Title of article :
The design, synthesis, and structure-activity relationships of a series of macrocyclic MMP inhibitors
Author/Authors :
Douglas H. Steinman، نويسنده , , Michael L. Curtin، نويسنده , , Robert B. Garland، نويسنده , , Steven K. Davidsen، نويسنده , , H. Robin Heyman، نويسنده , , James H. Holms، نويسنده , , Daniel H. Albert، نويسنده , , Terry J. Magoc، نويسنده , , Ildiko B. Nagy، نويسنده , , Patrick A. Marcotte، نويسنده , , Junling Li، نويسنده , , Douglas W. Morgan، نويسنده , , Charles Hutchins، نويسنده , , James B. Summers، نويسنده ,
Abstract :
A series of succinate-derived hydroxamic acids incorporating a macrocyclic ring were designed, synthesized, and evaluated as inhibitors of matrix metalloproteinases. The inhibitors were designed based on the published X-ray crystal structure of batimastat (1) complexed with human neutrophil collagenase (MMP-8). The synthesized compounds were shown to inhibit selected MMPs in vitro with low nanomolar potency.
