DX-619 | 431058-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: DX-619
• 英文别名: 3-Quinolinecarboxylic acid, 7-((3R)-3-(1-aminocyclopropyl)-1-pyrrolidinyl)-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-8-methoxy-4-oxo-；7-[(3R)-3-(1-aminocyclopropyl)pyrrolidin-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylic acid
• CAS: 431058-65-0
• 化学式: C₂₁H₂₄FN₃O₄
• 分子量: 401.438
• InChiKey: ZLICIITZJTYKAQ-DIOULYMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  DX-619 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以83%的产率得到7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl]-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

  摘要：

  A series of novel 6-desfluoro [des-F(6)] and 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methoxyquinolones bearing 3-(1-aminocycloalkyl)pyrrolidin-1-yl substituents at the C-7 position (1-6) was synthesized to obtain potent drugs for nosocomial infections caused by Gram-positive pathogens. The des-F(6) compounds 4-6 exhibited at least four times more potent activity against representative Gram-positive bacteria than ciprofloxacin or moxifloxacin. Among the derivatives, 7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl] derivative 4, which showed favorable profiles in preliminary toxicological and non-clinical pharmacokinetic studies, exhibited potent antibacterial activity against clinically isolated Gram-positive pathogens that had become resistant to one or more antibiotics. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.026
• 作为产物：
  描述：

  (3R)-3-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-5-oxo-1-[(S)-1-phenylethyl]pyrrolidine 在 钯 盐酸 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 13.0h， 生成 DX-619
  参考文献：
  名称：

  DEHALOGENO COMPOUNDS

  摘要：

  公开号：

  EP1336611B1

文献信息

• Dehalogeno compounds
  申请人：——

  公开号：US20040063754A1

  公开（公告）日：2004-04-01

  3-(1-Aminocycloalkyl)pyrrolidinyl-substituted-6-dehalodeno(hydrogen-substituted)quinolon carboxylic acid derivatives having specific substitunets as represented by the following formula (I), its salts, and hydrates thereof exhibit a broad and potent antibacterial activity on gram-negative and gram-positive bacteria, in particular, resistant bacteria typified by gram-positive cocci, including MRSA, PRSP and VRE. Thus these compounds are usable as drugs. 1

  具有特定取代基的3-(1-氨基环烷基)吡咯烷基取代的6-去卤代(氢取代)喹诺酮羧酸衍生物及其盐和水合物，如下式(I)所示，表现出广谱和强效的抗菌活性，对革兰氏阴性菌和革兰氏阳性菌均有效，特别是对革兰氏阳性球菌等耐药菌，包括MRSA、PRSP和VRE有良好的抗菌活性。因此这些化合物可用作药物。
• INTERMEDIATES FOR THE PRODUCTION OF OPTICALLY ACTIVE CYCLOPROPYLAMINE DERIVATIVES AND PROCESS FOR THE PRODUCTION OF THE INTERMEDIATES
  申请人：FUJITA Masao

  公开号：US20090240066A1

  公开（公告）日：2009-09-24

  The present invention provides intermediates needed for production of an optically active compound represented by formula (6), which enable the compound (6) to be readily synthesized in simple production steps without optical resolution, and also provides a process for producing the intermediates. A process for producing an optically active compound represented by formula (4): wherein R 1 represents a protecting group for the amino group, or a salt thereof, characterized in that a reagent prepared from an titanium(IV) reagent and an alkylmetal compound is reacted with an optically active compound represented by formula (3): wherein R 1 has the same meaning as defined above, if needed, in the presence of a Lewis acid.

  本发明提供了制备光学活性化合物(6)所需的中间体，使得化合物(6)可以在简单的生产步骤中无需光学分辨就能轻松合成，并提供了制备该中间体的方法。一种制备由公式(4)表示的光学活性化合物的方法：其中R1代表氨基的保护基或其盐，其特征在于将由钛(IV)试剂和烷基金属化合物制备的试剂与由公式(3)表示的光学活性化合物反应，其中R1具有与上述定义相同的含义，必要时在路易斯酸的存在下。
• Dehalogeno-compounds
  申请人：Takahashi Hisashi

  公开号：US20070123560A1

  公开（公告）日：2007-05-31

  3-(1-Aminocycloalkyl)pyrrolidinyl-substituted-6-dehalodeno(hydrogen-substituted)quinolon carboxylic acid derivatives having specific substituents as represented by the following formula (I), its salts, and hydrates thereof exhibit a broad and potent antibacterial activity on gram-negative and gram-positive bacteria, in particular, resistant bacteria typified by gram-positive cocci, including MRSA, PRSP and VRE. Thus these compounds are usable as drugs.

  具有特定取代基的3-(1-氨基环烷基)吡咯烷基取代的6-去卤代（氢取代）喹诺酮羧酸衍生物，其盐和水合物，如以下公式（I）所示，表现出广谱和强效的抗菌活性，对革兰氏阴性和革兰氏阳性细菌均有效，特别是对革兰氏阳性球菌等耐药菌，包括MRSA、PRSP和VRE。因此，这些化合物可用作药物。
• Method for Production of Quinolone-Containing Lyophilized Preparation
  申请人：Nishimoto Norihiro

  公开号：US20080300403A1

  公开（公告）日：2008-12-04

  The present invention is directed to a lyophilized preparation which contains a synthetic quinolone antibacterial compound and, as a solo additive, a pH-adjusting agent, and which exhibits an excellent reconstituting property. The invention provides a method for producing a lyophilized preparation containing a synthetic quinolone antibacterial compound as an active ingredient, characterized by including, sequentially, cooling an aqueous solution containing a synthetic quinolone antibacterial compound and a pH-adjusting agent to yield a frozen product, elevating the temperature of the frozen product, and re-cooling the resultant to prepare the lyophilized preparation.

  本发明涉及一种冻干制剂，其包含合成喹诺酮类抗菌化合物和一个pH调节剂作为单一添加剂，并表现出优异的重构性能。本发明提供了一种制备含有合成喹诺酮类抗菌化合物作为活性成分的冻干制剂的方法，其特征在于依次包括将含有合成喹诺酮类抗菌化合物和pH调节剂的水溶液冷却以产生冻结产物，提高冻结产物的温度，然后再次冷却以制备冻干制剂。
• Quinolone-containing medicinal composition
  申请人：Yano Emi

  公开号：US20090117205A1

  公开（公告）日：2009-05-07

  The present invention relates to a pharmaceutical solution comprising the following components (A) and (B): (A) a compound represented by the following formula (1): or a salt thereof, or a hydrate thereof; and (B) a multivalent metal compound, wherein molar ratio of the component (B) to component (A) (the multivalent compound/component (B)) is 0.01 to 0.7. A pharmaceutical solution adapted for intravascular administration containing the quinolone compound at a therapeutically sufficient amount is provided, and this solution exhibits reduced toxicity even when the multivalent metal compound were incorporated at a reduced amount.

  本发明涉及一种药物溶液，包括以下组分(A)和(B)：(A)表示为以下式子（1）的化合物：或其盐、或其水合物；以及(B)多价金属化合物，其中组分(B)与组分(A)的摩尔比（多价化合物/组分(B)）为0.01至0.7。提供一种适用于静脉内给药的药物溶液，其中含有治疗上足够量的喹诺酮化合物，并且即使将多价金属化合物掺入量降低，该溶液仍表现出降低的毒性。