Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues
- 作者：Britta Evers ; Gerd Ruehter ; Martina Berg ; Jeffrey A. Dodge ; Dirk Hankotius ; Ulrike Hary ; Louis N. Jungheim ; Hans-Juergen Mest ; Eva-Maria Martin de la Nava ; Michael Mohr et al.
- 关键词：Growth hormone ; Growth hormone secretagogue
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2005
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：2005
- 卷：13
- 期：24
- 页码：6748-6762
- 文件大小：251 K
摘要
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.