2S-N-Cbz-高丝氨酸二环己胺盐 | 58578-43-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2S-N-Cbz-高丝氨酸二环己胺盐
• 英文名称: dicyclohexylammonium (2S)-2-(benzyloxycarbonylamino)-4-hydroxybutyrate
• 英文别名: (S)-2-benzyloxycarbonylamino-4-hydroxybutyric acid dicyclohexylamine salt；2S-N-Cbz-Homoserine Cyclohexanamine；N-cyclohexylcyclohexanamine;(2S)-4-hydroxy-2-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 58578-43-1
• 化学式: C₁₂H₁₅NO₅*C₁₂H₂₃N
• 分子量: 434.576
• InChiKey: HWYVLXXGARLCRX-PPHPATTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2S-N-Cbz-高丝氨酸二环己胺盐 在 四溴化碳 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 methyl (2S)-2-(benzyloxycarbonylamino)-4-bromobutanoate
  参考文献：
  名称：

  4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y₁₂ Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel

  摘要：

  Recent post hoc analyses of several clinical trials with P2Y(12) antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y(12) antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.

  DOI：

  10.1021/acs.jmedchem.5b00933
• 作为产物：
  描述：

  氯甲酸苄酯 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 2S-N-Cbz-高丝氨酸二环己胺盐
  参考文献：
  名称：

  二聚金催化剂光介导醇脱氧

  摘要：

  探索了一种用于伯醇还原脱氧的新方案。这种光介导的方法结合了一种新的醇溴化方法，结合了 [Au2(dppm)2]Cl2 [dppm = 1,1-双(二苯基膦)甲烷] 作为光氧化还原催化剂的强大还原能力。所讨论的高效方法的特点是使用 UVA 发光二极管，其显着缩短了反应时间并降低了设置成本。

  DOI：

  10.1002/ejoc.201403351

文献信息

• [EN] PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDE PHOSPHONIQUE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU RÉCEPTEUR P2Y12
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009069100A1

  公开（公告）日：2009-06-04

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  这项发明涉及含有膦酸基团的2-苯基嘧啶衍生物，以及它们作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或状况中的使用，包括人类和其他哺乳动物中的血栓形成。（I）。
• The total synthesis of rhizobitoxine
  作者：D.D. Keith、J.A. Tortora、K. Ineichen、W. Leimgruber

  DOI：10.1016/0040-4020(75)80282-1

  日期：1975.1

  The assignment of structure 1 to rhizobitoxine, an amino acid produced by Rhizobium japonicum, has been confirmed by total synthesis.

  通过全合成已经证实了结构1分配给根瘤菌毒素（一种由日本根瘤菌产生的氨基酸）。
• Concise Synthesis of Enantiomerically Pure (1'S,2'R)- and (1'R,2'S)-2S-Amino-3-(2'-aminomethyl-cyclopropyl)propionic Acid: Two E-Diastereoisomers of 4,5-Methano-L-lysine
  作者：Timothy M. Altamore、Oanh T. K. Nguyen、Quentin I. Churches、Kate Cavanagh、Xuan T. T. Nguyen、Sandhya A. M. Duggan、Guy Y. Krippner、Peter J. Duggan

  DOI：10.1071/ch13309

  日期：——

  A concise synthesis of both E-isomers of 2S-amino-3-(2′-aminomethyl-cyclopropyl)propionic acid, new methano-l-lysines, is described. The synthetic route includes nine steps from l-methionine, with a key step involving the cyclopropanation of an intermediate E-allylic alcohol. The resultant hydroxymethylcyclopropanes were readily separated and converted into the title α-amino acids. The stereochemistry

  描述了2 S-氨基-3-（2'-氨基甲基-环丙基）丙酸的两种E-异构体的简明合成，即新的甲基-1-赖氨酸。合成途径包括从1-甲硫氨酸开始的九个步骤，关键步骤包括中间体E-烯丙基醇的环丙烷化。容易地分离所得的羟甲基环丙烷并转化为标题α-氨基酸。在N，N，N'，N'-四甲基-d的存在下进行环丙烷化，推导出环丙烷环周围的立体化学。-酒石酸二酰胺丁基硼酸酯，一种手性控制剂，已知它有利于由烯丙基醇生产S-羟甲基环丙烷。
• PHOSPHONIC ACID DERIVATES AD THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
  申请人：Caroff Eva

  公开号：US20100261678A1

  公开（公告）日：2010-10-14

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y 12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  本发明涉及含有膦酸基团的2-苯基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的病症，包括人类和其他哺乳动物的血栓形成中的应用。(I)。
• PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2225253A1

  公开（公告）日：2010-09-08