7-(3-Carboxypiperazin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid | 861391-60-8

• 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: 7-(3-Carboxypiperazin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid
• 英文别名: 7-(3-carboxypiperazin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid
• CAS: 861391-60-8
• 化学式: C₁₉H₂₀FN₃O₆
• 分子量: 405.383
• InChiKey: DHQKMDASURGTBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  ethyl 3-(cyclopropylamino)-2-(2,4,5-trifluoro-3-methoxybenzoyl)acrylate 在 三氟化硼乙醚 、 potassium carbonate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 77.0h， 生成 7-(3-Carboxypiperazin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of gatifloxacin derivatives and their biological activities against Mycobacterium leprae and Mycobacterium tuberculosis

  摘要：

  Novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by H-1, C-13 and F-19 NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R-8 and a secondary carbamate in R-3') and compound 5 (with a hydrogen in R-8 and an ethyl ester in R-3') displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R-3' substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.011

文献信息

• [EN] RIFAMYCIN IMINO DERIVATIVES EFFECTIVE AGAINST DRUG-RESISTANT MICROBES<br/>[FR] DERIVES DE RIFAMYCINE IMINO EFFICACES CONTRES DES MICROBES PHARMACORESISTANTS
  申请人：CUMBRE INC

  公开号：WO2005070941A1

  公开（公告）日：2005-08-04

  The present invention relates to rifamycin 3-iminomethylenyl (-CH=N-) derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. The claimed rifamycin derivative has a rifamycin moiety covalently linked to a linker through an iminomethylenyl (-CH=N-) group at the C-3 carbon of the rifamycin moiety and the linker is, in turn, covalently linked to a quinolone structure or its pharmacophore within the DNA gyrase and topoisomerase IV inhibitor family. The inventive rifamycins are novel and exhibit activity against both rifampin and ciprofloxacin-resistant microorganisms.

  本发明涉及具有抗微生物活性的利福霉素3-亚甲基亚胺基(-CH=N-)衍生物，包括对耐药微生物的活性。所述的利福霉素衍生物具有一个利福霉素基团，通过亚甲基亚胺基(-CH=N-)在利福霉素基团的C-3碳上与一个连接剂共价连接，而连接剂又与DNA旋转酶和拓扑异构酶IV抑制剂家族中的奎诺酮结构或其药效团共价连接。这种创新的利福霉素是新颖的，并对利福平和环丙沙星耐药微生物表现出活性。
• Rifamycin imino derivatives effective against drug-resistant microbes
  申请人：Ding Z. Charles

  公开号：US20050209210A1

  公开（公告）日：2005-09-22

  The present invention relates to rifamycin 3-iminomethylenyl (—CH═N—) derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. The claimed rifamycin derivative has a rifamycin moiety covalently linked to a linker through an iminomethylenyl (—CH═N—) group at the C-3 carbon of the rifamycin moiety and the linker is, in turn, covalently linked to a quinolone structure or its pharmacophore within the DNA gyrase and topoisomerase IV inhibitor family. The inventive rifamycins are novel and exhibit activity against both rifampin and ciprofloxacin-resistant microorganisms.

  本发明涉及具有抗微生物活性的利福霉素3-亚甲基亚胺基(—CH═N—)衍生物，包括对耐药微生物的活性。所述利福霉素衍生物具有利福霉素基团通过亚甲基亚胺基(—CH═N—)与连接基团共价连接于利福霉素基团的C-3碳，并且连接基团与DNA酶解酶和拓扑异构酶IV抑制剂家族中的喹诺酮结构或其药效团共价连接。本发明的利福霉素是新颖的，并且对利福平和环丙沙星耐药微生物均有活性。
• RIFAMYCIN IMINO DERIVATIVES EFFECTIVE AGAINST DRUG-RESISTANT MICROBES
  申请人：Cumbre Pharmaceuticals Inc.

  公开号：EP1723150A1

  公开（公告）日：2006-11-22
• US7238694B2
  申请人：——

  公开号：US7238694B2

  公开（公告）日：2007-07-03
• Synthesis of gatifloxacin derivatives and their biological activities against Mycobacterium leprae and Mycobacterium tuberculosis
  作者：Catherine Gomez、Prishila Ponien、Nawal Serradji、Aazdine Lamouri、Alix Pantel、Estelle Capton、Vincent Jarlier、Guillaume Anquetin、Alexandra Aubry

  DOI：10.1016/j.bmc.2012.12.011

  日期：2013.2

  Novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by H-1, C-13 and F-19 NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R-8 and a secondary carbamate in R-3') and compound 5 (with a hydrogen in R-8 and an ethyl ester in R-3') displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R-3' substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. (C) 2012 Elsevier Ltd. All rights reserved.