t-butyl (S)-3-t-butoxycarbonylamino-N-ethoxycarbonylmethyl-N-methylsuccinamate | 155541-37-0

• 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: t-butyl (S)-3-t-butoxycarbonylamino-N-ethoxycarbonylmethyl-N-methylsuccinamate
• 英文别名: Boc-Asp(OtBu)-Sar-OEt；tert-butyl (3S)-4-[(2-ethoxy-2-oxoethyl)-methylamino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 155541-37-0
• 化学式: C₁₈H₃₂N₂O₇
• 分子量: 388.461
• InChiKey: YGZPUWOFGSQLHX-LBPRGKRZSA-N

物化性质

• 沸点：
  502.1±50.0 °C(predicted)
• 密度：
  1.110±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  t-butyl (S)-3-t-butoxycarbonylamino-N-ethoxycarbonylmethyl-N-methylsuccinamate 在 盐酸 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 乙腈 为溶剂， 反应 13.0h， 生成 (S)-N-Ethoxycarbonylmethyl-N-methyl-3-(naphthalene-2-sulfonylamino)-succinamic 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
• 作为产物：
  描述：

  2-(甲基氨基)乙酸乙酯 、 叔丁氧羰基-L-天冬氨酸-4-叔丁酯 在 N-乙基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 t-butyl (S)-3-t-butoxycarbonylamino-N-ethoxycarbonylmethyl-N-methylsuccinamate
  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

• Sulfonamidocarboxamides
  申请人：Hoffmann-La Roche Inc.

  公开号：US05405854A1

  公开（公告）日：1995-04-11

  Sulfonamidocarboxamides of the formula ##STR1## wherein A, M, Q, X and Y have the significance given in the description, as well as hydrates, solvates and salts thereof, which inhibit thrombin-induced blood platelet aggregation and clotting of fibrinogen in plasma, as described. The compounds of formula I can be prepared by amidination of a cyclic amino group standing for grouping X or by C(O)N(Q) amide formation.

  翻译结果如下： 公式##STR1##中的磺酰氨基甲酰胺，其中A、M、Q、X和Y的含义如描述中所述，以及它们的 hydrates（水合物）、solvates（溶剂合物）和盐，这些化合物能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，如所述。公式I的化合物可以通过对代表X基团的环状氨基进行酰胺化反应，或者通过C(O)N(Q)酰胺形成来制备。
• 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。