allyl 7-((4aS,7aS)-1-(tert-butoxycarbonyl)octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate | 1072452-97-1

• 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: allyl 7-((4aS,7aS)-1-(tert-butoxycarbonyl)octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate
• 英文别名: Allyl 7-((4aS,7aS)-1-(tert-butoxycarbonyl)-octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate；prop-2-enyl 7-[(4aS,7aS)-1-[(2-methylpropan-2-yl)oxycarbonyl]-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylate
• CAS: 1072452-97-1
• 化学式: C₂₉H₃₆FN₃O₆
• 分子量: 541.62
• InChiKey: JMLOVNBVPWLMJL-HTAPYJJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  allyl 7-((4aS,7aS)-1-(tert-butoxycarbonyl)octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 水 、 2-甲基苯亚磺酸钠 、 三乙胺 、 乙酰氯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.75h， 生成 7-((4aS,7aS)-1-(3,3-bis(diethylphosphono)propionyl)octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Phosphonated Fluoroquinolones, Antibacterial Analogs Thereof, and Methods for the Prevention and Treatment of Bone and Joint Infections

  摘要：

  本发明涉及磷酸化氟喹诺酮及其抗菌类似物，以及使用这些化合物的方法。这些化合物可用作抗生素，用于预防和/或治疗骨骼和关节感染，特别是用于预防和/或治疗骨髓炎。

  公开号：

  US20080287396A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 allyl 7-((4aS,7aS)-1-(tert-butoxycarbonyl)octahydropyrrolo[3,4-b]pyridin-6-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylate
  参考文献：
  名称：

  Phosphonated Fluoroquinolones, Antibacterial Analogs Thereof, and Methods for the Prevention and Treatment of Bone and Joint Infections

  摘要：

  本发明涉及磷酸化氟喹诺酮及其抗菌类似物，以及使用这些化合物的方法。这些化合物可用作抗生素，用于预防和/或治疗骨骼和关节感染，特别是用于预防和/或治疗骨髓炎。

  公开号：

  US20080287396A1

文献信息

• Siderophore‐Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells
  作者：James W. Southwell、Reyme Herman、Daniel J. Raines、Justin E. Clarke、Isabelle Böswald、Thorsten Dreher、Sophie M. Gutenthaler、Nicole Schubert、Jana Seefeldt、Nils Metzler‐Nolte、Gavin H. Thomas、Keith S. Wilson、Anne‐Kathrin Duhme‐Klair

  DOI：10.1002/chem.202202536

  日期：2023.2.7

  Siderophore-linked ruthenium catalysts were investigated for the activation of an antibacterial prodrug within cells. A fluoroquinolone prodrug was developed and shown to be compatible with the catalysts under micro-aerobic, biologically relevant conditions. The co-addition of the catalysts and prodrug to E. coli showed a combinative effect, with the dihydroxybenzoic acid- and azotochelin-linked catalysts showing

  联合攻击细菌：研究了铁载体连接的钌催化剂在细胞内激活抗菌前药的作用。开发了一种氟喹诺酮前药，并证明其在微需氧、生物学相关条件下与催化剂相容。将催化剂和前药共同添加到大肠杆菌中显示出组合效应，其中二羟基苯甲酸和偶氮螯合素连接的催化剂最有希望被细胞摄取，从而实现细胞内前药激活。
• Linking Bisphosphonates to the Free Amino Groups in Fluoroquinolones: Preparation of Osteotropic Prodrugs for the Prevention of Osteomyelitis
  作者：Tom J. Houghton、Kelly S. E. Tanaka、Ting Kang、Evelyne Dietrich、Yanick Lafontaine、Daniel Delorme、Sandra S. Ferreira、Frederic Viens、Francis F. Arhin、Ingrid Sarmiento、Dario Lehoux、Ibtihal Fadhil、Karine Laquerre、Jing Liu、Valérie Ostiguy、Hugo Poirier、Gregory Moeck、Thomas R. Parr、Adel Rafai Far

  DOI：10.1021/jm801007z

  日期：2008.11.13

  Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered antibiotics. Targeting antibiotics to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. By taking advantage, of the affinity of the bisphosphonate group for bone mineral, we have prepared a set of 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered to the free amino functionality on fluoroquinolone antibiotics. While all but one of the prodrugs were shown in vitro to be effective and rapid bone binders (over 90% in 1 h), only eight of them demonstrated the capacity to significantly regenerate the parent drug. In a rat model of the disease, a selected group of agents demonstrated their ability to prevent osteomyelitis when used in circumstances under which the parent drug had already been cleared and is thus inactive.