179741-60-7

Upstream product

• 367-25-9 2,4-difluorophenylamine 
• 1583-58-0 2,4-difluoro-benzoic acid 
• 221560-09-4 2,4-Difluoro-5-nitrobenzoyl Chloride 
• 153775-33-8 2,4-difluoro-5-nitro-benzoic acid 
• 179741-61-8 tert-butyl (2,4-difluoro-5-nitrophenyl)carbamate 

Downstream Products

• 1315180-13-2 7-bromo-1-(5-tert-butoxycarbonylamino-2, 4-difluorophenyl)-2-ethyl-1, 4-dihydro-4-oxoquinoline 
• 1315179-93-1 7-bromo-1-(5-tert-butoxycarbonylamino-2, 4-difluorophenyl)-2-methyl-1, 4-dihydro-4-oxoquinoline 
• 179741-09-4 ethyl 1-(3-tert-butyloxycarbonylamino-4,6-difluorophenyl)-8-bromo-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate 
• 197520-73-3 ethyl 1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 535170-25-3 ethyl 1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-4-oxo-6,7,8-trifluoro-1,4-dihydroquinoline-3-carboxylate 
• 198013-94-4 ethyl 1-(5-tert-butoxycarbonylamino-2,4-difluorophenyl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate 

Relevant academic research and scientific papers

SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF

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.

A novel antibacterial 8-chloroquinolone with a distorted orientation of the N1-(5-amino-2,4-difluorophenyl) group

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 Cl 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.