Biphenyl amide p38 kinase inhibitors 1: Discovery and binding mode.

The biphenyl amides (BPAs) are a novel series of p38 MAP kinase inhibitors. The discovery of the series through structure-based focused screening is described, and the binding mode of the compounds is explained with reference to X-ray crystal structures.

[1]  P. Cohen,et al.  Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution. , 1998, Chemistry & biology.

[2]  Tobias Gabriel,et al.  Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development. , 2005, Current topics in medicinal chemistry.

[3]  A. Doweyko,et al.  Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions. , 2005, Current topics in medicinal chemistry.

[4]  J. Kendrew,et al.  Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. , 1999, Journal of medicinal chemistry.

[5]  J. Hynes,et al.  Small molecule p38 inhibitors: novel structural features and advances from 2002-2005. , 2005, Current topics in medicinal chemistry.

[6]  P. Bamborough,et al.  N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. , 2007, Bioorganic & medicinal chemistry letters.

[7]  E. A. O'neill,et al.  Molecular basis for p38 protein kinase inhibitor specificity. , 1998, Biochemistry.

[8]  P. Bamborough,et al.  Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR. , 2008, Bioorganic & medicinal chemistry letters.

[9]  Matthew R. Lee,et al.  MAP Kinase p38Inhibitors: Clinical Results and an Intimate Look at Their Interactions with p38α Protein , 2005 .

[10]  E. Goldsmith,et al.  Structural basis of inhibitor selectivity in MAP kinases. , 1998, Structure.

[11]  D. Zaller,et al.  Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity. , 2003 .

[12]  J. Boehm,et al.  p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases , 2003, Nature Reviews Drug Discovery.

[13]  J. Lisnock,et al.  The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. , 2003, Chemistry & biology.

[14]  D. Boschelli,et al.  SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. , 2003, Cancer research.

[15]  D. Zaller,et al.  Structural basis for p38α MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity , 2003, Nature Structural Biology.

[16]  L. Kuyper,et al.  Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. , 2000, Journal of medicinal chemistry.

[17]  P. Limburg,et al.  p38 mitogen-activated protein kinase (MAPK) in rheumatoid arthritis. , 2006, Mini reviews in medicinal chemistry.

[18]  Jerry L. Adams,et al.  A protein kinase involved in the regulation of inflammatory cytokine biosynthesis , 1994, Nature.

[19]  C. Peifer,et al.  New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. , 2006, Current topics in medicinal chemistry.

[20]  Paul R. Caron,et al.  Crystal Structure of p38 Mitogen-activated Protein Kinase* , 1996, The Journal of Biological Chemistry.