Moya Caffrey

Synthesis and evaluation of dual domain macrocyclic FKBP12 ligands.

Abstract A number of dual domain, macrocyclic FKBP12 ligands were synthesised in which the FK506 effector domain was fused to simplified FKBP12 bindings domains. The resulting macrocyclic compounds possessed moderate binding affinities for FKBP12 but showed no activity in an assay for FKBP12 dependent calcineurin inhibition.

Synthetic FKBP12 ligands. Design and synthesis of pyranose replacements.

Abstract A number of FKBP12 ligands were designed and synthesised and their affinity for FKBP12 assessed. In these ligands the pyranose ring of FK506 was replaced by other more synthetically accessible groups. The preparation of suitable intermediates for the synthesis of “dual domain” inhibitors (compounds 6a–c, 15 and 22) is also described.

Identification and Pharmacological Profile of an Indane Based Series of Ghrelin Receptor Full Agonists

Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease, and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite, and adipogenesis and for this reason was considered an important target to address catabolic conditions. We report the synthesis and properties of an indane based series of ghrelin receptor full agonists; they have been shown to generate a sustained increase of IGF-1 levels in dog and have been thoroughly investigated with respect to their functional activity.