(3-Benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)acetic acid | 147269-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3-Benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)acetic acid
• 英文别名: 3-benzyloxycarbonylamino-6-methyl-1-methylenecarboxy-2-pyridinone；3-benzyloxycarbonylamino-6-methyl-1-carboxymethyl-2-pyridinone；2-[6-methyl-2-oxo-3-(benzyloxycarbonylamino)-2H-pyridin-1-yl]acetic acid；3-(benzyloxycarbonyl)amino-6-methyl-1-carboxymethyl-2-pyridinone；2-[6-methyl-2-oxo-3-(phenylmethoxycarbonylamino)pyridin-1-yl]acetic acid
• CAS: 147269-63-4
• 化学式: C₁₆H₁₆N₂O₅
• 分子量: 316.313
• InChiKey: KSIZSWMDKITEMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-Benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)acetic acid 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.33h， 生成 2-[2-(3-amino-6-methyl-2-oxopyridin-1(2H)-yl)acetylamino]-3-methylpentanoic acid (1-carbamoyl-2-hydroxypropyl)amide
  参考文献：
  名称：

  含有氨基酸模拟片段的分子钳：野生型和突变的HIV-1蛋白酶二聚化的新抑制剂。

  摘要：

  我们已经设计，合成和评估了基于萘基支架的新型拟肽分子钳的抑制活性和代谢稳定性，以抑制HIV-1蛋白酶的二聚作用。将拟肽基序插入一条肽链中，使其对蛋白水解具有抗性。可以降低分子钳的肽特性，而无需改变它们抑制二聚化的方式。突变的HIV-1蛋白酶也容易受到二聚化抑制剂的影响，与野生型蛋白酶相比，多突变的蛋白酶ANAM-11对抑制剂的敏感性是其两倍。因此，可以在不损害抗二聚体分子钳体外抑制野生型和突变的HIV-1蛋白酶的能力的情况下提高抗二聚体分子钳的代谢稳定性。

  DOI：

  10.1021/jm060576k
• 作为产物：
  描述：

  3-氰基-6-甲基-2(1H)-吡啶酮 在 sodium hydroxide 、 叠氮磷酸二苯酯 、 氢溴酸 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 生成 (3-Benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)acetic acid
  参考文献：
  名称：

  PYRIDONE-BASED PEPTIDOMIMETIC INHIBITORS OF INTERLEUKIN-1β-CONVERTING ENZYME (ICE)

  摘要：

  New potent, reversible inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P-2-P-3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00220-5

文献信息

• Heterocyclic amides
  申请人：Zeneca Limited

  公开号：US05521179A1

  公开（公告）日：1996-05-28

  The present invention relates to certain novel heterocyclic amides which are 1-pyridylacetamide compounds of formula I, set out herein, which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes intermediates useful in the synthesis of these heterocyclic amides, processes for preparing the heterocyclic amides, pharmaceutical compositions containing such heterocyclic amides and methods for their use.

  本发明涉及某些新颖的杂环酰胺，它们是式I所示的1-吡啶乙酰胺化合物，这些化合物是人类白细胞弹性蛋白酶（HLE）的抑制剂，也被称为人类中性粒细胞弹性蛋白酶（HNE），使它们在需要这种抑制作用时非常有用，例如用作药理学、诊断和相关研究工具以及治疗哺乳动物中HLE相关疾病。该发明还包括在合成这些杂环酰胺过程中有用的中间体，制备这些杂环酰胺的方法，含有这些杂环酰胺的药物组合物以及它们的使用方法。
• Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US06350764B2

  公开（公告）日：2002-02-26

  Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9 and Het, R1, R7, R8, R12-R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. 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. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. 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.

  描述了氨基胍和烷氧基胍化合物，包括式VII的化合物： 其中X为O或NR9，Het，R1，R7，R8，R12-R15，Ra，Rb，Rc，Z和n在说明书中列出，以及其水合物，溶剂合物或药学上可接受的盐，其抑制蛋白酶如凝血酶。还描述了制备这种化合物的方法。该发明的化合物是蛋白酶的有效抑制剂，特别是类似胰蛋白酶的丝氨酸蛋白酶，如胰蛋白酶、凝血酶、纤溶酶和Xa因子。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。该发明包括一种用于在哺乳动物中抑制血小板丢失、抑制血小板聚集物形成、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，包括一种该发明的化合物在药学上可接受的载体中。该发明的化合物的其他用途是作为抗凝剂，嵌入或物理上连接到用于血液采集、血液循环和血液储存设备的材料中，如导管、血液透析机、血液采集注射器和管道、血管内支架。此外，这些化合物可以被检测标记并用于体内血栓的成像。
• Inhibitors of interleukin-1 beta converting enzyme
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20020099042A1

  公开（公告）日：2002-07-25

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

  本发明涉及一种新型化合物类别，其为白细胞介素-1β转化酶抑制剂。本发明的ICE抑制剂具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制ICE活性，因此可以优势地用作对白细胞介素-1介导的疾病，包括炎症性疾病、自身免疫疾病和神经退行性疾病的治疗剂。本发明还涉及使用本发明的化合物和组合物抑制ICE活性的方法和治疗白细胞介素-1介导疾病的方法。
• Heteroaryl aminoguanidine and alkoxyguanidines and their use as protease inhibitors
  申请人：Lu Tianbao

  公开号：US20060211719A1

  公开（公告）日：2006-09-21

  Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR 9 and Het, R 1 , R 7 , R 8 , R 12 -R 15 , R a , R b , R c , Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. 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. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. 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.

  本文描述了氨基胍和烷氧基胍类化合物，包括式VII的化合物：其中X为O或NR9，Het、R1、R7、R8、R12-R15、Ra、Rb、Rc、Z和n在规范中列出，以及其水合物、溶剂化合物或药学上可接受的盐，可抑制蛋白酶，如凝血酶。还描述了制备这种化合物的方法。该发明的化合物是蛋白酶的有效抑制剂，特别是类胰蛋白酶的丝氨酸蛋白酶，如胰蛋白酶、凝血酶、纤溶酶和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作用。该发明包括一种组合物，用于抑制哺乳动物中的血小板丢失、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，其包括该发明的化合物和药学上可接受的载体。该发明的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采集、血液循环和血液储存的器械的制造材料中，如导管、血液透析机、血液采集注射器和管子、血液管路和支架。此外，这些化合物可以被标记并用于体内血栓的成像。
• Integrin antagonists
  申请人：Merck & Co., Inc.

  公开号：US06211184B1

  公开（公告）日：2001-04-03

  This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as vitronectin receptor antagonists. The vitronectin receptor antagonist compounds of the present invention are &agr;v&bgr;3 antagonists, &agr;v&bgr;5 antagonists or dual &agr;v&bgr;3/&agr;v&bgr;5 antagonists useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation and tumor growth.

  本发明涉及某些新型化合物及其衍生物，它们的合成以及它们作为vitronectin受体拮抗剂的用途。本发明的vitronectin受体拮抗剂化合物是αvβ3拮抗剂、αvβ5拮抗剂或双重αvβ3/αvβ5拮抗剂，可用于抑制骨吸收、治疗和预防骨质疏松症，并抑制再狭窄、糖尿病视网膜病变、黄斑变性、血管生成、动脉粥样硬化、炎症和肿瘤生长。