title: Novel pirfenidone analogues: synthesis of pyridin-2-ones for the treatment of pulmonary fibrosis.
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.
authors.affiliation: Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: Yousry A
authors.initials: YA
authors.lastname: Ammar
authors.forename: Magda M F
authors.initials: MM
authors.lastname: Ismail
authors.forename: Hend M
authors.initials: HM
authors.lastname: El-Sehrawi
authors.forename: Eman
authors.initials: E
authors.lastname: Noaman
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Bayomi
authors.forename: Taghreed Z
authors.initials: TZ
authors.lastname: Shawer
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001761:Bleomycin / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003404:Creatinine / Q000097:blood; D004095:Dihydropyridines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000737:chemistry; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D011658:Pulmonary Fibrosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D011728:Pyridones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D013997:Time Factors; D014508:Urea / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004095:Dihydropyridines; D011728:Pyridones; D001761:Bleomycin; D014508:Urea; D003404:Creatinine; C093844:pirfenidone; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline