Synthesis and biological activity of selective azasugar-based TACE inhibitors.

A series of azasugar-based hydroxamic acid derivatives bearing 2R,3R,4R,5R-configuration is described. Compound 4c with 4,5-O-acetonide group showed excellent in vitro potency against TACE, with high selectivity over MMP-1 and moderate selectivity over MMP-3 and MMP-9.

[1]  A. H. Drummond,et al.  Processing of tumour necrosis factor-α precursor by metalloproteinases , 1994, Nature.

[2]  Synthesis and structure-activity relationships of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids as HB-EGF shedding inhibitors. , 2003, Bioorganic & medicinal chemistry.

[3]  K. Tracey,et al.  Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. , 1994, Annual review of medicine.

[4]  P. McCann,et al.  Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. , 1997, Pharmacology & therapeutics.

[5]  Hirosato Kondo,et al.  New type of metalloproteinase inhibitor: design and synthesis of new phosphonamide-based hydroxamic acids. , 2002, Journal of medicinal chemistry.

[6]  R. Bast,et al.  Regulation of tumour necrosis factor-α processing by a metalloproteinase inhibitor , 1994, Nature.

[7]  S. Nishimura,et al.  Structure--activity relationships of azasugar-based MMP/ADAM inhibitors. , 2003, Bioorganic & medicinal chemistry letters.

[8]  M. Sanner Selective dopamine D4 receptor antagonists , 1998 .

[9]  A. H. Drummond,et al.  Recent advances in matrix metalloproteinase inhibitor research , 1996 .

[10]  R. Black,et al.  Adamalysins: A Family of Metzincins Including TNF‐α Converting Enzyme (TACE) , 1999 .

[11]  James M. Chen,et al.  Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 1: Structure-based design of novel acetylenic P1' groups. , 2002, Bioorganic & medicinal chemistry letters.

[12]  Charles D. McDermott,et al.  Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases , 1997, Clinical & Experimental Metastasis.

[13]  D. Goeddel,et al.  Human tumor necrosis factor. Production, purification, and characterization. , 1985, The Journal of biological chemistry.

[14]  W A Buurman,et al.  Tumor necrosis factor: function, release and clearance. , 1996, Critical reviews in immunology.

[15]  S. Nishimura,et al.  Design, synthesis and evaluation of novel azasugar-based MMP/ADAM inhibitors. , 2003, Bioorganic & medicinal chemistry letters.

[16]  M. Ohashi,et al.  KB-R7785, a novel matrix metalloproteinase inhibitor, exerts its antidiabetic effect by inhibiting tumor necrosis factor-alpha production. , 1997, Life sciences.

[17]  E. Tindall,et al.  Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. , 1997, The New England journal of medicine.