tert-butyl 5-amino-2,6-difluorophenylcarbamate | 179741-60-7

• 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: tert-butyl 5-amino-2,6-difluorophenylcarbamate
• 英文别名: tert-butyl (5-amino-2,4-difluorophenyl)carbamate；N-(t-butoxycarbonyl)-4,6-difluoro-m-phenylenediamine；N-(tert-butoxycarbonyl)-4,6-difluoro-m-phenylenediamine；tert-butyl N-(5-amino-2,4-difluorophenyl)carbamate
• CAS: 179741-60-7
• 化学式: C₁₁H₁₄F₂N₂O₂
• mdl: MFCD12432529
• 分子量: 244.241
• InChiKey: OWPOOOGXODOWIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-amino-2,6-difluorophenylcarbamate 在 盐酸 、 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：

  2,4-二氟苯甲酸 在 钯 sodium azide 、 草酰氯 、 硫酸 、 氢气 、 potassium nitrate 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.33h， 生成 tert-butyl 5-amino-2,6-difluorophenylcarbamate
  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

文献信息

• [EN] SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF<br/>[FR] COMPOSÉS DE PYRIMIDINE SUBSTITUÉE, COMPOSITIONS ET APPLICATIONS MÉDICINALES CORRESPONDANTES
  申请人：JUBILANT BIOSYS LTD

  公开号：WO2015025197A1

  公开（公告）日：2015-02-26

  The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.

  本公开涉及式(I)的嘧啶化合物，它们的立体异构体、互变异构体、药学上可接受的盐、多型体、溶剂合物和水合物。本公开还涉及制备这些嘧啶化合物的方法，以及含有它们的药物组合物。本公开的化合物在治疗、预防或抑制由表皮生长因子受体（EGFR）家族激酶介导的疾病和紊乱方面具有用途。
• Pyridonecarboxylic acid derivatives or salts thereof and antibacterial
  申请人：Wakunaga Seiyaku Kabushiki Kaisha

  公开号：US05910498A1

  公开（公告）日：1999-06-08

  The invention provides a pyridonecarboxylic acid derivative of the following general formula (1): ##STR1## wherein R.sup.1 is a hydrogen atom or carboxy protecting group, R.sup.2 is a nitro or substituted or unsubstituted amino group, R.sup.3 is a halogen atom, each of R.sup.4 and R.sup.5, which may be the same or different, is a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, A is a nitrogen atom or --CX.dbd. wherein X is a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, and Z is a halogen atom or a saturated cyclic amino group which may have a substituent, or a salt thereof and an antibacterial agent comprising the same.

  该发明提供了以下一般式（1）的吡啶酮羧酸衍生物： 其中R.sup.1是氢原子或羧基保护基，R.sup.2是硝基或取代或未取代的氨基，R.sup.3是卤素原子，R.sup.4和R.sup.5中的每一个，可以相同也可以不同，是氢原子、卤素原子、低烷基基团或低烷氧基团，A是氮原子或--CX.dbd.，其中X是氢原子、卤素原子、低烷基基团或低烷氧基团，Z是卤素原子或饱和环状氨基团，可能带有取代基，或其盐以及包含其的抗菌剂。
• HETEROCYCLIC COMPOUND HAVING AZOLE GROUP
  申请人：Oonishi Yuji

  公开号：US20130005760A1

  公开（公告）日：2013-01-03

  A heterocyclic compound of formula (I) or a salt thereof: wherein R 1 is an optionally protected amino group or an optionally substituted C 1-6 alkyl group; R 2 and R 3 are each independently a C 1-2 alkyl group; X is a hydrogen atom or a halogen atom; Z 1 is N or C—R 4 ; Z 2 is N or C—R 5 ; Z 3 is N or C—R 6 ; Z 4 is N or C—R 7 ; R 4 , R 5 , R 6 , and R 7 are each independently a hydrogen atom, a halogen atom, an optionally protected amino group, or a C 1-6 alkylsulfonyl group; Z is CH or N; and A is a methylene group or a bond, which has an excellent anti-HIV activity and is useful as an anti-HIV agent.

  化合物(I)的异环化合物或其盐：其中，R1是可选地保护的氨基或可选地取代的C1-6烷基；R2和R3各自独立地是C1-2烷基；X是氢原子或卤素原子；Z1是N或C-R4；Z2是N或C-R5；Z3是N或C-R6；Z4是N或C-R7；R4、R5、R6和R7各自独立地是氢原子、卤素原子、可选地保护的氨基或C1-6烷基磺酰基；Z是CH或N；A是亚甲基或键，具有出色的抗HIV活性，可用作抗HIV剂。
• SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
  申请人：JUBILANT BIOSYS LIMITED

  公开号：US20160207905A1

  公开（公告）日：2016-07-21

  The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.

  本公开涉及式（I）的嘧啶化合物，它们的立体异构体，互变异构体，药学上可接受的盐，多晶形，溶剂化物和水合物。本公开还涉及制备这些嘧啶化合物的过程，以及含有它们的制药组合物。本公开所述化合物在治疗，预防或抑制由表皮生长因子受体（EGFR）家族激酶介导的疾病和疾病方面具有用处。
• NOVEL PYRIDONECARBOXYLATE DERIVATIVE OR SALT THEREOF AND ANTIBACTERIAL CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：WAKUNAGA SEIYAKU KABUSHIKI KAISHA

  公开号：EP0787720A1

  公开（公告）日：1997-08-06

  The invention provides a pyridonecarboxylic acid derivative of the following general formula (1): wherein R1 is a hydrogen atom or carboxy protecting group, R2 is a nitro or substituted or unsubstituted amino group, R3 is a halogen atom, each of R4 and R5, which may be the same or different, is a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, A is a nitrogen atom or - CX= wherein X is a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, and Z is a halogen atom or a saturated cyclic amino group which may have a substituent, or a salt thereof and an antibacterial agent comprising the same.

  本发明提供了以下通式(1)的吡啶甲酸衍生物： 其中 R1 是氢原子或羧基保护基团，R2 是硝基或取代或未取代的氨基，R3 是卤素原子，R4 和 R5（可以相同或不同）各自是氢原子、卤素原子、低级烷基或低级烷氧基，A 是氮原子或 - CX= 其中 X 是氢原子、卤素原子、低级烷基或低级烷氧基，Z 是卤素原子或饱和环状氨基（可以有取代基），或其盐以及由其组成的抗菌剂。