(4S)-4-fluoro-1-methyl-L-proline | 1305324-16-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4S)-4-fluoro-1-methyl-L-proline
• 英文别名: (2S,4S)-4-fluoro-1-methylpyrrolidine-2-carboxylic acid
• CAS: 1305324-16-6
• 化学式: C₆H₁₀FNO₂
• 分子量: 147.149
• InChiKey: WWTABXAXNXQPOH-WHFBIAKZSA-N

物化性质

• 沸点：
  238.5±40.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

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 、 (4S)-4-fluoro-1-methyl-L-proline 在 sodium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 盐酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲醇 为溶剂， 生成 (2S,4S)-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]-4-fluoro-1-methylpyrrolidine-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

文献信息

• [EN] BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST<br/>[FR] COMPOSÉ INDOLE LIÉ AU BENZIMIDAZOLE AGISSANT COMME NOUVEL ANTAGONISTE D'IAP DIVALENT<br/>[ZH] 作为新型二价IAP拮抗剂的苯并咪唑联吲哚化合物
  申请人：MEDSHINE DISCOVERY INC

  公开号：WO2017186147A1

  公开（公告）日：2017-11-02

  本发明公开了一类作为IAP拮抗剂的新型二价苯并咪唑联吲哚化合物，具体公开了式(I)所示化合物或其药学上可接受的盐。
• Fluorocyclines. 2. Optimization of the C-9 Side-Chain for Antibacterial Activity and Oral Efficacy
  作者：Roger B. Clark、Diana K. Hunt、Minsheng He、Catherine Achorn、Chi-Li Chen、Yonghong Deng、Corey Fyfe、Trudy H. Grossman、Philip C. Hogan、William J. O’Brien、Louis Plamondon、Magnus Rönn、Joyce A. Sutcliffe、Zhijian Zhu、Xiao-Yi Xiao

  DOI：10.1021/jm201467r

  日期：2012.1.26

  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,