161315-62-4Relevant articles and documents
CARBORANE HYDROXAMIC ACID MATRIX METALLOPROTEINASE AGENTS FOR BORON NEUTRON CAPTURE THERAPY
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Paragraph 0083; 0086, (2020/12/30)
Disclosed herein are novel carborane hydroxamic acid matrix metalloproteinase ("MMP") agents bearing borane-containing moieties and methods for their use in treating or preventing a disease, such as cancer and rheumatoid arthritis. In particular, disclosed herein are compounds of Formula (I) and (II) and pharmaceutically acceptable salt thereof: wherein the substituents are as described.
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
supporting information; experimental part, 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.
Novel fluorinated derivatives of the broad-spectrum MMP inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)- and (3-picolyl)-amino]-3- methyl-butanamide as potential tools for the molecular imaging of activated MMPs with PET
Wagner, Stefan,Breyholz, Hans-J?rg,Law, Marilyn P.,Faust, Andreas,H?ltke, Carsten,Schr?er, Sandra,Haufe, Günter,Levkau, Bodo,Schober, Otmar,Sch?fers, Michael,Kopka, Klaus
, p. 5752 - 5764 (2008/03/27)
An approach to the in vivo imaging of locally upregulated and activated matrix metalloproteinases (MMPs) found in many pathological processes is offered by positron emission tomography (PET). Hence, appropriate PET radioligands for MMP imaging are required. Here, we describe the syntheses of novel fluorinated MMP inhibitors (MMPIs) based on lead structures of the broad-spectrum inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)-amino]-3-methyl-butanamide (CGS 25966) and N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)-amino]-3- methyl-butanamide (CGS 27023A). Additionally, tailor-made precursor compounds for radiolabeling with the positron-emitter 18F were synthesized. All prepared hydroxamate target compounds showed high in vitro MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13. As a consequence, the promising fluorinated hydroxamic acid derivative 1f was resynthesized in its 18F-labeled version via two different procedures yielding the potential PET radioligand [18F]If. As expected, the biodistribution behavior of this novel compound and that of the more hydrophilic variant [ 18F]1j, also developed by our group, indicates that there was no tissue specific accumulation in wild-type (WT) mice.
