Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents 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 a new type of compds., which are potent anti-angiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range. An example compd. thus prepd. and studied was I.
N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP
ROSSELLO, ARMANDO;NUTI, ELISA;ORLANDINI, ELISABETTA;MACCHIA, MARCO;NENCETTI, SUSANNA;BALZANO, FEDERICA;UCCELLO BARRETTA, GLORIA;
2005-01-01
Abstract
Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents 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 a new type of compds., which are potent anti-angiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range. An example compd. thus prepd. and studied was I.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
