ethyl (2R)-2-<4-<<(3S)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl>oxy>phenyl>-3-(7-cyano-2-naphthyl)propanoate | 150610-56-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: ethyl (2R)-2-<4-<<(3S)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl>oxy>phenyl>-3-(7-cyano-2-naphthyl)propanoate
• 英文别名: tert-butyl (3S)-3-[4-[(2R)-3-(7-cyanonaphthalen-2-yl)-1-ethoxy-1-oxopropan-2-yl]phenoxy]pyrrolidine-1-carboxylate
• CAS: 150610-56-3
• 化学式: C₃₁H₃₄N₂O₅
• 分子量: 514.621
• InChiKey: NMJRXFTUIGIPII-WUFINQPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  88.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (2R)-2-<4-<<(3S)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl>oxy>phenyl>-3-(7-cyano-2-naphthyl)propanoate 在 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成
  参考文献：
  名称：

  Dibasic (Amidinoaryl)propanoic Acid Derivatives as Novel Blood Coagulation Factor Xa Inhibitors

  摘要：

  Since activated factor X (FXa) is a coagulant enzyme that generates thrombin and participates in both intrinsic and extrinsic coagulation pathways, inhibition of FXa may be more effective than inactivation of thrombin for interrupting blood coagulation. To assess the possible effectiveness of FXa inhibition as an anticoagulant, we designed and synthesized 3-(amidinoaryl)-2-[4-[(3S)-3-pyrrolidinyloxyl phenyl]propanoic acid derivatives as low molecular weight, nonpeptidic, orally active FXa inhibitors. These derivatives exhibited potent and highly selective anti-FXa activity in vitro and anticoagulant activity on oral administration. The most promising compound, (2S)-2-[4-[(3S)-1- acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (4, DX-9065a), inhibited 50% of FXa activity (IC50) at 0.07 mu M, doubled plasma recalcification time (PRCT) at 0.5 mu M, and significantly prolonged activated partial thromboplastin time (APTT) at a dose of 100 mg/kg on oral administration. In contrast with FXa inhibition, 4 showed no activity against thrombin (IC50 > 2000 mu M).

  DOI：

  10.1021/jm00034a018
• 作为产物：
  描述：

  2-(4-羟苯基)-2-氧代乙酸乙酯 在 palladium(II) oxide 、 barium sulfate 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 7.75h， 生成 ethyl (2R)-2-<4-<<(3S)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl>oxy>phenyl>-3-(7-cyano-2-naphthyl)propanoate
  参考文献：
  名称：

  Dibasic (Amidinoaryl)propanoic Acid Derivatives as Novel Blood Coagulation Factor Xa Inhibitors

  摘要：

  Since activated factor X (FXa) is a coagulant enzyme that generates thrombin and participates in both intrinsic and extrinsic coagulation pathways, inhibition of FXa may be more effective than inactivation of thrombin for interrupting blood coagulation. To assess the possible effectiveness of FXa inhibition as an anticoagulant, we designed and synthesized 3-(amidinoaryl)-2-[4-[(3S)-3-pyrrolidinyloxyl phenyl]propanoic acid derivatives as low molecular weight, nonpeptidic, orally active FXa inhibitors. These derivatives exhibited potent and highly selective anti-FXa activity in vitro and anticoagulant activity on oral administration. The most promising compound, (2S)-2-[4-[(3S)-1- acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (4, DX-9065a), inhibited 50% of FXa activity (IC50) at 0.07 mu M, doubled plasma recalcification time (PRCT) at 0.5 mu M, and significantly prolonged activated partial thromboplastin time (APTT) at a dose of 100 mg/kg on oral administration. In contrast with FXa inhibition, 4 showed no activity against thrombin (IC50 > 2000 mu M).

  DOI：

  10.1021/jm00034a018

文献信息

• Dibasic (Amidinoaryl)propanoic Acid Derivatives as Novel Blood Coagulation Factor Xa Inhibitors
  作者：Takayasu Nagahara、Yukio Yokoyama、Kazue Inamura、Shin-ichi Katakura、Satoshi Komoriya、Hitoshi Yamaguchi、Tsuyoshi Hara、Masahiro Iwamoto

  DOI：10.1021/jm00034a018

  日期：1994.4

  Since activated factor X (FXa) is a coagulant enzyme that generates thrombin and participates in both intrinsic and extrinsic coagulation pathways, inhibition of FXa may be more effective than inactivation of thrombin for interrupting blood coagulation. To assess the possible effectiveness of FXa inhibition as an anticoagulant, we designed and synthesized 3-(amidinoaryl)-2-[4-[(3S)-3-pyrrolidinyloxyl phenyl]propanoic acid derivatives as low molecular weight, nonpeptidic, orally active FXa inhibitors. These derivatives exhibited potent and highly selective anti-FXa activity in vitro and anticoagulant activity on oral administration. The most promising compound, (2S)-2-[4-[(3S)-1- acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (4, DX-9065a), inhibited 50% of FXa activity (IC50) at 0.07 mu M, doubled plasma recalcification time (PRCT) at 0.5 mu M, and significantly prolonged activated partial thromboplastin time (APTT) at a dose of 100 mg/kg on oral administration. In contrast with FXa inhibition, 4 showed no activity against thrombin (IC50 > 2000 mu M).