3-(2-phenethylamino)-5-chloro-6-methyl-1-benzyloxycarbonylmethylpyrazinone | 199296-27-0

• 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: 3-(2-phenethylamino)-5-chloro-6-methyl-1-benzyloxycarbonylmethylpyrazinone
• 英文别名: (5-chloro-6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)acetic acid benzyl ester；benzyl 2-[3-chloro-2-methyl-6-oxo-5-(2-phenylethylamino)pyrazin-1-yl]acetate
• CAS: 199296-27-0
• 化学式: C₂₂H₂₂ClN₃O₃
• 分子量: 411.888
• InChiKey: HMOIFVSWQQGUOG-UHFFFAOYSA-N

物化性质

• 沸点：
  546.2±60.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-phenethylamino)-5-chloro-6-methyl-1-benzyloxycarbonylmethylpyrazinone 在 palladium on activated charcoal N-甲基吗啉 、 氢氧化钾 、 lithium hydroxide 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide
  参考文献：
  名称：

  Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates

  摘要：

  We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.

  DOI：

  10.1021/jm980368v
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 以 二氯甲烷 、 乙酸乙酯 、 邻二氯苯 为溶剂， 生成 3-(2-phenethylamino)-5-chloro-6-methyl-1-benzyloxycarbonylmethylpyrazinone
  参考文献：
  名称：

  肥大细胞类胰蛋白酶的新型吡嗪酮抑制剂：合成和SAR评价。

  摘要：

  在此手稿中，描述了新型吡嗪酮类的类胰蛋白酶抑制剂的合成和SAR评估。P1和P4基团的化学优化导致鉴定出7p（K（i）= 93 nM）作为肥大细胞类胰蛋白酶的有效抑制剂。

  DOI：

  10.1016/j.bmcl.2004.07.051

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。
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：MERCK & CO., INC.

  公开号：WO1998042342A1

  公开（公告）日：1998-10-01

  (EN) A compound which inhibits human thrombin and has structure (I) or (II) or (III) and pharmaceutically acceptable salts thereof, wherein compounds such as (IV) are useful for inhibiting formation of blood platelet aggregates in blood in a mammal.(FR) L'invention concerne un composé inhibant la thrombine humaine et ayant la structure (I) ou (II) ou (III), ainsi que des sels pharmaceutiquement acceptables dudit composé (IV), caractérisé en ce que des composés tels que sont utiles pour inhiber la formation d'agrégats de plaquettes dans le sang d'un mammifère.

  一种抑制人类凝血酶并具有结构（I）或（II）或（III）及其药物可接受的盐的化合物，其中类似（IV）的化合物对于抑制哺乳动物血液中血小板聚集的形成是有用的。
• Thromboresistant materials incorporating pyrazinone protease inhibitors
  申请人：——

  公开号：US20010021713A1

  公开（公告）日：2001-09-13

  Thromboresistant materials are described which incorporate pyrazinone compounds of the Formula I: 1 wherein X is O, NR 11 or CH=N, R 3 -R 11 , R a , R b , R c , W, m, and n are 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.

  本发明提供了一种含有Formula I的吡唑酮化合物的抗血栓材料：1其中X为O、NR11或CH= N，R3-R11、Ra、Rb、Rc、W、m和n在规范中设置，以及其水合物、溶剂化合物或药学上可接受的盐。本发明的化合物是蛋白酶的强效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，如凝血酶、血纤维蛋白溶解酶和Xa因子。其中某些化合物通过直接、选择性地抑制凝血酶表现出抗血栓活性。本发明还描述了用于抑制血小板损失、抑制血小板聚集、抑制纤维蛋白形成、抑制血栓形成和抑制栓子形成的组合物。本发明的化合物的其他用途是作为抗凝剂嵌入或物理链接到用于血液收集、血液循环和血液储存的设备中，如导管、血液透析机、血液采集注射器和管道、血管支架等。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：EP0900207B1

  公开（公告）日：2001-11-21
• Non-covalent thrombin inhibitors featuring p 3 -heterocycles with P 1 -monocyclic arginine surrogates
  作者：John E Reiner、Daniel V Siev、Gian-Luca Araldi、Jingrong Jean Cui、Jonathan Z Ho、Komandla Malla Reddy、Lala Mamedova、Phong H Vu、Kuen-Shan S Lee、Nathaniel K Minami、Tony S Gibson、Susanne M Anderson、Annette E Bradbury、Thomas G Nolan、J.Edward Semple

  DOI：10.1016/s0960-894x(02)00129-4

  日期：2002.4

  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.