873586-59-5Relevant academic research and scientific papers
α-Biphenylsulfonylamino 2-methylpropyl phosphonates: Enantioselective synthesis and selective inhibition of MMPs
Biasone, Alessandro,Tortorella, Paolo,Campestre, Cristina,Agamennone, Mariangela,Preziuso, Serena,Chiappini, Marika,Nuti, Elisa,Carelli, Paolo,Rossello, Armando,Mazza, Fernando,Gallina, Carlo
, p. 791 - 799 (2007/10/03)
(R)-α-Biphenylsulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, α-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA. Suzuki coupling of 9 with the desired arylboronic acids, gave the expected biphenylsulfonylamino derivatives in satisfactory yields. Liberation of the phosphonic group by hydrogenolysis led to the desired (R)-α-biphenylsulfonylamino 2-methylpropyl phosphonates 14a-i. Screening of the new compounds on MMP-1, -2, -3, -7, -8, -9, -13 and -14 showed IC50 in the range of nM in most cases.
Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates
Pochetti, Giorgio,Gavuzzo, Enrico,Campestre, Cristina,Agamennone, Mariangela,Tortorella, Paolo,Consalvi, Valerio,Gallina, Carlo,Hiller, Oliver,Tschesche, Harald,Tucker, Paul A.,Mazza, Fernando
, p. 923 - 931 (2007/10/03)
Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP in
