Discovery of Tetralin Carboxamide Growth Hormone Secretagogue Receptor Antagonists via Scaffold Manipulation
- 1 December 2004
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 47 (27) , 6655-6657
- https://doi.org/10.1021/jm0491750
Abstract
A case study of rational design of an efficient, specific, and proprietary molecular scaffold based on the structure−activity relationship (SAR) information on a screening hit is described. Potent, selective, and orally bioavailable tetralin carboxamide growth hormone secretagogue receptor (GHS-R) antagonists were discovered. Union of rational design and high throughput synthesis provided a quick access to high quality chemical leads.Keywords
This publication has 11 references indexed in Scilit:
- Synthesis and biological evaluation of an orally active ghrelin agonist that stimulates food consumption and adiposity in ratsBioorganic & Medicinal Chemistry Letters, 2004
- A Planning Strategy for Diversity‐Oriented SynthesisAngewandte Chemie International Edition in English, 2003
- Antagonism of ghrelin receptor reduces food intake and body weight gain in miceGut, 2003
- Recent developments in ghrelin receptor (GHS-R1a) agonists and antagonistsExpert Opinion on Therapeutic Patents, 2002
- Role for central ghrelin in food intake and secretion profile of stomach ghrelin in ratsJournal of Endocrinology, 2002
- Molecular Properties That Influence the Oral Bioavailability of Drug CandidatesJournal of Medicinal Chemistry, 2002
- The Design of Leadlike Combinatorial LibrariesAngewandte Chemie International Edition in English, 1999
- Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settingsAdvanced Drug Delivery Reviews, 1997
- Design, synthesis, and structure-activity Relationships of a new series of .alpha.-adrenergic agonists: spiro[(1,3-diazacycylpent-1-ent)-5,2'-(1',2',3',4'-tetrahydronaphthalene)]Journal of Medicinal Chemistry, 1995
- A Novel Non-Peptidyl Growth Hormone SecretagogueHormone Research, 1993