title: Microwave-assisted synthesis of a pyrazolyl ketone library for evaluation as p38 MAPK inhibitors in Werner syndrome cells.
abstract: BACKGROUND
  The pyrazolyl ketone motif of RO3201195, which exhibits good oral bioavailability and high selectivity for p38 MAPK over other kinases, is a key pharmacophore that could find application in the treatment of Werner syndrome.
  
  
  CONCLUSIONS
  Microwave irradiation promotes Knoevenagel condensation of a β-ketonitrile and formamidine, to give β-aminovinyl ketones, and their subsequent cyclocondensation with a subset of hydrazines to provide rapid access to a 24-membered library of pyrazolyl ketones. The library was evaluated in human hTERT-immortalized HCA2 dermal cells and Werner syndrome cells.
  
  
  CONCLUSIONS
  Four compounds display comparable, if not slightly improved, potency over RO3201195.
authors.affiliation: School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, CF10 3AT, UK. Bagleymc@cardiff.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Bagley
authors.forename: Terence
authors.initials: T
authors.lastname: Davis
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Dix
authors.forename: Paola Gs
authors.initials: PG
authors.lastname: Murziani
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Rokicki
authors.forename: David
authors.initials: D
authors.lastname: Kipling
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008872:Microwaves; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000494:pharmacology; D014898:Werner Syndrome / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C509704:5-amino-1-(4-fluorophenyl)-4-(3-(2,3-dihydroxypropoxy)benzoyl)pyrazole; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D054852:Small Molecule Libraries; D048051:p38 Mitogen-Activated Protein Kinases