1.
J Med Chem
; 50(24): 5890-3, 2007 Nov 29.
Article
in English
| MEDLINE
| ID: mdl-17973363
ABSTRACT
A tetrazole-based peptidomimetic 2 (BMS-317180) was discovered as a human growth hormone secretagogue (GHS). Compound 2 is a potent, novel, orally effective GHS that shows an excellent safety profile in preclinical studies. The compound was advanced into clinical development.
Subject(s)
Carbamates/chemical synthesis , Growth Hormone/metabolism , Tetrazoles/chemical synthesis , Administration, Oral , Animals , Biological Availability , Carbamates/pharmacokinetics , Carbamates/pharmacology , Dogs , Esters , Growth Hormone/blood , Human Growth Hormone/metabolism , Humans , Macaca fascicularis , Rats , Solubility , Structure-Activity Relationship , Tetrazoles/pharmacokinetics , Tetrazoles/pharmacology , Water
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.
