(1R,3S,4S,11S)-8-(benzyloxy)-4-(dimethylamino)-19-fluoro-11,12,16-trihydroxy-6-oxa-7-azapentacyclo-[11.8.0.0.(3,11)0.(5,9)0(15,20)]henicosa-5(9),7,12,15(20),16,18-hexaene-10,14-dione | 1207283-58-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (1R,3S,4S,11S)-8-(benzyloxy)-4-(dimethylamino)-19-fluoro-11,12,16-trihydroxy-6-oxa-7-azapentacyclo-[11.8.0.0.(3,11)0.(5,9)0(15,20)]henicosa-5(9),7,12,15(20),16,18-hexaene-10,14-dione
• CAS: 1207283-58-6
• 化学式: C₂₈H₂₅FN₂O₇
• 分子量: 520.514
• InChiKey: TXTSCGPBRJSGEC-XLDMGRSHSA-N

物化性质

• 沸点：
  787.7±60.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  38.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  133.33
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (1R,3S,4S,11S)-8-(benzyloxy)-4-(dimethylamino)-19-fluoro-11,12,16-trihydroxy-6-oxa-7-azapentacyclo-[11.8.0.0.(3,11)0.(5,9)0(15,20)]henicosa-5(9),7,12,15(20),16,18-hexaene-10,14-dione 在 N,N-二甲基丙烯基脲 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 5.67h， 生成 (4S,4aS,5aR,12aS)-9-[2-(azetidin-1-yl)acetamido]-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide dihydrochloride
  参考文献：
  名称：

  Fluorocyclines. 1. 7-Fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: A Potent, Broad Spectrum Antibacterial Agent

  摘要：

  This and the accompanying report (DOI: 10.1021/jm201467r) describe the design, synthesis, and evaluation of a new generation of tetracycline antibacterial agents, 7-fluoro-9-substituted-6-demethyl-6-deoxytetracyclines ("fluorocyclines"), accessible through a recently developed total synthesis approach. These fluorocyclines possess potent antibacterial activities against multidrug resistant (MDR) Gram-positive and Gram-negative pathogens. One of the fluorocyclines, 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline (17j, also known as TP-434, 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference, Boston, MA, September 12-15, 2010, poster F1-2157), is currently undergoing phase 2 clinical trials in patients with complicated intra-abdominal infections (cIAI).

  DOI：

  10.1021/jm201465w
• 作为产物：
  描述：

  phenyl 3-fluoro-6-methoxy-2-methylbenzoate 在 4-二甲氨基吡啶 、 四甲基乙二胺 、 氢氟酸 、 三溴化硼 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 22.08h， 生成 (1R,3S,4S,11S)-8-(benzyloxy)-4-(dimethylamino)-19-fluoro-11,12,16-trihydroxy-6-oxa-7-azapentacyclo-[11.8.0.0.(3,11)0.(5,9)0(15,20)]henicosa-5(9),7,12,15(20),16,18-hexaene-10,14-dione
  参考文献：
  名称：

  Fluorocyclines. 1. 7-Fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: A Potent, Broad Spectrum Antibacterial Agent

  摘要：

  This and the accompanying report (DOI: 10.1021/jm201467r) describe the design, synthesis, and evaluation of a new generation of tetracycline antibacterial agents, 7-fluoro-9-substituted-6-demethyl-6-deoxytetracyclines ("fluorocyclines"), accessible through a recently developed total synthesis approach. These fluorocyclines possess potent antibacterial activities against multidrug resistant (MDR) Gram-positive and Gram-negative pathogens. One of the fluorocyclines, 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline (17j, also known as TP-434, 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference, Boston, MA, September 12-15, 2010, poster F1-2157), is currently undergoing phase 2 clinical trials in patients with complicated intra-abdominal infections (cIAI).

  DOI：

  10.1021/jm201465w

文献信息

• [EN] C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS<br/>[FR] COMPOSÉS DE TÉTRACYCLINE C7-FLUOROSUBSTITUÉE
  申请人：TETRAPHASE PHARMACEUTICALS INC

  公开号：WO2010017470A1

  公开（公告）日：2010-02-11

  The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

  本发明涉及一种由结构式（A）表示的化合物，或其药学上可接受的盐。结构式（A）的变量在此处定义。还描述了包括结构式（A）化合物的药物组合物及其治疗用途。
• J. Med. Chem. 2012, 55, 597-605
  作者：

  DOI：——

  日期：——
• C7-fluoro substituted tetracycline compounds
  申请人：Zhou Jingye

  公开号：US20100105671A1

  公开（公告）日：2010-04-29

  The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.
• C7-Fluoro Substituted Tetracycline Compounds
  申请人：Zhou Jingye

  公开号：US20120302527A1

  公开（公告）日：2012-11-29

  The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.
• C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS
  申请人：Tetraphase Pharmaceuticals, Inc.

  公开号：US20150274643A1

  公开（公告）日：2015-10-01

  The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.