(4S,4aS,5aR,12aS)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide | 1207283-60-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: (4S,4aS,5aR,12aS)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
• CAS: 1207283-60-0
• 化学式: C₂₁H₂₂FN₃O₇
• 分子量: 447.42
• InChiKey: SQYLTQVZEBFMMP-AYYJOUFOSA-N

物化性质

• 沸点：
  804.7±65.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.16
• 重原子数：
  32.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  187.41
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (4S,4aS,5aR,12aS)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 (2S)-N-[(5aR,6aS,7S,10aS)-9-carbamoyl-7-(dimethylamino)-4-fluoro-1,8,10a,11-tetrahydroxy-10,12-dioxo-5,5a,6,6a,7,10,10a,12-octahydrotetracen-2-yl]-1-methylpiperidine-2-carboxamide dihydrochloride
  参考文献：
  名称：

  Fluorocyclines. 2. Optimization of the C-9 Side-Chain for Antibacterial Activity and Oral Efficacy

  摘要：

  Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents,

  DOI：

  10.1021/jm201467r
• 作为产物：
  描述：

  (1R,3S,4S,11S)-8-(benzyloxy)-11-[(tert-butyldimethylsilyl)oxy]-4-(dimethylamino)-19-fluoro-12-hydroxy-10,14-dioxo-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-hexaen-16-yl tert-butyl carbonate 在 硫酸 、 palladium 10% on activated carbon 、 氢氟酸 、 氢气 、 硝酸 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 21.5h， 生成 (4S,4aS,5aR,12aS)-9-amino-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
  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。
• 一种四环素衍生物及其用途
  申请人：四川科伦博泰生物医药股份有限公司

  公开号：CN107759503A

  公开（公告）日：2018-03-06

  本发明涉及一种四环素衍生物，其制备方法及其用途。具体地，本发明涉及一种通式(Ⅰ)的化合物，或其异构体、盐、酯、溶剂化物或水合物、化学保护的形式和前药代谢产物、晶型。并且，本发明还涉及该化合物的制备方法及用途。
• C7-fluoro substituted tetracycline compounds
  申请人：Tetraphase Pharmaceuticals, Inc.

  公开号：EP2682387A2

  公开（公告）日：2014-01-08

  The present invention is directed to a compound falling under 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.

  本发明涉及一种属于结构式（A）的化合物： 或其药学上可接受的盐。结构式（A）的变量在此定义。还描述了一种包含结构式（A）化合物的药物组合物及其治疗用途。
• C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS
  申请人：Tetraphase Pharmaceuticals, Inc.

  公开号：EP2323972B1

  公开（公告）日：2013-07-03
• 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.