N-(2-hydroxyethyl)-1-(4-iodophenyl)cyclopropane-1-carboxamide | 630384-42-8

• 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: N-(2-hydroxyethyl)-1-(4-iodophenyl)cyclopropane-1-carboxamide
• CAS: 630384-42-8
• 化学式: C₁₂H₁₄INO₂
• 分子量: 331.153
• InChiKey: IWTRNGVLCPKOOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyethyl)-1-(4-iodophenyl)cyclopropane-1-carboxamide 在 copper(l) iodide 、 1,10-菲罗啉 、 伯吉斯试剂 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6-{4-[1-(4,5-dihydro-oxazol-2-yl)cyclopropyl]phenyl}-1-(4-methoxyphenyl)-3-trifluoromethyl-1,4,5,6-tetrahydropyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties

  摘要：

  We previously disclosed a series of highly potent FXa inhibitors bearing alpha-substituted ((CH2NRR2)-R-1) phenylcyclopropyl P4 moieties in the pyrazolodihydropyridone core system. Herein, we describe our continuous SAR efforts in this series. Effects of the C-3 substitution of the pyrazolodihydropyridone core and the alpha-substitution (R group) of the cyclopropyl ring on FXa binding affinity (FXa K-i), human plasma anticoagulant activity (PT EC2x) and permeability are discussed. A set of compounds obtained from optimization of the R group and the C-3 substituent were orally bioavailable in dogs. Furthermore, representative compounds were highly efficacious in the rabbit arterio-venous shunt thrombosis model (EC(50)s = 29-81 nM). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.049
• 作为产物：
  描述：

  1-(4-碘苯基)环丙烷羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 反应 3.5h， 生成 N-(2-hydroxyethyl)-1-(4-iodophenyl)cyclopropane-1-carboxamide
  参考文献：
  名称：

  Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties

  摘要：

  We previously disclosed a series of highly potent FXa inhibitors bearing alpha-substituted ((CH2NRR2)-R-1) phenylcyclopropyl P4 moieties in the pyrazolodihydropyridone core system. Herein, we describe our continuous SAR efforts in this series. Effects of the C-3 substitution of the pyrazolodihydropyridone core and the alpha-substitution (R group) of the cyclopropyl ring on FXa binding affinity (FXa K-i), human plasma anticoagulant activity (PT EC2x) and permeability are discussed. A set of compounds obtained from optimization of the R group and the C-3 substituent were orally bioavailable in dogs. Furthermore, representative compounds were highly efficacious in the rabbit arterio-venous shunt thrombosis model (EC(50)s = 29-81 nM). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.049
• 作为试剂：
  描述：

  1-(4-碘苯基)环丙烷羧酸 、 草酰氯 、 C.I.酸性橙108 、 methoxycarbonylsulfamoyl-triethylammmonium hydroxide 在 氮 、 二氯甲烷 、 水 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 N-(2-hydroxyethyl)-1-(4-iodophenyl)cyclopropane-1-carboxamide 、 silica 作用下， 以 二氯甲烷 、 四氢呋喃 、 乙酸乙酯 、 EtOAc Hexanes 、 acetonitrile-water 为溶剂， 反应 4.57h， 生成 2-[1-(4-iodophenyl)cyclopropyl]-4,5-dihydrooxazole
  参考文献：
  名称：

  1,1-Disubstituted cycloalkyl derivatives as factor Xa inhibitors

  摘要：

  本申请描述了1,1-二取代环烷基化合物及其衍生物，或其药学上可接受的盐形式，这些化合物可用作因子Xa的抑制剂。

  公开号：

  US20040254158A1