3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile
• 英文别名: 3-[(E)-3-(4-cyanophenyl)prop-2-enoyl]benzonitrile
• 化学式: C₁₇H₁₀N₂O
• 分子量: 258.279
• InChiKey: HOSNPDVNCBHSLB-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile 在 palladium on activated charcoal lithium hydroxide 、 草酰氯 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 25.0~100.0 ℃ 、310.27 kPa 条件下， 反应 31.0h， 生成 4-(cyano)-beta-(3-cyanophenyl)-N-methylbenzenepentanamide
  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：

  3-乙酰苯腈 、 4-氰基苯甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以97%的产率得到3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile
  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

• .alpha.-branched anilines, toluenes, and analogs thereof as factor Xa
  申请人：DuPont Pharmaceuticals Company

  公开号：US05942544A1

  公开（公告）日：1999-08-24

  The present application describes m-amidino phenyl analogs of formula I: ##STR1## wherein D can be amidino and E can be phenyl, which are useful as inhibitors of factor Xa.

  本申请描述了式I的m-氨基甘氨酰苯类似物：##STR1## 其中D可以是氨基甘氨酰，E可以是苯基，它们可用作因子Xa的抑制剂。
• M-AMIDINO PHENYL ANALOGS AS FACTOR Xa INHIBITORS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP0892780B1

  公开（公告）日：2002-11-20
• [EN] M-AMIDINO PHENYL ANALOGS AS FACTOR Xa INHIBITORS<br/>[FR] ANALOGUES DU M-AMIDINO PHENYLE COMME INHIBITEURS DU FACTEUR Xa
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1997030971A1

  公开（公告）日：1997-08-28

  (EN) The present application describes m-amidino phenyl analogs of formula (I), wherein D can be amidino and E can be phenyl, which are useful as inhibitors of factor Xa.(FR) La présente invention concerne des analogues du m-amidino phényle présentant la formule (I). Dans cette dernière, B peut être de l'amidino et E du phényle. Ces analogues constituent des inhibiteurs utiles du facteur Xa.
• 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.