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Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes involved in the degradation and remodeling of extracellular matrix proteins. The activities of these enzymes are well regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activities due to an imbalance in the levels of MMPs and TIMPs has(More)
Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes involved in the degradation and remodeling of extracellular matrix proteins. Under normal physiological conditions, the activities of these enzymes are well-regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activities due to an(More)
It has been reported previously that saturated terbutaline sulfate in aqueous isopropanol significantly enhances the terbutaline flux through human skin in vitro. This paper demonstrates that the effect of isopropanol on the permeant species in the formulation contributes to the flux enhancement. This demonstration is based on studies involving measurements(More)
Faldaprevir is a hepatitis C virus protease inhibitor that effectively reduces viral load in patients. Since faldaprevir exhibits slow metabolism in vitro and low clearance in vivo, metabolism was expected to be a minor clearance pathway. The human [(14)C] absorption, distribution, metabolism, and excretion study revealed that two monohydroxylated(More)
Over the past 10 years, major improvements in the performance of LC-NMR have been realized. The addition of postcolumn SPE, advances in probe technology including cryogenic probes and microcoil probes, improved solvent suppression pulse sequences, and shielded magnets with better homogeneity have all contributed to rapid advancements in this technology.(More)
Dabigatran etexilate or pradaxa, a novel oral anticoagulant, is a reversible, competitive, direct thrombin inhibitor. It is used to prevent strokes in patients with atrial fibrillation and the formation of blood clots in the veins (deep venous thrombosis) in adults who have had an operation to replace a hip or a knee. Pradaxa is the only novel oral(More)
The ability of the macrocyclic HCV protease inhibitor BILN 2061 to bind different classes of cations has been studied by (15)N, (13)C, and (1)H NMR. (15)N NMR experiments were performed at natural abundance or with isotopically labeled materials. Three classes of cations: alkali metals, alkaline earth metals, and transition metals, were examined, using two(More)
The copper-catalyzed asymmetric propargylation of cyclic aldimines is reported. The influence of the imine trimer to inhibit the reaction was identified, and equilibrium constants between the monomer and trimer were determined for general classes of imines. Asymmetric propargylation of a diverse series of N-alkyl and N-aryl aldimines was achieved with good(More)
A large-scale synthesis of the hepatitis C virus drug Faldaprevir revealed precipitation of an unknown insoluble solid from methanol solutions of the drug substance. The unknown impurity was determined to be a polymer of Faldaprevir based on analytical methods that included size exclusion chromatography in combination with electrospray ionization mass(More)
A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.