925463-12-3Relevant articles and documents
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.
