59197-90-9

Upstream product

• 574-92-5 4-hydroxy-7-(trifluoromethyl)-3-quinolinecarboxylic acid 

Relevant academic research and scientific papers

Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action

The related 3C and 3C-like proteinase (3Cpro and 3CLpro) of picornaviruses and coronaviruses, respectively, are good drug targets. As part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (SARS) 3CL proteinase against Hepatitis A virus (HAV) 3Cpro. Three of the compounds, which also had furan rings, inhibited the cleavage activity of HAV 3Cpro with Kics of 120-240 nM. HPLC-based assays revealed that the inhibitors were slowly hydrolyzed by both HAV 3Cpro and SARS 3CLpro, confirming the identity of the expected products. Mass spectrometric analyses indicated that this hydrolysis proceeded via an acyl-enzyme intermediate. Modeling studies indicated that the halopyridinyl moiety of the inhibitor fits tightly into the S1-binding pocket, consistent with the lack of tolerance of the inhibitors to modification in this portion of the molecule. These compounds are among the most potent non-peptidic inhibitors reported to date against a 3Cpro.

4-hydroxy-3-quinolinecarboxamides with antiarthritic and analgesic activities

A series of 4-hydroxy-3-quinolinecarboxamides has been synthesized and evaluated by the oral route as antiinflammatory agents in carrageenin-induced foot edema and adjuvant-induced arthritis and as analgesic agents in the acetic acid induced writhing test. Among the most active molecules, some have shown both analgesic and acute antiinflammatory activities. Others, such as compounds 24, 37, and 52, were only powerful peripherally acting analgesics. Compound 52, being active at 1 mg/kg (ED50), is the most potent compound in the series. Some analogues, substituted in the 2-position by an alcohol, ester, or amine function, displayed potent antiarthritic activity in the same range as that of piroxicam and were also active in acute tests of inflammation and nociception. They inhibited the activity of both cyclooxygenase and 5-lipoxygenase at micromolar concentrations. Compound 102 (RU 43526) showed potent antiarthritic activity (adjuvant-induced arthritis, ED50 = 0.7 mg/kg, po), and gastrointestinal tolerance (ED100 250 mg/kg, po) and thus it is presently undergoing an extensive pharmacological evaluation.

3-Quinoline-substituted 4-oxy-carboxamides

Novel 3-quinoline-carboxamides of the formula SPC1 Wherein R is selected from the group consisting of halogen, --CF3, --OCF3 and --SCF3 in the 7- or 8-position, R1 is selected from the group consisting of hydrogen and acyl of an aliphatic carboxylic acid of 2 to 4 carbon atoms, R3 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms and R2 is selected from the group consisting of thiazloyl, pyridinyl and oxazolyl and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and their preparation and novel intermediates.