difluoroborane {6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-yl}carboxylate | 215999-32-9

• 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: difluoroborane {6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-yl}carboxylate
• 英文别名: 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid-BF₂ chelate；6,7-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid BF₂ chelate；6,7-difluoro-1-[(1R,2S)-2-fluoro-1-cyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid difluoroboron complex；1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-6,7-difluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid difluoroborate ester；6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid difluoroboran complex；6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid difluoroboron complex；3-(((difluoroboryl)oxy)carbonyl)-6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-8-methoxyquinolin-4(1H)-one；difluoroboranyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylate
• CAS: 215999-32-9
• 化学式: C₁₄H₉BF₅NO₄
• 分子量: 361.033
• InChiKey: OGYDWXGJDJERBV-IONNQARKSA-N

物化性质

• 熔点：
  206-208 °C
• 沸点：
  434.8±55.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.65
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  difluoroborane {6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-yl}carboxylate 在 盐酸 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 21.08h， 生成 7-[3(S)-amino-1-pyrrolidinyl]-6-fluoro-1-[2(S)-fluoro-1(R)-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Studies on 8-Methoxyquinolones: Synthesis and Antibacterial Activity of 7-(3-Amino-4-substituted)pyrrolidinyl Derivatives.

  摘要：

  合成了一系列在C-7位带有3-氨基-4-甲基吡咯烷或3-氨基-4-氟甲基吡咯烷的8-甲氧基喹诺酮类化合物，并评估了它们的物理化学和生物学性质。所有合成的化合物对革兰氏阳性和阴性细菌的活性均比LVFX（3）更强。这些化合物的亲脂性增加对其单一静脉毒性和动物体内的药代动力学特性产生了理想的影响。在合成的化合物中，1-氟环丙基衍生物17和20，以及7-(顺-3-氨基-4-氟甲基吡咯烷基)衍生物19（DC-756h）在小鼠微核试验中显示阴性反应，而1-环丙基-7-(3-氨基吡咯烷基)衍生物16显示阳性反应。这些结果表明，将氟原子引入3-氨基吡咯烷基取代基和N-1环丙基取代基对遗传毒性产生了有利的影

  DOI：

  10.1248/cpb.48.1667
• 作为产物：
  描述：

  6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid 以92.7的产率得到difluoroborane {6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methoxy-4-oxoquinolin-3-yl}carboxylate
  参考文献：
  名称：

  Quinolonecarboxylic acid derivative

  摘要：

  (-)-7-[(7S)-7-氨基-5-氮杂螺[2.4]庚烷-5-基]-6-氟-1-[(1R,2S)-2-氟-1-环丙基]-1,4-二氢-8-甲氧基-4-氧代-3-喹啉羧酸.1HCl.1H2O及含有该化合物的抗菌组合物。本发明的化合物不仅表现出优异的抗菌活性和安全性，而且对光和湿度具有显著的稳定性，因此可用作抗菌剂。

  公开号：

  US06900225B2

文献信息

• Tri-, tetra-substituted-3-aminopyrrolidine derivative
  申请人：Takahashi Hisashi

  公开号：US20060264428A1

  公开（公告）日：2006-11-23

  A quinolone synthetic antibacterial agent and a therapeutic agent for an infection which exhibit broad spectrum and strong antibacterial activity for both Gram positive and Gram negative bacteria, and which are also highly safe are provided. The compound provided is represented by following formula (I): wherein R 1 and R 2 represent hydrogen atom, or the like; R 3 represents an alkyl group containing 1 to 6 carbon atoms, or the like; R 4 and R 5 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like, with the proviso that R 4 and R 5 do not simultaneously represent hydrogen atom; or the substituents R 4 and R 5 together represent (a) a 3- to 6-membered cyclic structure including the carbon atom shared by R 4 and R 5 to form a spirocyclic structure with the pyrrolidine ring; R 6 and R 7 independently represents hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, or the like; R 8 represents a halogen-substituted alkyl group containing 1 to 6 carbon atoms, or the like; X 1 represents hydrogen atom or a halogen atom; A represents nitrogen atom or a moiety represented by formula (II):

