3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({[(2-hydroxyethyl)carbamoyl](methyl)amino}methyl)thiophene-2-carboxamide | 229335-55-1

• 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: 3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({[(2-hydroxyethyl)carbamoyl](methyl)amino}methyl)thiophene-2-carboxamide
• 英文别名: 3-chloro-N-[4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl]-4-[[2-hydroxyethylcarbamoyl(methyl)amino]methyl]thiophene-2-carboxamide
• CAS: 229335-55-1
• 化学式: C₂₃H₂₂Cl₃N₅O₅S
• 分子量: 586.883
• InChiKey: RTZIXXQWZLORDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({[(2-hydroxyethyl)carbamoyl](methyl)amino}methyl)thiophene-2-carboxamide 在 chloroacetaldehyde diethylacetal 作用下， 以 乙醇 为溶剂， 反应 96.0h， 生成 N-(5-chloropyridin-2-yl)-2-[((4-((N'-methyl-N'-(oxazol-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide
  参考文献：
  名称：

  Thiophene-Anthranilamides as Highly Potent and Orally Available Factor Xa Inhibitors

  摘要：

  There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.

  DOI：

  10.1021/jm070125f
• 作为产物：
  描述：

  3-甲氧基-2-硝基苯甲酰氯 在 4-二甲氨基吡啶 吡啶 、 sodium disulfite 、 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 28.5h， 生成 3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({[(2-hydroxyethyl)carbamoyl](methyl)amino}methyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Thiophene-Anthranilamides as Highly Potent and Orally Available Factor Xa Inhibitors

  摘要：

  There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.

  DOI：

  10.1021/jm070125f