title: Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues.
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.
authors.affiliation: Lilly Forschung GmbH, Division of Eli Lilly Research Laboratories, Essener Bogen 7, 22419 Hamburg, Germany. Evers_Britta@lilly.com
authors.forename: Britta
authors.initials: B
authors.lastname: Evers
authors.forename: Gerd
authors.initials: G
authors.lastname: Ruehter
authors.forename: Martina
authors.initials: M
authors.lastname: Berg
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dodge
authors.forename: Dirk
authors.initials: D
authors.lastname: Hankotius
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hary
authors.forename: Louis N
authors.initials: LN
authors.lastname: Jungheim
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Mest
authors.forename: Eva-Maria Martin
authors.initials: EM
authors.lastname: de la Nava
authors.forename: Michael
authors.initials: M
authors.lastname: Mohr
authors.forename: Brian S
authors.initials: BS
authors.lastname: Muehl
authors.forename: Soenke
authors.initials: S
authors.lastname: Petersen
authors.forename: Birgit
authors.initials: B
authors.lastname: Sommer
authors.forename: Grit
authors.initials: G
authors.lastname: Riedel-Herold
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Tebbe
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Thrasher
authors.forename: Silke
authors.initials: S
authors.lastname: Voelkers
mesh_terms: D000613:Aminobutyrates / Q000737:chemistry*; D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000633:toxicity*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry* / Q000633:toxicity*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C507110:2,3-dihydroisothiazole; C507116:2,3-dimethoxy-8,9-methylenedioxy-benzo(i)phenanthridine-12-carboxylic acid; D000613:Aminobutyrates; D002264:Carboxylic Acids; D003432:Cross-Linking Reagents; D004151:Dipeptides; D010616:Phenanthrenes; D013844:Thiazoles; D012694:Serine; D013006:Growth Hormone