title: Design, synthesis and characterization of N', N"-diaryl ureas as p38 kinase inhibitors.
abstract: Kinases have been known as important molecular targets for various diseases and p38 kinase is found to be vital target among all mitogen activated protein kinases for inflammatory diseases. P38 kinase inhibitors bearing urea scaffold have shown potent kinase inhibitory activity and also selectivity over other kinases. We present here the synthesis, p38 kinase inhibitory and anti-inflammatory activities of compounds containing N', N"-diarylurea scaffold. Compound 7f demonstrated IC50 value of 1.09 μM in p38 kinase assay and 79.41% inhibition of rat paw edema at the 2nd hour of carrageenan challenge. The molecular docking studies of synthesized compounds indicated some of the important hydrogen bonding interactions and also revealed the minor change in the binding pose when compared to BIRB796.
authors.affiliation: SVERI's College of Pharmacy, Gopalpur Road, Pandharpur-413 304, Maharashtra State India. ravigk2000@gmail.com
authors.forename: Ravindra G
authors.initials: RG
authors.lastname: Kulkarni
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Mangannavar
authors.forename: Achaiah
authors.initials: A
authors.lastname: Garlapati
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D014508:Urea; D048051:p38 Mitogen-Activated Protein Kinases