Abstract
A new series of polysubstituted 1-aryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and pyrazolo[3,4-b]pyridine-5-carbonitriles and pyrido[2,3-d]pyrimidine-6-carbonitriles have been synthesized and tested for their antifibrotic activity. Among the tested compounds, compounds IIc and IVb exhibited higher antifibrotic activity than the standard pirfenidone PD with a reduction of the hydroxyproline level to 50 and 140 micromol/lung, respectively. However, bicyclic pyridone VIIIb displayed a high mortality rate. Detailed syntheses, spectroscopic and biological data are reported.
MeSH terms
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Administration, Oral
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Alanine Transaminase / blood
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Aspartate Aminotransferases / blood
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Bleomycin / administration & dosage
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Bronchoalveolar Lavage Fluid / chemistry
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Creatinine / blood
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Dihydropyridines / administration & dosage
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Dihydropyridines / chemical synthesis
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Dihydropyridines / therapeutic use
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Disease Models, Animal
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Hydroxyproline / chemistry
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Intubation, Intratracheal
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L-Lactate Dehydrogenase / blood
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Lung / drug effects
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Lung / pathology
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Male
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Molecular Structure
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Pulmonary Fibrosis / blood
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Pulmonary Fibrosis / chemically induced
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Pulmonary Fibrosis / drug therapy*
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Pyridones / administration & dosage
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / therapeutic use*
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Rats
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Time Factors
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Urea / blood
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Dihydropyridines
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Pyridones
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Bleomycin
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Urea
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Creatinine
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pirfenidone
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L-Lactate Dehydrogenase
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Aspartate Aminotransferases
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Alanine Transaminase
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Hydroxyproline