{[(S)-3-[((S)-1-Carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-methyl-amino}-acetic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: {[(S)-3-[((S)-1-Carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-methyl-amino}-acetic acid
• 英文别名: 2-[[(2S)-4-[[(3S)-1-carbamimidoylpiperidin-3-yl]methylamino]-2-(naphthalen-2-ylsulfonylamino)-4-oxobutanoyl]-methylamino]acetic acid
• 化学式: C₂₄H₃₂N₆O₆S
• 分子量: 532.621
• InChiKey: CWGSMPMUFUDPTQ-JXFKEZNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  194
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  {[(S)-3-[((S)-1-Carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-methyl-amino}-acetic acid ethyl ester; hydrochloride 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 {[(S)-3-[((S)-1-Carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-methyl-amino}-acetic 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

• N-amidopiperidinyl (3/4)-oder N-amidino-1,4-oxazinyl(2)-substituierte Sulfonamide, Verfahren zur Herstellung und Verwendung als Thrombin-Inhibitoren
  申请人：F.HOFFMANN-LA ROCHE & CO. AKTIENGESELLSCHAFT

  公开号：EP0559046A1

  公开（公告）日：1993-09-08

  Die neuen Sulfonamidocarboxamide der Formel worin Xeine Gruppe der Formel X¹ oder X²: TCH₂ oder O, und A, M, Q, und Y die in der Beschreibung angegebene Bedeutung haben, sowie Hydrate oder Solvate davon hemmen die durch Thrombin induzierte Plättchenaggregation und Gerinnung von Fibrinogen im Plasma. Sie werden hergestellt durch Amidinierung einer für die Gruppierung X stehenden cyclischen Aminogruppe oder durch C(O)N(Q) Amidbildung.

  新的磺酰胺类甲酰胺的化学式为 式中 X 是式 X¹ 或 X² 的基团： TCH₂ 或 O、 和 A、M、Q 和 Y 具有说明中给出的含义，其水合物或溶液可抑制凝血酶诱导的血小板聚集和血浆中纤维蛋白原的凝固。它们是通过代表基团 X 的环状氨基酰胺化或通过 C(O)N(Q) 酰胺形成制备的。
• US5405854A
  申请人：——

  公开号：US5405854A

  公开（公告）日：1995-04-11
• US5578594A
  申请人：——

  公开号：US5578594A

  公开（公告）日：1996-11-26
• Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors
  作者：Kurt Hilpert、Jean Ackermann、David W. Banner、Alain Gast、Klaus Gubernator、Paul Hadvary、Ludvik Labler、Klaus Mueller、Gerard Schmid、Thomas B. Tschopp、Han van de Waterbeemd

  DOI：10.1021/jm00049a008

  日期：1994.11.1

  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.