title: Synthesis and biological activities of spiroheterocyclic growth hormone secretagogues.
abstract: The synthesis and biological activities of a series of spiroheterocyclic growth hormone secretagogues are reported. Modification of the spiroindane part-structure of the prototypal secretagogue L-162,752 revealed that the spiroindane could be replaced with spirobenzodihydrothiophen derivatives to enhance not only in vitro potency but also oral activity. In this study non-aromatic D-2-amino-4-cyclohexylbutanoic analogs (8a-8d) were also identified to be active secretagogues.
authors.affiliation: Medicinal Chemistry Department, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Chen
authors.forename: P P
authors.initials: PP
authors.lastname: Pollard
authors.forename: A A
authors.initials: AA
authors.lastname: Patchett
authors.forename: K
authors.initials: K
authors.lastname: Cheng
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.forename: W W
authors.initials: WW
authors.lastname: Chan
authors.forename: B
authors.initials: B
authors.lastname: Butler
authors.forename: T M
authors.initials: TM
authors.lastname: Jacks
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
mesh_terms: D000818:Animals; D004285:Dogs; D013006:Growth Hormone / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D051381:Rats; D013141:Spiro Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D007211:Indoles; C116595:L 162752; D013141:Spiro Compounds; D013006:Growth Hormone