Philip Stephen Jones

Identification of a novel class of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents with protein tyrosine phosphatase inhibitory activity.

A novel series of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents have been identified. These compounds show non-selective inhibitory properties against a panel of protein tyrosine phosphatases including PTP1B. Compounds 12 and 13 display oral glucose lowering effects in ob/ob mice.

New building blocks for the assembly of sequence selective molecular zippers

Synthetic H-bonded molecular zippers contain no sequence information that can be used to engineer the selective binding interactions characteristic of biopolymers; reversing the sense of the amide bonds in the two binding partners generates a new orthogonal recognition motif and the mutually complementary binding partners form complexes an order of magnitude more stable than the corresponding mismatch complexes.

Changing methods for discovering antiviral drugs.

Viral diseases were largely untreatable 40 yr ago. Now effective and safe therapies are available. This has led to significant improvements in the quality of life for large numbers of patients. New viral diseases are, however, continuing to emerge and established viruses have been shown to develop resistance to available therapies making this a fertile area for continued drug discovery. The processes used to discover drugs have also changed enormously over the past 40 yr. Nowhere have these changes been more apparent than in the field of antiviral therapy. Therefore, the development of antiviral drugs makes an excellent example for documenting the changes in approaches used to discover active agents. This brief chapter describes some of these changes-from the broad screening in animals and tissue culture first used to the mechanism-based approaches using computer assisted techniques and biostructural information.