4-(S)-(2-amino-butyryl)-piperazine-1-carboxylic acid butyl ester | 1073556-09-8

• 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: 4-(S)-(2-amino-butyryl)-piperazine-1-carboxylic acid butyl ester
• 英文别名: butyl 4-[(2S)-2-aminobutanoyl]piperazine-1-carboxylate
• CAS: 1073556-09-8
• 化学式: C₁₃H₂₅N₃O₃
• 分子量: 271.36
• InChiKey: KANWUEPFTWJYHT-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氯-2-苯基嘧啶-4-羧酸 、 4-(S)-(2-amino-butyryl)-piperazine-1-carboxylic acid butyl ester 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 2.17h， 生成 4-(S)-{2-[(6-chloro-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid butyl ester
  参考文献：
  名称：

  [EN] 6-(3-AZA-BICYCLO[3.1.0]HEX-3-YL)-2-PHENYL-PYRIMIDINES AS ADP RECEPTOR ANTAGONISTS
  [FR] 6-(3-AZABICYCLO[3.1.0]HEX-3-YL)-2-PHÉNYLPYRIMIDINES

  摘要：

  公开号：

  WO2010116328A3

文献信息

• QUINOLINE-CARBOXAMIDE DERIVATIVES AS P2Y12 ANTAGONISTS
  申请人：Nazaré Marc

  公开号：US20100135999A1

  公开（公告）日：2010-06-03

  The present invention relates to compounds of the formula I, in which R 1 ; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; Z; A; B; E; X; Q; J; V; G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong anti-aggregating effect on platelets and thus an anti-thrombotic effect and are suitable e.g. for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible antagonists of the platelet ADP receptor P2Y12, and can in general be applied in conditions in which an undesired activation of the platelet ADP receptor P2Y12 is present or for the cure or prevention of which an inhibition of the platelet ADP receptor P2Y12 is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及公式I的化合物，其中R1; R2; R3; R4; R5; R6; Z; A; B; E; X; Q; J; V; G和M具有所述声明中指示的含义。公式I的化合物是有价值的药理活性化合物。它们对血小板具有强烈的抗聚集作用，从而具有抗血栓作用，适用于治疗和预防心血管疾病，如血栓栓塞病或再狭窄。它们是血小板ADP受体P2Y12的可逆拮抗剂，通常适用于存在不良激活血小板ADP受体P2Y12的情况，或者治愈或预防需要抑制血小板ADP受体P2Y12的情况。此外，本发明还涉及制备公式I化合物的方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的制药制剂。
• 6-(3-AZA-BICYCLO[3.1.0]HEX-3-YL)-2-PHENYL-PYRIMIDINES
  申请人：Caroff Eva

  公开号：US20120028989A1

  公开（公告）日：2012-02-02

  The present invention relates to 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidine derivatives 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.

  本发明涉及6-(3-aza-bicyclo[3.1.0]hex-3-yl)-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，包括在人类和其他哺乳动物中的血栓形成的使用。
• 4-((<i>R</i>)-2-{[6-((<i>S</i>)-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
  作者：Eva Caroff、Francis Hubler、Emmanuel Meyer、Dorte Renneberg、Carmela Gnerre、Alexander Treiber、Markus Rey、Patrick Hess、Beat Steiner、Kurt Hilpert、Markus A. Riederer

  DOI：10.1021/acs.jmedchem.5b00933

  日期：2015.12.10

  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.
• 6-(3-AZA-BICYCLO[3.1.0]HEX-3-YL)-2-PHENYL-PYRIMIDINES AS ADP RECEPTOR ANTAGONISTS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP2417128B1

  公开（公告）日：2016-03-02
• US8288385B2
  申请人：——

  公开号：US8288385B2

  公开（公告）日：2012-10-16