5-Methyl-2-(2-nitro-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester | 1027239-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-Methyl-2-(2-nitro-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-methyl-2-(2-nitrophenyl)pyrazole-3-carboxylate
• CAS: 1027239-00-4
• 化学式: C₁₃H₁₃N₃O₄
• 分子量: 275.264
• InChiKey: JNVCBHLOPLPEIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-Methyl-2-(2-nitro-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester 在 palladium on activated charcoal 氢气 、 三甲基铝 、 三氟乙酸 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 20.0~40.0 ℃ 、101.33 kPa 条件下， 反应 22.25h， 生成 1-(2-aminophenyl)-3-methyl-N-[4-(2-sulfamoylphenyl)phenyl]-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants

  摘要：

  As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K-i of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  DOI：

  10.1021/jm020578e
• 作为产物：
  描述：

  2-硝基苯肼 、 2-(甲氧基亚胺)-4-氧代-戊酸乙酯 以 乙醇 为溶剂， 反应 5.0h， 生成 5-Methyl-2-(2-nitro-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants

  摘要：

  As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K-i of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  DOI：

  10.1021/jm020578e