254905-69-6Relevant articles and documents
Compounds with growth hormone releasing properties
-
, (2008/06/13)
Disclosed are compounds of formula I formula I wherein R1, R2, R5, R6, R7, R8, G, J, L, M, a, b, c, d, e, and f are as defined in the specification, and compositions containing them. These
The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency
Peschke, Bernd,Ankersen, Michael,Bauer, Michael,Hansen, Thomas Kruse,Hansen, Birgit Sehested,Nielsen, Karin Kramer,Raun, Kirsten,Richter, Lutz,Westergaard, Lisbet
, p. 487 - 501 (2007/10/03)
In order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a Cmax of over 40 ng mL-1.
