Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone
Britta Evers1, Gerd Ruehter, Martina Berg
1Lilly Forschung GmbH, Division of Eli Lilly Research Laboratories, Essener Bogen 7, 22419 Hamburg, Germany. Evers_Britta@lilly.com
Abstract:
A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative.
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