Publications by authors named "William M Sanders"
The parabolic wave equation is solved using a finite-difference solution in depth that involves a nonuniform grid. The depth operator is discretized using Galerkin's method with asymmetric hat functions. Examples are presented to illustrate that this approach can be used to improve efficiency for problems in ocean acoustics and seismo-acoustics.
View Article and Find Full Text PDFThrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an explanation for these unanticipated results.
View Article and Find Full Text PDFStarting from a 2-amino-6-methylpyridine P1 group and following a strategy of enlarging it whilst reducing its polarity, we have developed a series of potent, moderately basic azaindoles which are intrinsically much more selective for thrombin versus trypsin. Certain pyrazinone acetamide azaindole derivatives have pharmacokinetic parameters after oral administration to dogs, or efficacy in vitro, comparable to an optimized pyrazinone acetamide 2-amino-6-methylpyridine derivative.
View Article and Find Full Text PDFArticle Synopsis
- Recent research on thrombin inhibitors is concentrating on finding compounds that are effective when taken orally and have good pharmacokinetics.
- A new approach was used to improve a specific compound framework (3-(2-phenethylamino)-6-methylpyrazinone acetamide) by modifying its main components.
- The result was the discovery of several strong thrombin inhibitors that are not only potent but also have high oral bioavailability and extended plasma half-lives.