Allosteric modulators of the adenosine A1 receptor: synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes

Luigi Aurelio; Celine Valant; Bernard L Flynn; Patrick M Sexton; Arthur Christopoulos; Peter J Scammells

doi:10.1021/jm9002582

Allosteric modulators of the adenosine A1 receptor: synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes

J Med Chem. 2009 Jul 23;52(14):4543-7. doi: 10.1021/jm9002582.

Authors

Luigi Aurelio¹, Celine Valant, Bernard L Flynn, Patrick M Sexton, Arthur Christopoulos, Peter J Scammells

Affiliation

¹ Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

PMID: 19514747
DOI: 10.1021/jm9002582

Abstract

A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A(1)AR-mediated phosphorylation of ERK1/2 in intact CHO cells to identify both potential agonistic effects as well the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. More detailed concentration-response experiments were subsequently performed on two compounds (9a and 9o) utilizing both the ERK1/2 assay as well as a second assay of [(35)S]GTPgammaS binding to activated G proteins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / analogs & derivatives
Adenosine / pharmacology
Adenosine A1 Receptor Agonists*
Adenosine A1 Receptor Antagonists*
Allosteric Regulation
Animals
CHO Cells
Cricetinae
Cricetulus
Extracellular Signal-Regulated MAP Kinases / metabolism
Humans
Phosphorylation / drug effects
Thiophenes / chemistry*
Thiophenes / pharmacology*

Substances

Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Thiophenes
N-(1-methyl-2-phenylethyl)adenosine
Extracellular Signal-Regulated MAP Kinases
Adenosine