John D. Knafels

TL;DR: The first crystal structure of a herpesvirus polymerase is presented, the Herpes Simplex Virus type 1 DNA polymerase, at 2.7 Å resolution and a novel inhibition mechanism is proposed in which a representative of a series of non-nucleosidic viral polymerase inhibitors, the 4-oxo-dihydroquinolines, binds at the polymerase active site interacting non-covalently with both the polymer enzyme and the DNA duplex.

TL;DR: 19 is identified as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species, leading to its selection as a clinical development candidate for treating type 2 diabetes.

TL;DR: It is hypothesized that a dual JAK1/TYK2 inhibitor will provide additional efficacy, while managing risk by optimizing selectivity against JAK2 driven hematopoietic changes.

TL;DR: Members of this series of LpxC inhibitors have improved solubility and free fraction when compared to compounds in the previously described biphenyl methylsulfone hydroxamate series, and they maintain superior Gram-negative antibacterial activity to comparator agents.

TL;DR: The synthesis and SAR as well as selectivity, pharmacokinetic, and infection model data for representative analogues of a novel series of potent antibacterial LpxC inhibitors represented by hydroxamic acid are presented.