7-<(ethoxycarbonyl)<4-(tetrahydro-pyran-4-yloxy)phenyl>methoxy>-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester | 218922-89-5

• 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: 7-<(ethoxycarbonyl)<4-(tetrahydro-pyran-4-yloxy)phenyl>methoxy>-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 7-[2-ethoxy-1-[4-(oxan-4-yloxy)phenyl]-2-oxoethoxy]-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 218922-89-5
• 化学式: C₂₉H₃₇NO₇
• 分子量: 511.615
• InChiKey: ZVCLYBMBIDFXNF-UHFFFAOYSA-N

物化性质

• 沸点：
  635.912±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.188±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  83.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-<(ethoxycarbonyl)<4-(tetrahydro-pyran-4-yloxy)phenyl>methoxy>-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 5.0h， 以99%的产率得到(1,2,3,4-tetrahydro-isoquinolin-7-yloxy)<4-(tetrahydropyran-4-yloxy)phenyl>acetic acid ethyl ester hydrochloride
  参考文献：
  名称：

  Tetrahydro-isoquinoline-Based Factor Xa Inhibitors

  摘要：

  Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7-yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K-i = 21-55 nM but do not inhibit thrombin (K-i = 5->100 mu M) and only weakly inhibit trypsin (K-i = 0.08-5 mu M). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.

  DOI：

  10.1021/jm9800402
• 作为产物：
  描述：

  1,2,3,4-四氢异喹啉-7-醇 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 100.0h， 生成 7-<(ethoxycarbonyl)<4-(tetrahydro-pyran-4-yloxy)phenyl>methoxy>-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Tetrahydro-isoquinoline-Based Factor Xa Inhibitors

  摘要：

  Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7-yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K-i = 21-55 nM but do not inhibit thrombin (K-i = 5->100 mu M) and only weakly inhibit trypsin (K-i = 0.08-5 mu M). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.

  DOI：

  10.1021/jm9800402

文献信息

• Tetrahydro-isoquinoline-Based Factor Xa Inhibitors
  作者：Ralf Kucznierz、Frank Grams、Herbert Leinert、Klaus Marzenell、Richard A. Engh、Wolfgang von der Saal

  DOI：10.1021/jm9800402

  日期：1998.12.1

  Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7-yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K-i = 21-55 nM but do not inhibit thrombin (K-i = 5->100 mu M) and only weakly inhibit trypsin (K-i = 0.08-5 mu M). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.