N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

详细信息    查看全文

• 作者：Rossello ; Armando ; Nuti ; Elisa ; Carelli ; Paolo ; Orlandini ; Elisabetta ; Macchia ; Marco ; Nencetti ; Susanna ; et. al.
• 关键词：MMP-inhibitors ; MMP-2/MT1-MMP selective inhibitors ; Antiangiogenic agents
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 出版时间：March 1, 2005
• 年：2005
• 卷：15
• 期：5
• 页码：1321-1326
• 全文大小：191 K

文摘

Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R₂ 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.