2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯 | 221136-66-9

• 物质功能分类: 医药中间体 - 原料药中间体
• 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
• 中文名称: 2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯
• 中文别名: 3-溴-6-甲基-2-氧代-1(2h)-吡嗪乙酸乙酯
• 英文名称: 3-bromo-1-(ethoxycarbonylmethyl)-6-methylpyrazinone
• 英文别名: 3-bromo-6-methyl-2-oxo-1(2H)-pyrazineacetic acid ethyl ester；ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1(2H)-yl)acetate；ethyl 3-bromo-6-methylpyrazin-(1H)-2-one-1-acetate；(3-bromo-6-methyl-2-oxo-2H-pyrazin-1-yl)-acetic acid ethyl ester；3-bromo-6-methyl-1-(ethoxycarbonylmethyl)pyrazinone；ethyl 2-(3-bromo-6-methyl-2-oxopyrazin-1-yl)acetate
• CAS: 221136-66-9
• 化学式: C₉H₁₁BrN₂O₃
• 分子量: 275.102
• InChiKey: NHAOOSRGGOXZGW-UHFFFAOYSA-N

物化性质

• 沸点：
  338.3±44.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  存储条件为2-8°C，并需保存在惰性气体中。

反应信息

• 作为反应物：
  描述：

  2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯 在 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 15.0h， 生成 N-((4R,5S)-2-Amino-4-methyl-1,4,5,6-tetrahydro-pyrimidin-5-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide
  参考文献：
  名称：

  Non-covalent thrombin inhibitors featuring p 3 -heterocycles with P 1 -monocyclic arginine surrogates

  摘要：

  Investigations on P-2-P-3-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P-1-arginine derivatives. The design. synthesis. and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P-1-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydrox amidines, (2) 2-aminopyrazines. and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00129-4
• 作为产物：
  描述：

  2-[(2-乙氧基-2-氧代乙基)氨基]-2-氧代乙酸乙酯 在 ruthenium trichloride 、 sodium bromate 、 disodium hydrogenphosphate 、 三氟乙酸 、 三氟乙酸酐 、 三溴氧磷 作用下， 以 醋酸异丙酯 、 水 、 溶剂黄146 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 43.5h， 生成 2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯
  参考文献：
  名称：

  Kilogram Scale Synthesis of the Pyrazinone Acetic Acid Core of an Orally Efficacious Thrombin Inhibitor

  摘要：

  A multi-kilogram scale synthesis of the orally efficacious thrombin inhibitor 1 has been achieved via construction of the pyrazinone core from an unsymmetric oxalic diamide. Key features include judicious choice of reagents to minimize side products, a key ruthenium catalyzed oxidation, and development of reaction conditions amenable to large-scale synthesis.

  DOI：

  10.1080/00397910008086927
• 作为试剂：
  描述：

  2,2-二氟-2-苯基乙胺 、 2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯 在 2-(3-溴-6-甲基-2-吡嗪酮-1(2H)-基)乙酸乙酯 作用下， 生成 3-(2,2-Difluoro-2-phenylethylamino)-1-(ethoxycarbonylmethyl)-6-methylpyrazinone
  参考文献：
  名称：

  J. Med. Chem. 2010, 53, 1843-1856

  摘要：

  DOI：

文献信息

• Thrombin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06610692B1

  公开（公告）日：2003-08-26

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is NY or O; c is CY2 or N; d is CY3 or N; e is CY4 or N; f is CY5 or N; g is CY6 or N; Y4, Y5, and Y6 are independently hydrogen, C1-4 alkyl, or halogen; Y1 and Y2 are independently hydrogen, C1-4 alkyl, C3-7 cycloalkyl, halogen, NH2, OH or C1-4 alkoxy, and Y3 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, halogen, —CN, NH2, OH or C1-4 alkoxy; A is and W, W1, R1, R3, R4, R5, X and Z are defined in the specification.

