-1,4-diamine compounds corresponding to formula I, processes for the production thereof, pharmaceutical compositions containing these compounds, methods of producing pharmaceutical compositions including these compounds and related methods of treating or inhibiting certain diseases or conditions.

  新型环己基-1,4-二胺化合物对应于式I，其生产方法，包含这些化合物的药物组合物，制备包含这些化合物的药物组合物的方法以及相关的治疗或抑制某些疾病或状况的方法。
• US8088763B2
  申请人：——

  公开号：US8088763B2

  公开（公告）日：2012-01-03
• Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D QSAR Studies of Phenethylamine Derivatives
  作者：Won Suck Sun、Yoon Sun Park、Jakyung Yoo、Ki Duk Park、Sung Han Kim、Jung-Han Kim、Hyun-Ju Park

  DOI：10.1021/jm0205346

  日期：2003.12.1

  A series of 45 phenethylamine derivatives were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (ALR2, EC 1.1.1.21). Their IC50 values ranged from 400 muM to 24 muM. The binding modes of compounds at the active site of ALR2 were examined using flexible docking. The results indicated that phenethylamine derivatives nicely fit into the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of the compounds. The best prediction was obtained by CoMSIA combined with hydrophobic and hydrogen bond donor/acceptor field (q(2) = 0.557, r(2) = 0.934). A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking into account the CoMSIA field and the binding mode derived by FlexX docking. This rationally designed compound exhibits an ALR2 inhibition with an IC50 value of 7.4 muM, which compares favorably to that of a well-known ALR2 inhibitor, tolrestat (IC50 = 16 muM) and represents a potency approximately 240-fold higher than that of an original phenethylamine lead compound, YUA001.