(E)-1-cyclopropyl-6-fluoro-7-(8-(methoxyimino)-2,6-diazaspiro[3.4]octan-6-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid | 219680-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (E)-1-cyclopropyl-6-fluoro-7-(8-(methoxyimino)-2,6-diazaspiro[3.4]octan-6-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• 英文别名: 1-cyclopropyl-6-fluoro-7-[(8E)-8-methoxyimino-2,6-diazaspiro[3.4]octan-6-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 219680-11-2
• 化学式: C₁₉H₂₀FN₅O₄
• 分子量: 401.4
• InChiKey: ZNPOCLHDJCAZAH-UCQKPKSFSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  10

制备方法与用途

生物活性

Zabofloxacin (DW-224a Free base) 是一种有效的抑制剂，对细菌 II 型和 IV 型拓扑异构酶具有良好的抑制作用。它对革兰氏阳性致病菌如金黄色葡萄球菌、化脓性链球菌和肺炎链球菌展现出优秀的抗菌活性。Zabofloxacin 属于新型氟萘啶酮喹诺酮类抗生素，被认为是研究喹诺酮易感 (QSSP) 和喹诺酮耐药淋病 (QRSP) 的替代试剂。

靶点

• Topoisomerase I
• Topoisomerase II

体外研究

Zabofloxacin 在体外对青霉素敏感的肺炎链球菌（最小抑制浓度，MIC₉₀：0.03 mg/L）和青霉素耐药的肺炎链球菌（MIC₉₀：0.03 mg/L）表现出极高的活性。在对抗喹诺酮耐药的肺炎链球菌方面，Zabofloxacin (MIC₉₀：1 mg/L) 比环丙沙星、SParfloxacin 和莫西沙星更为有效。

文献信息

• [EN] AN IMPROVED MANUFACTURING METHOD OF ZABOFLOXACIN<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE ZABOFLOXACINE
  申请人：DONG WHA PHARM CO LTD

  公开号：WO2015178663A1

  公开（公告）日：2015-11-26

  The present invention provides an improved method of manufacturing Zabofloxacin D-aspartate. The present invention provides a novel method of manufacturing 8-methoxyimino-2,6-diaza-spiro[3,4]octane-2-carboxylic acid t-butyl ester succinate (TBDCS) or 2-(2,2,2-trifluoro-acetyl)-2,6-diaza-spiro[3,4]octan-8-one O-methyloxime methanesulfonate (TDMOS), which are separately the starting materials for manufacturing Zabofloxacin D-aspartate. The manufacturing method according to the present invention is suitable for mass production of Zabofloxacin D-aspartate for it enables manufacturing in high yield and high quality (HPLC purity ≥ 99.5%) as well as reducing the unit cost of production by using only 1.0~1.1 equivalents of TBDCS or TDMOS in a substitution reaction.

  本发明提供了一种改进的制备左氨糖基左氨基脲酸扎博氟沙星的方法。本发明提供了一种制备8-甲氧基亚胺-2,6-二氮杂螺[3,4]辛-2-羧酸叔丁酯琥珀酸盐（TBDCS）或2-(2,2,2-三氟乙酰)-2,6-二氮杂螺[3,4]辛-8-酮O-甲氧基肟甲磺酸盐（TDMOS）的新方法，它们分别是制备左氨糖基左氨基脲酸扎博氟沙星的起始原料。根据本发明的制备方法适用于大规模生产左氨糖基左氨基脲酸扎博氟沙星，因为它能够以高产率和高质量（HPLC纯度≥99.5%）进行制备，同时通过在取代反应中仅使用1.0~1.1当量的TBDCS或TDMOS来降低生产成本。
• [EN] QUINOLONE CARBOXYLIC ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDE QUINOLONECARBOXYLIQUE
  申请人：DONG WHA PHARMACEUTICAL INDUSTRIAL CO., LTD.

  公开号：WO1999000393A1

  公开（公告）日：1999-01-07

  (EN) The present invention relates to quinolonecarboxylic acid derivatives having more excellent and broad antibacterial activities than the existing quinolone-series antibiotics. More specifically, it pertains to novel quinolonecarboxylic acid derivatives represented by formula (1), which have a derivative of 7-[8-(alcoxyimino)-2,6-diazaspiro[3,4]oct-6-yl] as a substituent, and pharmaceutically acceptable salts and isomers thereof; wherein A is C-H, C-F, C-Cl, C-O-CH3 or N; Y is H or amino; R1 is cyclopropyl or 2,4-difluorophenyl; R2 is C1-4 alkyl; and R3 is H or C1-4 alkyl.(FR) L'invention concerne des dérivés d'acide quinolonecarboxylique ayant une action antibactérienne étendue, excellente et améliorée par rapport aux antibiotiques existants de la série quinolone. Plus spécifiquement, l'invention concerne de nouveaux dérivés d'acide quinolonecarboxylique représentés par la formule générale (1), et possédant un dérivé de 7-[8-(alcoxyimino)-2,6-diazaspiro[3,4]oct-6-yl] comme substituant, ainsi que les sels pharmaceutiquement acceptables et les isomères de ces produits. Dans ladite formule, A est C-H, C-F, C-Cl, C-O-CH3 ou N; Y est H ou amino; R1 est cyclopropyle ou 2,4-difluorophényle; R2 est alkyle C1-4; et R3 est H ou alkyle C1-4.

