Rudolf Waelchli

Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity.

Pyrrolo-pyrimidones of the general structure 1 were synthesized and evaluated for their potential as MK2 inhibitors. Potent derivatives were discovered which inhibit MK2 in the nanomolar range and show potent inhibition of cytokine release from LPS-stimulated monocytes. These derivatives were shown to inhibit phosphorylation of hsp27, a downstream target of MK2 and are modestly selective in a panel of 28 kinases.

First total synthesis of the bone resorption markers deoxypyridinoline and hydroxypyridinoline

Abstract The first total synthesis of the collagen crosslinks deoxypyridinoline 1 and hydroxypyridinoline 2 was achieved. The key intermediate, pyridine 3 served as starting material for the preparation of compounds 1 and 2 and derivatives of 1 . These compounds create optimal tools to establish a diagnostic kit for bone resorption.

Dipeptide mimetics can substitute for the receptor activation domain resulting in highly potent analogues of hPTH(1–36)

Abstract A series of hPTH(1–36) analogues were prepared to study the role of the first peptide bond between residues Ser1-Val2. Some of these analogues were found to show high affinity binding in intact opossum kidney (OK-1) cells and were very active in their ability to stimulate adenylate cyclase production in intact OK-1 cells, rat UMR 106-06 osteosarcoma cells, and SaOS-2 human osteosarcoma cells. A series of hPTH(1–36) analogues were prepared to study the role of the first peptide bond between residues Ser1-Val2. Some of these analogues were found to be very active in vitro.