ethyl 2-chloro-4,5-difluoro-3-methylbenzoylacetate | 114152-86-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-chloro-4,5-difluoro-3-methylbenzoylacetate
• 英文别名: ethyl 2-chloro-3-methyl-4,5-difluorobenzoylacetate；ethyl 3-(2-chloro-4,5-difluoro-3-methylphenyl)-3-oxopropanoate
• CAS: 114152-86-2
• 化学式: C₁₂H₁₁ClF₂O₃
• 分子量: 276.667
• InChiKey: LWGPYPTWLDONNX-UHFFFAOYSA-N

物化性质

• 沸点：
  316.3±37.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-chloro-4,5-difluoro-3-methylbenzoylacetate 在 盐酸 、 乙酸酐 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(3-amino-4,6-difluorophenyl)-6,7-difluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group

  摘要：

  Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 C1 atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.

  DOI：

  10.1021/jm0205090
• 作为产物：
  描述：

  2-溴-4,5-二氟苯胺 在 盐酸 、 N-氯代丁二酰亚胺 、 硫酸 、 溴 、 sodium acetate 、 镍 、 三乙胺 、 copper(l) chloride 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 ethyl 2-chloro-4,5-difluoro-3-methylbenzoylacetate
  参考文献：
  名称：

  抗菌剂的研究。三，取代的1,4-二氢-8-甲基-4-氧代喹啉-3-羧酸的合成及抗菌活性。

  摘要：

  制备一系列在8位具有甲基的取代的4-氧代喹啉-3-羧酸，并测试其抗菌活性。7-（反式-3-氨基-4-甲基-1-吡咯烷基）-1-环丙基-1,4-二氢-6-氟-8-甲基-4-氧喹啉-3-羧酸（21）表现出强效对革兰氏阳性和革兰氏阴性细菌（包括铜绿假单胞菌）均具有抗菌活性。

  DOI：

  10.1248/cpb.38.2472

文献信息

• Quinolone derivatives and antibacterial agents containing the same
  申请人：Wakunaga Seiyaku Kabushiki Kaisha

  公开号：US05245037A1

  公开（公告）日：1993-09-14

  Antibacterial quinolone derivatives represented by the following formula [I] and salts thereof are disclosed. ##STR1## wherein R.sup.1 means a hydrogen atom or a carboxyl-protecting group; R.sup.2 denotes a hydrogen or halogen atom or a hydroxyl, lower alkoxyl, amino, aralkylamino, or mono- or di-(lower alkyl)amino group; A represents an oxygen or sulfur atom or N--R.sup.3 in which R.sup.3 is a hydrogen atom or an amino-protecting group; X is a hydrogen or halogen atom; Y means a nitrogen atom or C--R.sup.4 in which R.sup.4 is a hydrogen or halogen atom or a lower alkyl or lower alkoxyl group; and Z denotes a halogen atom or a substituted or unsubstituted heterocyclic group having at least one nitrogen atom as a hetero atom.

  公开了以下通式[I]表示的抗菌喹诺酮衍生物及其盐： ##STR1## 其中R1表示氢原子或羧基保护基；R2表示氢或卤素原子，或羟基、低级烷氧基、氨基、芳烷基氨基、或单-或二-(低级烷基)氨基；A表示氧或硫原子，或N--R3，其中R3是氢原子或氨基保护基；X是氢或卤素原子；Y表示氮原子或C--R4，其中R4是氢或卤素原子，或低级烷基或低级烷氧基；Z表示卤素原子，或至少有一个氮原子作为杂原子的取代或未取代的杂环基团。
• Benzoheterocyclic compounds
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US04874764A1

  公开（公告）日：1989-10-17

  Novel 4-oxoquinoline-3-carboxylic acid compounds of the formula: ##STR1## wherein R.sup.3 is C.sub.1 -C.sub.6 alkyl and R.sup.F is C.sub.1 -C.sub.6 alkyl, and a pharmaceutically acceptable salts thereof, said compounds having excellent antimicrobial activity and hence being useful as an antimicrobial agent, and a pharmaceutical composition containing said compound as an active ingredient.

  具有优异抗微生物活性的化合物为4-氧喹啉-3-羧酸类化合物，其化学式为：##STR1## 其中R.sup.3为C.sub.1 -C.sub.6烷基，R.sup.F为C.sub.1 -C.sub.6烷基，以及其药学上可接受的盐。这些化合物可用作抗微生物剂，并且包含该化合物作为活性成分的药物组合物。
• 1-Cyclopropyl-6-fl
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US04880806A1

