7-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 937251-32-6

• 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-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-(3-aminomethyl-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid；7-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid；7-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid
• CAS: 937251-32-6
• 化学式: C₁₉H₂₂FN₃O₄
• 分子量: 375.4
• InChiKey: LEZKBUPOVDJOKP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  7-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 丙烯腈 在 三乙胺 作用下， 以 甲醇 为溶剂， 生成 7-{3-[(2-cyano-ethylamino)-methyl]-pyrrolidin-1-yl}-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  新型含腈氟喹诺酮类抗菌剂的合成及生物学评价。

  摘要：

  据报道，几种新的含弱碱性胺类的含腈氟喹诺酮类药物具有减少的hERG（人醚-go-go-go基因）通道抑制作用的潜力，如多芬替利试验所测。新的氟喹诺酮类药物对革兰氏阳性和革兰氏阴性菌株均有效，包括耐甲氧西林的金黄色葡萄球菌和耐氟喹诺酮的肺炎链球菌。通过克隆形成性测试，几种类似物还显示出较低的人类遗传毒性潜力。具有良好的体外活性和体外安全性的化合物22和37（分别命名为PF-00951966和PF-02298732）在大鼠中也显示出良好的药代动力学特性。

  DOI：

  10.1016/j.bmcl.2007.01.090
• 作为产物：
  描述：

  7-[3-(tert-butoxycarbonylamino-methyl)-pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid difluoroborate ester 在 盐酸 、 乙醇 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 7-[(3S)-3-(aminomethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  新型含腈氟喹诺酮类抗菌剂的合成及生物学评价。

  摘要：

  据报道，几种新的含弱碱性胺类的含腈氟喹诺酮类药物具有减少的hERG（人醚-go-go-go基因）通道抑制作用的潜力，如多芬替利试验所测。新的氟喹诺酮类药物对革兰氏阳性和革兰氏阴性菌株均有效，包括耐甲氧西林的金黄色葡萄球菌和耐氟喹诺酮的肺炎链球菌。通过克隆形成性测试，几种类似物还显示出较低的人类遗传毒性潜力。具有良好的体外活性和体外安全性的化合物22和37（分别命名为PF-00951966和PF-02298732）在大鼠中也显示出良好的药代动力学特性。

  DOI：

  10.1016/j.bmcl.2007.01.090

文献信息

• [EN] QUINOLONE ANTIBACTERIAL AGENTS<br/>[FR] AGENTS ANTIBACTERIENS A LA QUINOLONE
  申请人：WARNER LAMBERT CO

  公开号：WO2005049602A1

  公开（公告）日：2005-06-02

  Compounds of formula (I) wherein A is formula (II), formula (III) or formula (IV), and B is formula (V), formula (VI), or formula (VII), can be used in a variety of applications including use as antibacterial agents.

  式(I)的化合物中，其中A是式(II)，式(III)或式(IV)，B是式(V)，式(VI)或式(VII)，可用于各种应用，包括用作抗菌剂。
• Multi-tiered, high through-put screen for compounds effective against bacterial biofilm compounds effective for inhibiting and eradicating bacterial biofilm
  申请人：University of Cincinnati

  公开号：US10202631B2

  公开（公告）日：2019-02-12

  A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include as says for total bacterial growth, bacterial metabolic activity, and biofilm formation.

  本发明公开了一种高通量筛选方法，用于确定可有效抑制生物膜形成和/或杀死已形成的生物膜的制剂。该方法包括三个层级，每个层级包括三个特定的生物过程检测。层级为初筛、确认筛和剂量反应筛，生物过程测定包括细菌生长总量、细菌代谢活性和生物膜形成。
• Multi-tiered high through-put screen for compounds effective against bacterial biofilm and compounds effective for inhibiting and eradicating bacterial biofilm
  申请人：University of Cincinnati

  公开号：US10704076B2

  公开（公告）日：2020-07-07

  A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include assays for total bacterial growth, bacterial metabolic activity, and biofilm formation. The series of assays may be run once or more than once at each tier. A library of compounds is subject to tier A and only compounds meeting a primary parameter advance to tier B, and only tier B compounds meeting a confirmation parameter advance to tier C, and only tier C compounds meeting a dose-response parameter are identified as putative agents effective for inhibiting and/or eradicating a biofilm, further wherein the assays are conducted for each compound subject to the respective tier. The method is effective and validated for identifying agents which inhibit and/or kill Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms. Agents identified according to the high through-put screen and validated in follow-up experiments as effective for inhibiting and/or killing bacterial biofilms are also disclosed.

  本发明公开了一种高通量筛选方法，用于确定可有效抑制生物膜形成和/或杀死已形成的生物膜的制剂。该方法包括三个层级，每个层级包括三个特定的生物过程检测。层级为初筛、确认筛和剂量反应筛，生物过程测定包括细菌总生长、细菌代谢活性和生物膜形成测定。一系列检测可在每个层级进行一次或多次。将化合物库分为 A 层，只有符合主要参数的化合物才能进入 B 层，只有符合确认参数的 B 层化合物才能进入 C 层，只有符合剂量-反应参数的 C 层化合物才能被鉴定为对抑制和/或消除生物膜有效的假定制剂。该方法对于鉴定抑制和/或杀死表皮葡萄球菌、铜绿假单胞菌和鲍曼不动杆菌生物膜的制剂是有效的，也是经过验证的。还公开了根据高通量筛选确定并在后续实验中验证可有效抑制和/或杀死细菌生物膜的制剂。
• MULTI-TIERED, HIGH THROUGH-PUT SCREEN FOR COMPOUNDS EFFECTIVE AGAINST BACTERIAL BIOFILM COMPOUNDS EFFECTIVE FOR INHIBITING AND ERADICATING BACTERIAL BIOFILM
  申请人：UNIVERSITY OF CINCINNATI

  公开号：US20160024551A1

  公开（公告）日：2016-01-28

  A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include as says for total bacterial growth, bacterial metabolic activity, and biofilm formation.
• MULTI-TIERED HIGH THROUGH-PUT SCREEN FOR COMPOUNDS EFFECTIVE AGAINST BACTERIAL BIOFILM AND COMPOUNDS EFFECTIVE FOR INHIBITING AND ERADICATING BACTERIAL BIOFILM
  申请人：University of Cincinnati

  公开号：US20190127776A1

  公开（公告）日：2019-05-02

  A high through-put screening method for identifying agents effective for inhibiting biofilm formation and/or killing established biofilm are disclosed. The method includes three tiers, and each tier includes three specific biological process assays. The tier levels are a primary screen, a confirmation screen, and a dose-response screen, and the biological process assays include assays for total bacterial growth, bacterial metabolic activity, and biofilm formation. The series of assays may be run once or more than once at each tier. A library of compounds is subject to tier A and only compounds meeting a primary parameter advance to tier B, and only tier B compounds meeting a confirmation parameter advance to tier C, and only tier C compounds meeting a dose-response parameter are identified as putative agents effective for inhibiting and/or eradicating a biofilm, further wherein the assays are conducted for each compound subject to the respective tier. The method is effective and validated for identifying agents which inhibit and/or kill Staphylococcus epidermidis, Pseudomonas aeruginosa , and Acinetobacter baumannii biofilms. Agents identified according to the high through-put screen and validated in follow-up experiments as effective for inhibiting and/or killing bacterial biofilms are also disclosed.