Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach.

Many years of work have been invested in the identification of potent and selective COX-2 inhibitors for the treatment of chronic inflammatory pain. One issue faced by workers is the balance between the lipophilicity required for potent enzyme inhibition and the physical properties necessary for drug absorption and distribution in vivo. Frequently approaches to reduce lipophilicity through introduction of polar functionality is hampered by highly challenging chemistry to prepare key molecules. We have complemented traditional synthetic chemistry with a biotransformations approach which efficiently provided access to an array of key target molecules.

Defining and maintaining a high quality screening collection: the GSK experience.

Understanding the quality of a screening collection is the first step to improving it and, as a result, the quality of the screening process. This article outlines how this issue was approached at GlaxoSmithKline and some of the hurdles that needed to be overcome to achieve success. The article focuses specifically on the necessary software and hardware infrastructure needed, and at some of the extra benefits of such a project in terms of data mining and data modelling.