TY - JOUR
T1 - N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP
AU - Rossello, Armando
AU - Nuti, Elisa
AU - Carelli, Paolo
AU - Orlandini, Elisabetta
AU - Macchia, Marco
AU - Nencetti, Susanna
AU - Zandomeneghi, Maurizio
AU - Balzano, Federica
AU - Barretta, Gloria Uccello
AU - Albini, Adriana
AU - Benelli, Roberto
AU - Cercignani, Giovanni
AU - Murphy, Gillian
AU - Balsamo, Aldo
PY - 2005/3/1
Y1 - 2005/3/1
N2 - Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R 2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.
AB - Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R 2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.
KW - Antiangiogenic agents
KW - MMP-2/MT1-MMP selective inhibitors
KW - MMP-inhibitors
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U2 - 10.1016/j.bmcl.2005.01.024
DO - 10.1016/j.bmcl.2005.01.024
M3 - Article
C2 - 15713379
AN - SCOPUS:13844324397
VL - 15
SP - 1321
EP - 1326
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 5
ER -