1378928-84-7Relevant articles and documents
A new class of highly potent matrix metalloproteinase inhibitors based on triazole-Substituted hydroxamates: (Radio)synthesis and in vitro and first in vivo evaluation
Hugenberg, Verena,Breyholz, Hans-J?rg,Riemann, Burkhard,Hermann, Sven,Schober, Otmar,Sch?fers, Michael,Gangadharmath, Umesh,Mocharla, Vani,Kolb, Hartmuth,Walsh, Joseph,Zhang, Wei,Kopka, Klaus,Wagner, Stefan
, p. 4714 - 4727 (2012/07/28)
In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., 18F) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its 18F-labeled version to yield the potential PET radioligand [18F]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.