Synthesis and pharmacological characterization of a potent, orally active p38 kinase inhibitor

J Dumas, H Hatoum-Mokdad, RN Sibley…

Index: Dumas, Jacques; Hatoum-Mokdad, Holia; Sibley, Robert N; Smith, Roger A; Scott, William J; Khire, Uday; Lee, Wendy; Wood, Jill; Wolanin, Donald; Cooley, Jeffrey; Bankston, Donald; Redman, Aniko M; Schoenleber, Robert; Caringal, Yolanda; Gunn, David; Romero, Romulo; Osterhout, Martin; Paulsen, Holger; Housley, Timothy J; Wilhelm, Scott M; Pirro, John; Chien, Du-Shieng; Ranges, Gerald E; Shrikhande, Alka; Muzsi, Andrew; Bortolon, Elizabeth; Wakefield, Jean; Gianpaolo Ostravage, Cynthia; Bhargava, Ajay; Chau, Thuy Bioorganic and medicinal chemistry letters, 2002 , vol. 12, # 12 p. 1559 - 1562

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Citation Number: 38

Abstract

Inhibitors of the MAP kinase p38 provide a novel approach for the treatment of osteoporosis, inflammatory disorders, and cancer. We have identified N-(3-tert-butyl-1-methyl-5-pyrazolyl)- N′-(4-(4-pyridinylmethyl) phenyl) urea as a potent and selective p38 kinase inhibitor in biochemical and cellular assays. This compound is orally active in two acute models of cytokine release (TNF-induced IL-6 and LPS-induced TNF) and a chronic model of ...