  发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构：或其药学上可接受的盐，其中b为NY或O；c为CY2或N；d为CY3或N；e为CY4或N；f为CY5或N；g为CY6或N；Y4、Y5和Y6独立地为氢、C1-4烷基或卤素；Y1和Y2独立地为氢、C1-4烷基、C3-7环烷基、卤素、NH2、OH或C1-4烷氧基，Y3为氢、C1-4烷基、C3-7环烷基、卤素、—CN、NH2、OH或C1-4烷氧基；A为，并且W、W1、R1、R3、R4、R5、X和Z在规范中有定义。
• MASP-2 INHIBITORS AND METHODS OF USE
  申请人：Omeros Corporation

  公开号：US20190367452A1

  公开（公告）日：2019-12-05

  The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.

  本公开提供了具有MASP-2抑制活性的化合物，这些化合物的组合物以及制造和使用这些化合物的方法。
• Aminoalkyl-pyrazinones and -pyridones as thrombin inhibitors
  申请人：Graffinity Pharmaceuticals Aktiengesellschaft

  公开号：EP1526131A1

  公开（公告）日：2005-04-27

  The invention relates to compounds of formula (I) wherein A, B, X, R1, R2, G, R3, D and E have the meaning as cited in the description and the claims. Said compounds are useful as coagulants. The invention also relates to the production and use thereof as medicament.

  这项发明涉及式(I)的化合物 其中A、B、X、R1、R2、G、R3、D和E的含义如描述和权利要求中所述。所述化合物可用作凝血剂。该发明还涉及其作为药物的生产和使用。
• Discovery and Clinical Evaluation of 1-{<i>N</i>-[2-(Amidinoaminooxy)ethyl]amino}carbonylmethyl-6-methyl-3-[2,2-difluoro-2-phenylethylamino]pyrazinone (RWJ-671818), a Thrombin Inhibitor with an Oxyguanidine P1 Motif
  作者：Tianbao Lu、Thomas Markotan、Shelley K. Ballentine、Edward C. Giardino、John Spurlino、Kathryn Brown、Bruce E. Maryanoff、Bruce E. Tomczuk、Bruce P. Damiano、Umesh Shukla、David End、Patricia Andrade-Gordon、Roger F. Bone、Mark R. Player

  DOI：10.1021/jm901802n

  日期：2010.2.25

  prolonged occlusion time 2- and 3-fold at 0.1 and 1.0 mg/kg, iv, respectively, and more than doubled activated clotting time and activated partial thromboplastin time at the higher dose. This compound had excellent oral bioavailability of 100% in dogs with an estimated half-life of approximately 3 h. On the basis of its noteworthy preclinical data, 8 was advanced into human clinical trials and successfully

  我们已经将RWJ-671818（8）鉴定为一种新型的低分子量人α凝血酶口服活性抑制剂（K i = 1.3 nM），对静脉和动脉血栓形成的急性和慢性治疗具有潜在的作用。在用于评估抗血栓形成功效的大鼠深静脉血栓形成模型中，口服30 mg / kg和50 mg / kg的8分别减少了87％和94％的血栓重量。在麻醉的大鼠抗血栓形成模型中，颈动脉的电刺激产生了血栓，8静脉注射分别延长了0.1和1.0 mg / kg的2倍和3倍的阻塞时间，在较高剂量下，活化凝血时间和活化部分凝血活酶时间延长了一倍以上。该化合物在狗中具有100％的优异口服生物利用度，估计半衰期约为3小时。根据其值得注意的临床前数据，有8项药物已进入人体临床试验，并顺利通过了1期研究。
• Cyclic oxyguanidine pyrazinones as protease inhibitors
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20020052357A1

  公开（公告）日：2002-05-02

  Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: 1 wherein R 3 , R 4 , R 5 , W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi.

  本文描述了环状氧胍吡唑酮化合物，包括公式I中的化合物：其中R3、R4、R5、W和A如规范中所述，以及其水合物、溶剂化物或药学上可接受的盐。本发明的化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，如凝血酶、胰蛋白酶、血栓素、纤溶酶和Xa因子。其中某些化合物通过直接选择性抑制凝血酶表现出抗血栓活性。本文还描述了用于抑制血小板丢失、抑制血小板聚集形成、抑制纤维蛋白形成、抑制血栓形成和抑制栓塞形成的组合物。本发明化合物的其他用途是作为抗凝剂嵌入或物理连接到用于血液收集、血液循环和血液储存的器械制造材料中，例如导管、血液透析机、血液采集注射器和管道、血管支架。此外，这些化合物可以被检测标记并用于体内血栓的成像。