7-[3(S)-amino-4(S)-fluoromethyl-1-pyrrolidinyl]-6-fluoro-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid | 218281-25-5

• 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: 7-[3(S)-amino-4(S)-fluoromethyl-1-pyrrolidinyl]-6-fluoro-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid
• 英文别名: DC-756h；H6RY8HR9LM；7-[(3S,4S)-3-amino-4-(fluoromethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid
• CAS: 218281-25-5
• 化学式: C₁₉H₂₁F₂N₃O₄
• 分子量: 393.39
• InChiKey: XGZPDXTUAWRGLD-LKFCYVNXSA-N

物化性质

• 沸点：
  618.0±55.0 °C(Predicted)
• 密度：
  1.451±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3(S)-tert-butoxycarbonylamino-4(S)-fluoromethyl-1-[N-1(R)-phenylethyl]-2-pyrrolidone 在 palladium on activated charcoal 盐酸 、 硼烷四氢呋喃络合物 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 56.08h， 生成 7-[3(S)-amino-4(S)-fluoromethyl-1-pyrrolidinyl]-6-fluoro-1-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

文献信息

• CIS-SUBSTITUTED FLUOROMETHYLPYRROLIDINE DERIVATIVE
  申请人：——

  公开号：US20020072608A1

  公开（公告）日：2002-06-13

  An antibacterial drug having potent antibacterial activities upon various bacteria including resistant strains and high safety is disclosed, which comprises as an active ingredient, quinolone derivatives represented by the following formula (I), its salts or hydrates thereof: 1 wherein R 1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R 2 represents a halogenomethoxyl group or an alkoxyl group, R 3 represents an alkyl group, an alkenyl group, a halogenoalkyl group, a cyclic alkyl group, a heteroaryl group, an alkoxyl group or an alkylamino group, and R 4 represents a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidinyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxylmethyl group or a phenylalkyl group. These substituents may further have additional substituents.

  揭示了一种具有对各种细菌具有强效抗菌活性，包括耐药菌株和高安全性的抗菌药物，其包括以下式(I)所代表的喹诺酮衍生物作为活性成分，其盐或水合物：其中R1代表氢原子或具有1至6个碳原子的烷基基团，R2代表卤代甲氧基基团或烷氧基基团，R3代表烷基基团、烯基基团、卤代烷基基团、环烷基基团、杂环芳基团、烷氧基基团或烷基氨基基团，R4代表氢原子、苯基、乙酰氧甲基基团、戊二酰氧甲基基团、乙氧羰基基团、胆碱基团、二甲氨基乙基基团、5-茚基基团、邻苯二甲酰基基团、5-烷基-2-氧代-1,3-二氧杂环戊-4-基甲基基团、3-乙酰氧基-2-氧代丁基基团、烷基基团、烷氧基甲基基团或苯基烷基基团。这些取代基还可能具有额外的取代基。
• Cis-substituted fluoromethylpyrrolidine derivative
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06656952B2

  公开（公告）日：2003-12-02

  An antibacterial drug having potent antibacterial activities upon various bacteria including resistant strains and high safety is disclosed, which comprises as an active ingredient, quinolone derivatives represented by the following formula (I), its salts or hydrates thereof: wherein R1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R2 represents a halogenomethoxyl group or an alkoxyl group, R3 represents an alkyl group, an alkenyl group, a halogenoalkyl group, a cyclic alkyl group, a heteroaryl group, an alkoxyl group or an alkylamino group, and R4 represents a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidinyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxylmethyl group or a phenylalkyl group. These substituents may further have additional substituents.

  本发明公开了一种具有强大的抗菌活性，对包括耐药菌株在内的各种细菌具有高安全性的抗菌药物，其包括以下式（I）所表示的喹诺酮衍生物作为活性成分，其盐或水合物：其中R1表示氢原子或具有1至6个碳原子的烷基；R2表示卤代甲氧基基团或烷氧基基团；R3表示烷基、烯基、卤代烷基、环烷基、杂环芳基、烷氧基或烷基氨基基团；R4表示氢原子、苯基、乙酰氧甲基、季戊酰氧甲基、乙氧羰基、胆碱基、二甲基氨基乙基基团、5-吲哚基基团、邻苯二甲酰亚胺基团、5-烷基-2-氧代-1,3-二氧杂环-4-基甲基基团、3-乙酰氧基-2-氧代丁基基团、烷基、烷氧基甲基基团或苯基烷基基团。这些取代基可能进一步具有其他取代基。
• CIS-SUBSTITUTED FLUOROMETHYLPYRROLIDINE DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0995744A1

  公开（公告）日：2000-04-26

  An antibacterial drug having potent antibacterial activities upon various bacteria including resistant strains and high safety is disclosed, which comprises as an active ingredient, quinolone derivatives represented by the following formula (I), its salts or hydrates thereof: wherein R1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R2 represents a halogenomethoxyl group or an alkoxyl group, R3 represents an alkyl group, an alkenyl group, a halogenoalkyl group, a cyclic alkyl group, a heteroaryl group, an alkoxyl group or an alkylamino group, and R4 represents a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidinyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxylmethyl group or a phenylalkyl group. These substituents may further have additional substituents.

  本发明公开了一种对包括耐药菌株在内的各种细菌具有强效抗菌活性且安全性高的抗菌药，其活性成分包括下式(I)代表的喹诺酮衍生物、其盐类或水合物： 其中 R1 代表氢原子或具有 1 至 6 个碳原子的烷基、 R2 代表卤代甲氧基或烷氧基、 R3 代表烷基、烯基、卤代烷基、环烷基、杂芳基、烷氧基或烷基氨基，以及 R4 代表氢原子、苯基、乙酰氧甲基、新戊酰氧甲基、乙氧基羰基、胆碱基、二甲基氨基乙基、5-茚满基、酞丁基、5-烷基-2-氧代-1,3-二氧戊环-4-基甲基、3-乙酰氧基-2-氧代丁基、烷基、烷氧基甲基或苯基烷基。这些取代基可进一步具有其他取代基。
• Pyridobenzoxazine derivative
  申请人：Takemura Makoto

  公开号：US20070191356A1

  公开（公告）日：2007-08-16

  A quinolone antimicrobial agent having potent antimicrobial activity against gram positive and gram negative bacteria and having high safety is provided. A compound represented by the following formula (1): [Chemical formula 1] [wherein, R 1 : hydrogen, alkyl, cycloalkyl, or substituted carbonyl derived from amino acid, peptide or tripeptide; R 2 : hydrogen, alkyl, or cycloalkyl; R 3 : hydrogen, amino, halogen, or alkyl; R 4 : hydrogen, phenyl, acetoxymethyl, pivaloyloxymethyl, ethoxycarbonyl, choline, dimethylaminoethyl, 5-indanyl, phthalidinyl, 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl, 3-acetoxy-2-oxobutyl, alkyl, alkoxymethyl, or phenylalkyl; X, X 1 , X 2 : hydrogen or halogen] or salt thereof, or a hydrate thereof; and antimicrobial agent and therapeutic agent for infections, each containing the compound, salt thereof or a hydrate thereof.
• US6656952B2
  申请人：——

  公开号：US6656952B2

  公开（公告）日：2003-12-02