(R)-3-(4-aminophenyl)-2-<(naphth-2-ylsulfonyl)amino>propionic acid | 140645-73-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-3-(4-aminophenyl)-2-<(naphth-2-ylsulfonyl)amino>propionic acid
• 英文别名: 3-(p-aminophenyl)-N-(2-naphthylsulfonyl)-D-alanine；(2R)-3-(4-aminophenyl)-2-(naphthalen-2-ylsulfonylamino)propanoic acid
• CAS: 140645-73-4
• 化学式: C₁₉H₁₈N₂O₄S
• 分子量: 370.429
• InChiKey: UWTHONUVTLWJQP-GOSISDBHSA-N

物化性质

• 沸点：
  647.2±65.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-aminophenyl)-2-<(naphth-2-ylsulfonyl)amino>propionic acid 在 N-乙基吗啉 、 吡啶 、 dowex 、 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 生成 (R)-3-(4-Acetylamino-phenyl)-N-(1-carbamimidoyl-piperidin-3-ylmethyl)-2-(naphthalene-2-sulfonylamino)-propionamide; hydrochloride
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008
• 作为产物：
  描述：

  2-萘磺酰氯 在 镍 sodium hydroxide 、 氢气 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 54.0h， 生成 (R)-3-(4-aminophenyl)-2-<(naphth-2-ylsulfonyl)amino>propionic acid
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008

文献信息

• Guanidine derivatives compositions and use
  申请人：Hofmann-La Roche Inc.

  公开号：US05260307A1

  公开（公告）日：1993-11-09

  Compounds of the formula ##STR1## wherein L, M, R, T and X are set forth in the description, as well as hydrates or solvates thereof, which inhibit thrombin-induced platelet aggregation and clotting of fibrinogen in plasma, are described. The compounds of formula I are prepared by amidination or, depending on whether L is NH or O, by amide formation or esterification.

  式中L、M、R、T和X在描述中阐述的化合物I，以及其水合物或溶剂化物，可以抑制血浆中凝血酶诱导的血小板聚集和纤维蛋白原的凝结。化合物I可以通过酰胺化或酯化反应来制备，具体取决于L是NH还是O。
• Guanidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05595999A1

  公开（公告）日：1997-01-21

  Compounds of the formula ##STR1## wherein L, M, R, T and X are set forth in the description, as well as hydrates or solvates thereof, which inhibit thrombin-induced platelet aggregation and clotting of fibrinogen in plasma, are described. The compounds of formula I are prepared by amidination or, depending on whether L is NH or O, by amide formation or esterification.

  该文描述了公式##STR1##中L，M，R，T和X所示的化合物及其水合物或溶剂化物，这些化合物能够抑制血栓素诱导的血小板聚集和血浆中纤维蛋白原的凝固。公式I的化合物通过酰胺化或酰胺形成或酯化制备，具体取决于L是NH还是O。
• Guanidine
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0468231B1

  公开（公告）日：1994-09-21
• US5260307A
  申请人：——

  公开号：US5260307A

  公开（公告）日：1993-11-09
• US5393760A
  申请人：——

  公开号：US5393760A

  公开（公告）日：1995-02-28