  (中) 本发明涉及一种比现有喹诺酮系列抗生素具有更优异和广泛的抗菌活性的喹诺酮羧酸衍生物。更具体地，它涉及由式（1）表示的新型喹诺酮羧酸衍生物，其中具有7- [8-（醇氧基亚胺）-2,6-二氮杂螺[3,4]辛-6-基]的衍生物作为取代基，以及其药学上可接受的盐和异构体；其中A为C-H，C-F，C-Cl，C-O-CH3或N；Y为H或氨基；R1为环丙基或2,4-二氟苯基；R2为C1-4烷基；R3为H或C1-4烷基。
• Quinolone carboxylic acid derivatives
  申请人：Dong Wha Pharmaceutical Industrial Co., Ltd.

  公开号：US20020035258A1

  公开（公告）日：2002-03-21

  The present invention relates to quinolonecarboxylic acid derivatives having more excellent and broad antibacterial activities than the existing quinolone-series antibiotic. More specifically, it pertains to novel quinolonecarboxyllic acid derivative represented by following formula 1, which have a derivative of 7-[8-(alkoxyimino)-2,6-diazaspiro[3.4]oct-6-yl] as a substituent, and pharmaceutically acceptable salts and isomers thereof: 1 Wherein A is C—H, C—F, C—C1, C—O—CH3 or amino; R1 is cyclopropyl or 2,4-difluorsophenyl R2 is C1—4 alkyl; and C3 is H or C1-4 alkyl.

  本发明涉及喹诺酸衍生物，其具有比现有喹诺系抗生素更优异和广泛的抗菌活性。更具体地说，它涉及由以下式1表示的新型喹诺酸衍生物，其具有7-[8-(alkoxyimino)-2,6-diazaspiro[3.4]oct-6-yl]衍生物作为取代基，以及其药学上可接受的盐和同分异构体：1其中A是C-H、C-F、C-Cl、C-O-CH3或氨基；R1是环丙基或2,4-二氟苯基；R2是C1-4烷基；C3是氢或C1-4烷基。
• ASPARTATE OF 1-CYCLOPROPYL-6-FLUORO-7-(8-METHOXYIMINO-2,6-DIAZA-SPIRO[3.4]OCT-6-YL)-4-OXO-1,4-DIHYDRO-[1,8]NAPHTHYRIDINE-3-CARBOXYLIC ACID, METHOD FOR PREPARING THE SAME, AND ANTIMICROBIAL PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Ryu Jei Man

  公开号：US20100184795A1

  公开（公告）日：2010-07-22

  Disclosed are aspartic acid salts of 1-cyclopropyl-6-fluoro-7-(8-methoxyimino-2,6-diaza-spiro[3.4]oct-6-yl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid, methods for preparing the same, and antimicrobial pharmaceutical compositions comprising the same.

  本发明涉及天冬氨酸盐的1-环丙基-6-氟-7-(8-甲氧基亚胺基-2,6-二氮杂螺[3.4]辛-6-基)-4-氧代-1,4-二氢-[1,8]萘啶-3-羧酸，其制备方法，以及包含它们的抗微生物制剂。
• Polymer conjugate comprising a bioactive agent
  申请人：POLYACTIVA PTY LTD

  公开号：US10758626B2

  公开（公告）日：2020-09-01

  The present invention relates in general to polymer-bioactive agent conjugates for delivering a bioactive agent to a subject. The polymer-bioactive agent conjugates contain triazole moieties in the polymer backbone and a bioactive moiety selected from quinolones, NSAIDs and mixtures thereof. The present invention also relates to methods for preparing the polymer conjugates using click cycloaddition chemical reactions, to monomer-bioactive agent conjugates suitable for preparing the polymer conjugates, and to pharmaceutical products comprising the polymer conjugates for the post-surgical care to treat or prevent infections, provide analgesia and treat inflammation.

  本发明总体上涉及用于向受试者输送生物活性剂的聚合物-生物活性剂共轭物。聚合物-生物活性剂共轭物的聚合物骨架中含有三唑分子和选自喹诺酮类、非甾体抗炎药及其混合物的生物活性分子。本发明还涉及使用单击环化化学反应制备聚合物共轭物的方法、适用于制备聚合物共轭物的单体-生物活性剂共轭物，以及包含聚合物共轭物的用于手术后治疗或预防感染、提供镇痛和治疗炎症的药物产品。