Synthesis and biological activities of phenyl piperazine- based peptidomimetic growth hormone secretagogues

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 11; pp. 1431 - 1436
• Main Authors: BARAKAT, K. J, KANG CHENG, NARGUND, R. P, CHAN, W. W.-S, BUTLER, B. S, JACKS, T. M, SCHLEIM, K. D, HORA, D. F, HICKEY, G. J, SMITH, R. G, PATCHETT, A. A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 02-06-1998
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Drug Design; Growth Hormone - metabolism; Hormones. Endocrine system; Indoles - pharmacology; Medical sciences; Molecular Mimicry; Peptides - chemistry; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - pharmacology; Pituitary Gland - cytology; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Rats; Spiro Compounds - pharmacology; Stimulation, Chemical; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - pharmacology; Fissipedia; Carnivora; Sulfonamide; Aminoamide; Nitrogen heterocycle; Peptide hormone; Oral administration; Non peptide compound; Vertebrata; Mammalia; Structure activity relation; Animal; Piperazine derivatives; Hormone releasing factor; Chemical synthesis; Dog; STH-RH
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/s0960-894x(98)00238-8

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.