S-(1,1-bis(diethylphosphono)methylcarbamoyl)methyl 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-carbothioate | 925684-85-1

• 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: S-(1,1-bis(diethylphosphono)methylcarbamoyl)methyl 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-carbothioate
• 英文别名: tert-butyl (4aS,7aS)-6-[3-[2-[bis(diethoxyphosphoryl)methylamino]-2-oxoethyl]sulfanylcarbonyl-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinolin-7-yl]-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b]pyridine-1-carboxylate
• CAS: 925684-85-1
• 化学式: C₃₇H₅₅FN₄O₁₂P₂S
• 分子量: 860.875
• InChiKey: SYMXWHSPNAHZAW-NEKDWFFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  57
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  205
• 氢给体数：
  1
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  S-(1,1-bis(diethylphosphono)methylcarbamoyl)methyl 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-carbothioate 在 三甲基溴硅烷 、 sodium hydroxide 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 41.0h， 以25%的产率得到S-(1,1-bisphosphonomethylcarbamoyl)methyl 1-cyclopropyl-6-fluoro-1,4-dihydro-7-((4aS,7aS)-octahydropyrrolo[3,4-b]pyridin-6-yl)-8-methoxy-4-oxoquinoline-3-carbothioate
  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 、 2-氟-1-甲基吡啶翁对甲苯磺酸盐 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 S-(1,1-bis(diethylphosphono)methylcarbamoyl)methyl 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-carbothioate
  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

• Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis
  作者：Kelly S.E. Tanaka、Tom J. Houghton、Ting Kang、Evelyne Dietrich、Daniel Delorme、Sandra S. Ferreira、Laurence Caron、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：10.1016/j.bmc.2008.09.010

  日期：2008.10

  Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering antibacterial agents to the bone may overcome the difficulties in treating this illness by effectively concentrating the antibiotic at the site of infection and by limiting the toxicity that may result from systemic exposure to the large doses conventionally used. Using bisphosphonates as osteophilic functional groups, different forms of fluoroquinolone esters were synthesized and evaluated for their ability to bind bone and to release the parent antibacterial agent. Bisphosphonated glycolamide fluoroquinolone esters were found to present a profile consistent with effective and rapid bone binding and efficient release of the active drug moiety. They were assessed for their ability to prevent bone infection in vivo and were found to be effective when the free fluoroquinolones were not (C) 2008 Elsevier Ltd. All rights reserved.