New Spiropiperidine Compounds Show Potent Growth Hormone Secretagogue Activity

Growth hormone (GH) plays a vital role in growth, metabolism, and maintaining healthy body composition. Deficiencies can lead to conditions like growth hormone deficiency in both children and adults, impacting overall health and quality of life. While recombinant GH injections are available, there's a continuous need for orally active compounds that can stimulate the body's natural GH production, offering a more convenient and potentially cost-effective treatment option. This study aimed to systematically explore structural modifications of known growth hormone secretagogue (GHS) scaffolds to identify novel, highly potent small molecules capable of stimulating GH release.

The systematic SAR investigations successfully identified several compounds with improved activity compared to the initial scaffold. Notably, the novel compound spiro(3H-1-benzopyran-2,3-piperidine) emerged as an exceptionally potent growth hormone secretagogue. This newly identified compound demonstrated low nanomolar in vitro activity, signifying its remarkable potency in stimulating growth hormone release from pituitary cells. This level of activity suggests that only very small concentrations are required to elicit a significant biological effect, making it a highly efficient stimulator of GH. The findings provide crucial insights into the precise structural features necessary for achieving such high potency within this class of compounds, advancing the understanding of GHS pharmacophores.