887124-70-1

Upstream product

• 924-99-2 ethyl 3-(dimethylamino)acrylate 
• 35730-09-7 2,5-difluorobenzoyl chloride 
• 2991-28-8 2,5-difluorobenzoic acid 
• 1117-37-9 ethyl (E)-3-(dimethylamino)acrylate 

Downstream Products

• 1616491-42-9 6-(4-(3-(3-(benzyloxy)-2-(methoxycarbonyl)phenoxy)propyl)piperazin-1-yl)-1-cyclopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 931313-57-4 ethyl 1-benzyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 130436-10-1 1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 1338665-48-7 1-Benzyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 1616491-24-7 6-(4-benzylpiperazin-1-yl)-1-cyclopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 1616491-30-5 N-benzyl-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxamide 
• 1616491-33-8 N,1-dibenzyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxamide 
• 887124-71-2 ethyl 2-[(2,5-difluorophenyl)carbonyl]-3-(2,2-dimethylhydrazino)-2-propenoate 

Relevant academic research and scientific papers

4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B

Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC 50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

MACROLONE COMPOUNDS

A compound of formula (I) compositions comprising same, processes for their preparation and use of said compounds, particularly in the treatment of microbial infections.

MACROLONES - AMINO SUBSTITUTED QUINOLONES

Compounds of formula (I) or pharmaceutically acceptable derivatives thereof having antimicrobial activity are disclosed, as are processes for their preparation, compositions containing them and their use in medicine.