  公开（公告）日：1989-11-14

  Novel 4-oxoquinoline-3-carboxylic acid compounds of the formula: ##STR1## wherein R.sup.2 is a heterocyclic group: ##STR2## in which R.sup.A is H, C.sub.1 -C.sub.6 alkyl or phenyl (C.sub.1 -C.sub.6) alkyl, R.sup.B is 2-oxo-1,3-dioxolenemethyl substituted by C.sub.1 -C.sub.6 alkyl, or C.sub.3 -C.sub.8 cycloalkyl, R.sup.C is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxycarbonyl, or phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.D is H or C.sub.1 -C.sub.6 alkyl, R.sup.G is C.sub.1 -C.sub.6 alkyl, and R.sup.H is C.sub.1 -C.sub.6 alkyl, phenyl(C.sub.1 -C.sub.6)alkyl, or C.sub.1 C.sub.6 alkanoyl, and R.sup.3 is C.sub.1 -C.sub.6 alkyl, or R.sup.3 is C.sub.1 -C.sub.6 alkyl having 1 to 3 substituents selected from OH, C.sub.1 -C.sub.6 alkoxy and halogen when R.sup.2 is ##STR3## or a salt thereof, said compounds having excellent antimicrobial activity and being useful as an antimicrobial agent, and a pharmaceutical composition containing said compound as an active ingredient.

  4-氧喹啉-3-羧酸衍生物的化学式：其中R.sup.2是一个杂环基团：在其中R.sup.A为H，C.sub.1 -C.sub.6烷基或苯基（C.sub.1 -C.sub.6）烷基，R.sup.B是2-氧代-1,3-二氧杂环戊烯甲基，被C.sub.1 -C.sub.6烷基或C.sub.3 -C.sub.8环烷基取代，R.sup.C是H，C.sub.1 -C.sub.6烷基，C.sub.1 -C.sub.6烷氧羰基，或苯基（C.sub.1 -C.sub.6）烷基，R.sup.D是H或C.sub.1 -C.sub.6烷基，R.sup.G是C.sub.1 -C.sub.6烷基，R.sup.H是C.sub.1 -C.sub.6烷基，苯基（C.sub.1 -C.sub.6）烷基，或C.sub.1 -C.sub.6酰基，R.sup.3是C.sub.1 -C.sub.6烷基，或R.sup.3是C.sub.1 -C.sub.6烷基，具有1至3个取代基，所选自OH，C.sub.1 -C.sub.6烷氧基和卤素，当R.sup.2是##STR3##或其盐，所述化合物具有出色的抗菌活性，可用作抗菌剂，并且含有所述化合物作为活性成分的药物组合物。
• 1-cyclopropyl-6-fluoro-8-alkyl-1,4-dihydro-4-oxo-quinoline-3-carboxylic
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US04855292A1

  公开（公告）日：1989-08-08

  Novel 4-oxoquinoline-3-carboxylic acid compounds of the formula: ##STR1## wherein R.sup.2 is 1-pyrrolidinyl which may have 1 to 2 substituents selected from the group consisting of (i) C.sub.1 -C.sub.6 alkyl, (ii) amino-(C.sub.1 -C.sub.6)alkyl, said amino being optionally substituted by 1 or 2 substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkanoyl, and C.sub.1 -C.sub.6 alkoxycarbonyl, (iii) amino which may be substituted by 1 or 2 substituents selected from C.sub.1 -C.sub.6 alkyl, phenyl(C.sub.1 -C.sub.6)alkyl, C.sub.1 -C.sub.6 alkoxycarbonyl, and C.sub.1 -C.sub.6 alkanoyl, and (iv) 2-oxo-1,3-dioxolenemethylamino which is substituted by C.sub.1 -C.sub.6 alkyl; or 1-piperidinyl which may have 1 to 3 substituents selected from oxo, hydroxy, halogen and C.sub.1 -C.sub.6 alkyl, and R.sup.3 is C.sub.1 -C.sub.6 alkyl, or a pharmaceutically acceptable salt thereof, said compounds having excellent antimicrobial activity and hence being useful as an antimicrobial agent, and a pharmaceutical composition containing said compound as an active ingredient.

  4-氧喹啉-3-羧酸化合物的结构式：其中R.sup.2为1-吡咯烷基，可以有1到2个取代基，所选自以下组合：(i) C.sub.1-C.sub.6烷基，(ii) 氨基-(C.sub.1-C.sub.6)烷基，该氨基可以选为1或2个取代基，所选自C.sub.1-C.sub.6烷基，C.sub.1-C.sub.6烷酰基和C.sub.1-C.sub.6氧代羰基，(iii) 氨基，可以被1或2个取代基所取代，所选自C.sub.1-C.sub.6烷基，苯基(C.sub.1-C.sub.6)烷基，C.sub.1-C.sub.6氧代羰基和C.sub.1-C.sub.6烷酰基，以及(iv) 2-氧代-1,3-二氧杂环戊烯基氨基，该氨基被C.sub.1-C.sub.6烷基取代；或1-哌啶基，可以有1到3个取代基，所选自氧代、羟基、卤素和C.sub.1-C.sub.6烷基，R.sup.3为C.sub.1-C.sub.6烷基，或其药学上可接受的盐，这些化合物具有出色的抗微生物活性，因此可用作抗微生物药物，并且含有该化合物作为活性成分的药物组合物。
• UEDA, HIRAKI;MIYAMOTA, HISASHI;AKI, SHINJI;OTSUKA, TATSUYA
  作者：UEDA, HIRAKI、MIYAMOTA, HISASHI、AKI, SHINJI、OTSUKA, TATSUYA

  DOI：——

  日期：——