ethyl 1-{(3S)-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate | 181941-65-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 1-{(3S)-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate
• 英文别名: (4S)-4-(1-ethoxycarbonylcyclopropyl)-1-[(S)-1-phenylethyl]-2-pyrrolidinethione；ethyl 1-[(3S)-1-[(1S)-1-phenylethyl]-5-sulfanylidenepyrrolidin-3-yl]cyclopropane-1-carboxylate
• CAS: 181941-65-1
• 化学式: C₁₈H₂₃NO₂S
• 分子量: 317.452
• InChiKey: YPZZOUYSTMALSC-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-{(3S)-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate 在 Raney Ni W-6 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以91%的产率得到ethyl 1-{(3S)-1-[(S)-1-phenylethyl]pyrrolidin-3-yl}cyclopropanecarboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3R)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents

  摘要：

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.

  DOI：

  10.1021/jm020328y
• 作为产物：
  描述：

  ethyl 3-(1-ethoxycarbonylcyclopropan-1-yl)-3-hydroxybutanoate 在 platinum(IV) oxide 劳森试剂 、 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 偶氮二异丁腈 、 氢气 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 51.0h， 生成 ethyl 1-{(3S)-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3R)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents

  摘要：

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.

  DOI：

  10.1021/jm020328y
• 作为试剂：
  描述：

  4-(1-ethoxycarbonylcyclopropyl)-1-[(S)-1-phenylethyl]-2-pyrrolidone 、 劳森试剂 、 乙酸乙酯 、 苯 在 正己烷 、 ethyl 1-{(3S)-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate 作用下， 反应 1.0h， 以isopropyl ether=1:1, 6.81 g (as 62% (4S) content) of the title compound was obtained as needle crystals的产率得到异丙醚
  参考文献：
  名称：

  Pyridonecarboxylic acid derivatives substituted by a bicyclic amino

  摘要：

  本发明涉及一种由以下式（I）表示的N.sub.1-(卤代环丙基)-取代吡啶酮羧酸衍生物：##STR1## 其中X.sup.1是卤素原子或氢原子；X.sup.2是卤素原子；R.sup.1是氢原子、羟基、硫醇基、卤代甲基基团、氨基、烷基或可能具有取代基的烷氧基；R.sup.2是由以下式（II）表示的基团：##STR2## 其中R.sup.3和R.sup.4独立地是氢原子或烷基，n是1或2的整数；A是氮原子或以下式（III）的部分结构：##STR3## 其中X.sup.3是氢原子、卤素原子、氰基、氨基、烷基、卤代甲基基团、烷氧基或卤代甲氧基基团，可能具有取代基；而R是氢原子、苯基、乙酰氧甲基基团、季戊酰氧甲基基团、乙氧羰基基团、胆碱基团、二甲氨基乙基基团、5-吲哚基基团、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、烷氧基甲基基团或苯基烷基基团，并提供一种作为抗菌药物有用的杂环化合物。

  公开号：

  US05849757A1

文献信息

• HETEROCYCLIC COMPOUNDS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0807630A1

  公开（公告）日：1997-11-19

  This invention relates to a N1-(halogenocyclopropyl)-substituted pyridonecarboxylic acid derivative represented by the following formula (I): wherein X1 is a halogen atom or a hydrogen atom; X2 is a halogen atom; R1 is a hydrogen atom, a hydroxyl group, a thiol group, a halogenomethyl group, an amino group, an alkyl group or an alkoxy group which may have a substituent group; R2 is a group represented by the following formula (II): wherein R3 and R4 are independently a hydrogen atom or an alkyl group and n is an integer of 1 or 2; A is a nitrogen atom or a partial structure of the following formula (III): wherein X3 is a hydrogen atom, a halogen atom, a cyano group, an amino group, an alkyl group, a halogenomethyl group, an alkoxyl group or a halogenomethoxyl group which may have a substituent group; and R is 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 phthalidynyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, a 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxymethyl group or a phenylalkyl group, and provides a heterocyclic compound useful as antibacterial drugs.

