Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues

James J Li; Haixia Wang; Fucheng Qu; Christa Musial; Joseph A Tino; Jeffrey A Robl; Dorothy Slusarchyk; Rajasree Golla; Ramakrishna Seethala; Kenneth Dickinson; Leah Giupponi; Gary Grover; Paul Sleph; Neil Flynn; Brian J Murphy; David Gordon; Melissa Kung; Robert Stoffel

doi:10.1016/j.bmcl.2005.02.040

Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues

Bioorg Med Chem Lett. 2005 Apr 1;15(7):1799-802. doi: 10.1016/j.bmcl.2005.02.040.

Authors

James J Li¹, Haixia Wang, Fucheng Qu, Christa Musial, Joseph A Tino, Jeffrey A Robl, Dorothy Slusarchyk, Rajasree Golla, Ramakrishna Seethala, Kenneth Dickinson, Leah Giupponi, Gary Grover, Paul Sleph, Neil Flynn, Brian J Murphy, David Gordon, Melissa Kung, Robert Stoffel

Affiliation

¹ Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543, USA.

PMID: 15780609
DOI: 10.1016/j.bmcl.2005.02.040

Abstract

Several novel series of tetrahydroisoquinoline 1-carboxamides were prepared and shown to be potent growth hormone (GH) secretagogues. Among them, carbamate 12a-E2 displays excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model.

MeSH terms

Animals
Growth Hormone / blood
Growth Hormone / metabolism*
Hydrophobic and Hydrophilic Interactions
Models, Chemical
Oligopeptides / chemical synthesis*
Oligopeptides / pharmacology
Rats
Receptors, G-Protein-Coupled / blood
Receptors, G-Protein-Coupled / metabolism*
Receptors, Ghrelin
Tetrahydroisoquinolines / chemical synthesis
Tetrahydroisoquinolines / pharmacology

Substances

Oligopeptides
Receptors, G-Protein-Coupled
Receptors, Ghrelin
Tetrahydroisoquinolines
growth hormone releasing hexapeptide
Growth Hormone