2-[(4aS,11aR,12aS,13S)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-10-fluoro-4,4a,6,11,11a,12,12a,13-octahydro-5-hydroxy-4,6-dioxo-3,7-bis(phenylmethoxy)isoxazolo[5',4':6,7]naphth[2,3-g]isoquinolin-8-yl]-imidodicarbonic acid, 1,3-bis(1,1-dimethylethyl) ester | 1254367-88-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-[(4aS,11aR,12aS,13S)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-10-fluoro-4,4a,6,11,11a,12,12a,13-octahydro-5-hydroxy-4,6-dioxo-3,7-bis(phenylmethoxy)isoxazolo[5',4':6,7]naphth[2,3-g]isoquinolin-8-yl]-imidodicarbonic acid, 1,3-bis(1,1-dimethylethyl) ester
• CAS: 1254367-88-8
• 化学式: C₅₀H₆₁FN₄O₁₁Si
• 分子量: 941.138
• InChiKey: ADLBLQWIPXOGDA-FWCYENFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.49
• 重原子数：
  67.0
• 可旋转键数：
  10.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  180.06
• 氢给体数：
  1.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  2-[(4aS,11aR,12aS,13S)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-10-fluoro-4,4a,6,11,11a,12,12a,13-octahydro-5-hydroxy-4,6-dioxo-3,7-bis(phenylmethoxy)isoxazolo[5',4':6,7]naphth[2,3-g]isoquinolin-8-yl]-imidodicarbonic acid, 1,3-bis(1,1-dimethylethyl) ester 在 盐酸 、 palladium 10% on activated carbon 、 氢氟酸 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 反应 20.0h， 生成 9-amino-6-demethyl-6-deoxy-7-fluoro-8-azatetracycline
  参考文献：
  名称：

  8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents

  摘要：

  A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection.

  DOI：

  10.1021/jm1015389
• 作为产物：
  描述：

  phenyl 3-(benzyloxy)-2,6-dibromo-5-methylisonicotinate 在 吡啶 、 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 四甲基乙二胺 、 氨基甲酸叔丁酯 、 氢氟酸 、 caesium carbonate 、 二异丙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.58h， 生成 2-[(4aS,11aR,12aS,13S)-13-(dimethylamino)-4a-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-10-fluoro-4,4a,6,11,11a,12,12a,13-octahydro-5-hydroxy-4,6-dioxo-3,7-bis(phenylmethoxy)isoxazolo[5',4':6,7]naphth[2,3-g]isoquinolin-8-yl]-imidodicarbonic acid, 1,3-bis(1,1-dimethylethyl) ester
  参考文献：
  名称：

  8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents

  摘要：

  A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection.

  DOI：

  10.1021/jm1015389

文献信息

• [EN] 8-AZA TETRACYCLINE COMPOUNDS<br/>[FR] COMPOSÉS DE 8-AZA TÉTRACYCLINE
  申请人：TETRAPHASE PHARMACEUTICALS INC

  公开号：WO2010129055A1

  公开（公告）日：2010-11-11

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

  本发明涉及一种由结构式（I）表示的化合物或其药用盐。结构式I的变量在此定义。还描述了包括结构式I化合物的药物组合物及其治疗用途。