[[2-[(2-hydroxypropyl)amino]-1,2-dioxoethyl]amino]acetic acid ethyl ester | 221136-49-8

• 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: [[2-[(2-hydroxypropyl)amino]-1,2-dioxoethyl]amino]acetic acid ethyl ester
• 英文别名: N-(Ethoxycarbonylmethyl)-N'-(2-hydroxy-1-propyl) oxamide；Ethyl (2-((2-hydroxypropyl)amino)-2-oxoacetyl)glycinate；ethyl 2-[[2-(2-hydroxypropylamino)-2-oxoacetyl]amino]acetate
• CAS: 221136-49-8
• 化学式: C₉H₁₆N₂O₅
• 分子量: 232.236
• InChiKey: FDFGBFGTDSIZPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [[2-[(2-hydroxypropyl)amino]-1,2-dioxoethyl]amino]acetic acid ethyl ester 在 ruthenium trichloride 、 lithium hydroxide 、 ammonium hydroxide 、 sodium bromate 、 三乙胺 、 三氟乙酸 、 三氟乙酸酐 、 三溴氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 N-(2-Amino-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 、 异丙醇胺 以 乙醇 为溶剂， 以97%的产率得到[[2-[(2-hydroxypropyl)amino]-1,2-dioxoethyl]amino]acetic acid ethyl ester
  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

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020035115A1

  公开（公告）日：2002-03-21

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1

  本发明的化合物具有以下结构，可用于抑制凝血酶和相关的血栓闭塞：1。
• 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。
• Pyrazinone thrombin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06011038A1

  公开（公告）日：2000-01-04

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: ##STR1## for example: ##STR2##

  本发明的化合物可用于抑制凝血酶和相关的血栓闭塞，其具有以下结构：##STR1##例如：##STR2##
• Aminoalkyl-pyrazinones and-pyridones as thrombin inhibitors
  申请人：Feurer Achim

  公开号：US20070099927A1

  公开（公告）日：2007-05-03

  The invention relates to compounds of formula (I) wherein A, B, X, R 1 , R 2 , G, R 3 , 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.

  本发明涉及式(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。本发明还涉及其制备和用作药物的用途。
• Kilogram Scale Synthesis of the Pyrazinone Acetic Acid Core of an Orally Efficacious Thrombin Inhibitor
  作者：Fred J. Fleitz、Terry A. Lyle、Nan Zheng、Joseph D. Armstrong、R. P. Volante

  DOI：10.1080/00397910008086927

  日期：2000.9

  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.