  提供了一种喹诺酮合成抗菌剂和治疗感染的药物，对革兰氏阳性和革兰氏阴性细菌均表现出广谱和强效的抗菌活性，并且具有很高的安全性。所提供的化合物由以下式（I）表示： 其中R1和R2代表氢原子，或类似物；R3代表含有1至6个碳原子的烷基基团，或类似物；R4和R5独立地代表氢原子，含有1至6个碳原子的烷基基团，或类似物，但R4和R5不同时代表氢原子；或取代基R4和R5一起代表（a）包括由R4和R5共享的碳原子形成螺环结构与吡咯烷环形成螺环结构的3至6成员环结构；R6和R7独立地代表氢原子，含有1至6个碳原子的烷基基团，或类似物；R8代表含有1至6个碳原子的卤代烷基基团，或类似物；X1代表氢原子或卤原子；A代表氮原子或由式（II）表示的基团。
• [EN] C-7 ISOXAZOLINYL QUINOLONE/NAPHTHYRIDINE DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS<br/>[FR] DÉRIVÉS DE C-7 ISOXAZOLINYL QUINOLONE/NAPHTHYRIDINE CONVENANT COMME AGENTS ANTI-BACTÉRIENS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010093341A1

  公开（公告）日：2010-08-19

  The present invention relates to C-7 isoxazolyl quinoline/naphthyridine derivatives useful as antimicrobial compounds, pharmaceutical compositions comprising said derivatives and the use of said derivatives and pharmaceutical compositions as antimicrobial agents against pathogenic microorganisms, particularly against resistant microbes.

  本发明涉及C-7异噁唑基喹啉/萘啶衍生物，可用作抗微生物化合物，包括含有这些衍生物的药物组合物以及将这些衍生物和药物组合物用作抗病原微生物的抗微生物剂，特别是对抗耐药菌。
• C-7 Isoxazolinyl Quinolone / Naphthyridine Derivatives Useful as Antibacterial Agents
  申请人：Macielag Mark J.

  公开号：US20090029980A1

  公开（公告）日：2009-01-29

  The present invention relates to C-7 isoxazolyl quinoline/naphthyridine derivatives useful as antimicrobial compounds, pharmaceutical compositions comprising said derivatives and the use of said derivatives and pharmaceutical compositions as antimicrobial agents against pathogenic microorganisms, particularly against resistant microbes.

  本发明涉及C-7异噁唑基喹啉/萘啶衍生物，可用作抗微生物化合物，包括含有该衍生物的药物组合物以及将该衍生物和药物组合物用作抗病原微生物的抗微生物剂，特别是对抗耐药微生物。
• Discovery of Novel 7-[(1&lt;i&gt;R&lt;/i&gt;,5&lt;i&gt;S&lt;/i&gt;)-1-Amino-5-fluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-1-[(1&lt;i&gt;R&lt;/i&gt;,2&lt;i&gt;S&lt;/i&gt;)-2-fluorocyclopropane]-8-(methoxy or methyl)quinolones
  作者：Satoshi Komoriya、Takashi Odagiri、Hiroaki Inagaki、Masatoshi Nagamochi、Rie Miyauchi、Ken-ichi Yoshida、Takahiro Kitamura、Hisashi Takahashi

  DOI：10.1248/cpb.c18-00671

  日期：2019.1.1

  A series of 8-methoxy or 8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole derivatives at the C-7 position was synthesized, and the pharmacological, physicochemical, and toxicological properties of the individual compounds were evaluated. Novel 8-methylquinolone 7, which includes a 3-amino-7-fluorooctahydrocyclopenta[c]pyrrole moiety at the C-7 position, showed potent antibacterial activity against both Gram-positive and negative pathogens. Compound 7 also demonstrated favorable pharmacokinetic and pharmacodynamic properties and an acceptably safe toxicological profile. Consequently, compound 7 was selected as a clinical candidate.

  合成了一系列在C-7位置上具有新型3-氨基辛氢环戊二氮杂呋喃衍生物的8-甲氧基或8-甲基喹啉类化合物，并评估了各个化合物的药理、物理化学和毒理特性。新型8-甲基喹啉类化合物7在C-7位置包含3-氨基-7-氟辛氢环戊二氮杂呋喃基团，显示出对革兰氏阳性和阴性病原体的强抗菌活性。化合物7还表现出良好的药代动力学和药效学特性，以及可接受的安全毒理特征。因此，化合物7被选为临床候选药物。
• WO2006/123792
  申请人：——

  公开号：——

  公开（公告）日：——