Methyl 3-(3-cyanophenyl)-5-[4-[(2,4-dimethoxyphenyl)methylcarbamoyl]phenyl]pentanoate | 200481-69-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: Methyl 3-(3-cyanophenyl)-5-[4-[(2,4-dimethoxyphenyl)methylcarbamoyl]phenyl]pentanoate
• CAS: 200481-69-2
• 化学式: C₂₉H₃₀N₂O₅
• 分子量: 486.568
• InChiKey: VYILPCZTRSXERJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  97.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 3-(3-cyanophenyl)-5-[4-[(2,4-dimethoxyphenyl)methylcarbamoyl]phenyl]pentanoate 在 ammonium carbonate 、 盐酸 、 cerric ammonium sulphate 作用下， 以 水 、 乙腈 为溶剂， 反应 56.0h， 生成 3-(3-Carbamimidoyl-phenyl)-5-(4-carbamoyl-phenyl)-pentanoic acid methyl ester
  参考文献：
  名称：

  Rational Design and Synthesis of Novel, Potent Bis-phenylamidine Carboxylate Factor Xa Inhibitors

  摘要：

  The molecular modeling studies, rational design, and synthesis of a novel series of bis-phenylamidine carboxylate compounds which are inhibitors of factor Xa in the blood coagulation cascade are described. Inhibition of blood coagulation has been proposed to have several potential therapeutic utilities (Kaiser and Hauptmann, Cardiovasc. Drug Rev. 1994, 12, 225-236). Factor Xa (fXa) holds a central position in the coagulation cascade (Coleman et al. in Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 1994, pp 3-18). Its major role is the generation of thrombin by the proteolytic cleavage of prothrombin. Inhibition of fXa would serve to reduce the formation of platelet clots. The fXa dimer crystal structure (Tulinsky et al., J. Mol. Biol. 1993, 232, 947-966) was used in our molecular modeling studies to design a novel series of fXa inhibitors. We initially docked and minimized isolated small molecule fragments in the S1 and S4 aryl-binding subsites. Subsequently, these fragments were connected with a tether, so as not to disturb the orientation of the fragments in their respective pockets. These modeling studies led to the initial compound (1) which was found to have significant inhibitory potency for fXa (K-i = 34 nM). The synthesis of the core structure, structure-activity relationships (SAR), and proposed binding orientation based on molecular modeling for this novel bis-phenylamidine series of fXa inhibitors are described.

  DOI：

  10.1021/jm970485a
• 作为产物：
  描述：

  2,4-二甲氧基苄胺盐酸盐 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 sodium methylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 25.0~100.0 ℃ 、310.27 kPa 条件下， 反应 24.0h， 生成 Methyl 3-(3-cyanophenyl)-5-[4-[(2,4-dimethoxyphenyl)methylcarbamoyl]phenyl]pentanoate
  参考文献：
  名称：

  Rational Design and Synthesis of Novel, Potent Bis-phenylamidine Carboxylate Factor Xa Inhibitors

  摘要：

  The molecular modeling studies, rational design, and synthesis of a novel series of bis-phenylamidine carboxylate compounds which are inhibitors of factor Xa in the blood coagulation cascade are described. Inhibition of blood coagulation has been proposed to have several potential therapeutic utilities (Kaiser and Hauptmann, Cardiovasc. Drug Rev. 1994, 12, 225-236). Factor Xa (fXa) holds a central position in the coagulation cascade (Coleman et al. in Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 1994, pp 3-18). Its major role is the generation of thrombin by the proteolytic cleavage of prothrombin. Inhibition of fXa would serve to reduce the formation of platelet clots. The fXa dimer crystal structure (Tulinsky et al., J. Mol. Biol. 1993, 232, 947-966) was used in our molecular modeling studies to design a novel series of fXa inhibitors. We initially docked and minimized isolated small molecule fragments in the S1 and S4 aryl-binding subsites. Subsequently, these fragments were connected with a tether, so as not to disturb the orientation of the fragments in their respective pockets. These modeling studies led to the initial compound (1) which was found to have significant inhibitory potency for fXa (K-i = 34 nM). The synthesis of the core structure, structure-activity relationships (SAR), and proposed binding orientation based on molecular modeling for this novel bis-phenylamidine series of fXa inhibitors are described.

  DOI：

  10.1021/jm970485a

文献信息

• Rational Design and Synthesis of Novel, Potent Bis-phenylamidine Carboxylate Factor Xa Inhibitors
  作者：Thomas P. Maduskuie,、Kevin J. McNamara、Yu Ru、Robert M. Knabb、Pieter F. W. Stouten

  DOI：10.1021/jm970485a

  日期：1998.1.1

  The molecular modeling studies, rational design, and synthesis of a novel series of bis-phenylamidine carboxylate compounds which are inhibitors of factor Xa in the blood coagulation cascade are described. Inhibition of blood coagulation has been proposed to have several potential therapeutic utilities (Kaiser and Hauptmann, Cardiovasc. Drug Rev. 1994, 12, 225-236). Factor Xa (fXa) holds a central position in the coagulation cascade (Coleman et al. in Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 1994, pp 3-18). Its major role is the generation of thrombin by the proteolytic cleavage of prothrombin. Inhibition of fXa would serve to reduce the formation of platelet clots. The fXa dimer crystal structure (Tulinsky et al., J. Mol. Biol. 1993, 232, 947-966) was used in our molecular modeling studies to design a novel series of fXa inhibitors. We initially docked and minimized isolated small molecule fragments in the S1 and S4 aryl-binding subsites. Subsequently, these fragments were connected with a tether, so as not to disturb the orientation of the fragments in their respective pockets. These modeling studies led to the initial compound (1) which was found to have significant inhibitory potency for fXa (K-i = 34 nM). The synthesis of the core structure, structure-activity relationships (SAR), and proposed binding orientation based on molecular modeling for this novel bis-phenylamidine series of fXa inhibitors are described.