  本发明涉及由下式(I)代表的N1-(卤代环丙基)-取代的吡啶羧酸衍生物： 其中 X1 是卤素原子或氢原子；X2 是卤素原子；R1 是氢原子、羟基、硫醇基、卤代甲基、氨基、烷基或烷氧基，其中烷基或烷氧基可带有取代基；R2 是由下式（II）代表的基团： 其中 R3 和 R4 独立地为氢原子或烷基，n 为 1 或 2 的整数； A 为氮原子或下式（III）的部分结构： 其中 X3 是氢原子、卤素原子、氰基、氨基、烷基、卤代甲基、烷氧基或可带有取代基的卤代甲氧基；和 R 是氢原子、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-茚基基、酞酰基、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，并提供一种可用作抗菌药物的杂环化合物。
• Pyridonecarboxylic acid derivatives and their use as antibacterial agents
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1304329B1

  公开（公告）日：2008-10-15
• US5849757A
  申请人：——

  公开号：US5849757A

  公开（公告）日：1998-12-15
• Pyridonecarboxylic acid derivatives substituted by a bicyclic amino
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05849757A1

  公开（公告）日：1998-12-15

  This invention relates to a N.sub.1 -(halogenocyclopropyl)-substituted pyridonecarboxylic acid derivative represented by the following formula (I): ##STR1## wherein X.sup.1 is a halogen atom or a hydrogen atom; X.sup.2 is a halogen atom; R.sup.1 is a hydrogen atom, a hydroxyl group, a thiol group, a halogenomethyl group, an amino group, an alkyl group or an alkoxy group which may have a substituent group; R.sup.2 is a group represented by the following formula (II): ##STR2## wherein R.sup.3 and R.sup.4 are independently a hydrogen atom or an alkyl group and n is an integer of 1 or 2; A is a nitrogen atom or a partial structure of the following formula (III): ##STR3## wherein X.sup.3 is a hydrogen atom, a halogen atom, a cyano group, an amino group, an alkyl group, a halogenomethyl group, an alkoxyl group or a halogenomethoxyl group which may have a substituent group; and R is 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 phthalidynyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl group, a 3-acetoxy-2-oxobutyl group, an alkyl group, an alkoxymethyl group or a phenylalkyl group, and provides a heterocyclic compound useful as antibacterial drugs.

  这项发明涉及一种由以下式（I）表示的N.sub.1-(卤代环丙基)-取代吡啶酮羧酸衍生物：其中X.sup.1是卤素原子或氢原子；X.sup.2是卤素原子；R.sup.1是氢原子、羟基、硫醇基、卤代甲基基团、氨基、烷基或可能具有取代基团的烷氧基；R.sup.2是由以下式（II）表示的基团：其中R.sup.3和R.sup.4独立地是氢原子或烷基，n是1或2的整数；A是氮原子或以下式（III）的部分结构：其中X.sup.3是氢原子、卤素原子、氰基、氨基、烷基、卤代甲基基团、烷氧基或可能具有取代基团的卤代甲氧基；R是氢原子、苯基、乙酰氧甲基基团、戊酰氧甲基基团、乙氧羰基、胆碱基团、二甲氨基乙基基团、5-茚基团、邻苯二酰基团、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、烷氧甲基或苯基烷基基团，并提供一种用作抗菌药物的杂环化合物。
• Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1<i>R</i>,2<i>S</i>)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3<i>R</i>)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents
  作者：Hiroaki Inagaki、Satoru Miyauchi、Rie N. Miyauchi、Haruko C. Kawato、Hitoshi Ohki、Norikazu Matsuhashi、Katsuhiro Kawakami、Hisashi Takahashi、Makoto Takemura

  DOI：10.1021/jm020328y

  日期：2003.3.1

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.