1.
Bioorg Med Chem Lett
; 18(6): 2067-72, 2008 Mar 15.
Article
in English
| MEDLINE
| ID: mdl-18282707
ABSTRACT
1H-tetrazole-1-alkanenitrile SR-9g exhibits a >10-fold in vivo potency enhancement over the lead nitrile 1 and has acceptable oral bioavailability in rats and dogs. An enantiospecific synthesis of 1H-tetrazole-1-alkanenitrile nitriles 9 has been developed.
Subject(s)
Growth Hormone/metabolism , Nitriles/pharmacology , Tetrazoles/pharmacology , Administration, Oral , Animals , Biological Availability , Cytochrome P-450 Enzyme System/metabolism , Dogs , Magnetic Resonance Spectroscopy , Molecular Structure , Nitriles/chemical synthesis , Nitriles/pharmacokinetics , Pituitary Gland , Rats , Structure-Activity Relationship , Tetrazoles/chemical synthesis , Tetrazoles/pharmacokinetics
2.
Bioorg Med Chem Lett
; 17(21): 5928-33, 2007 Nov 01.
Article
in English
| MEDLINE
| ID: mdl-17869100
ABSTRACT
A novel class of Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solution and solid phase protocols for the synthesis of tetrazole based GHS have been developed.