Identification and Pharmacological Profile of an Indane Based Series of Ghrelin Receptor Full Agonists.
Gardelli C, Wada H, Ray A, Caffrey M, Llinas A, Shamovsky I, Tholander J, Larsson J, Sivars U, Hultin L, Andersson U, Sanganee HJ, Stenvall K, Leidvik B, Gedda K, Jinton L, Rydén Landergren M, Karabelas K.
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.