Discovery, synthesis, and structure–activity studies of tetrazole based growth hormone secretagogues

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 21; pp. 5928 - 5933
• Main Authors: Hernández, Andrés S., Cheng, Peter T.W., Musial, Christa M., Swartz, Stephen G., George, Rocco J., Grover, Gary, Slusarchyk, Dorothy, Seethala, R. Krishna, Smith, Mark, Dickinson, Kenneth, Giupponi, Leah, Longhi, Daniel A., Flynn, Neil, Murphy, Brian J., Gordon, David A., Biller, Scott A., Robl, Jeffrey A., Tino, Joseph A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Dogs; Growth Hormone - secretion; Growth hormone secretagogues; Hormones. Endocrine system; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; Tetrazole; Tetrazoles - chemical synthesis; Tetrazoles - chemistry; Tetrazoles - pharmacology; Tetrazole; Growth hormone secretagogues; Tetrazole derivatives; Nitrile; Rat; Nitrogen heterocycle; Structure activity relation; Chemical synthesis; Dog; Fissipedia; Carnivora; Aminoamide; Somatotropin releasing factor; Rodentia; Benzene derivatives; Oral administration; Bioavailability; In vitro; In vivo; α-Aminoacid; Vertebrata; Mammalia; Animal; Carboxamide; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.07.099

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. 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.