2,6-disubstituted and 2,6,8-trisubstituted purines as adenosine receptor antagonists

Lisa C W Chang; Ronald F Spanjersberg; Jacobien K von Frijtag Drabbe Künzel; Thea Mulder-Krieger; Johannes Brussee; Adriaan P Ijzerman

doi:10.1021/jm050640i

2,6-disubstituted and 2,6,8-trisubstituted purines as adenosine receptor antagonists

J Med Chem. 2006 May 18;49(10):2861-7. doi: 10.1021/jm050640i.

Authors

Lisa C W Chang¹, Ronald F Spanjersberg, Jacobien K von Frijtag Drabbe Künzel, Thea Mulder-Krieger, Johannes Brussee, Adriaan P Ijzerman

Affiliation

¹ Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, P.O. Box 9502, 2300 RA Leiden, The Netherlands.

PMID: 16686529
DOI: 10.1021/jm050640i

Abstract

Purines have long been exploited as adenosine receptor antagonists. The substitution pattern about the purine ring has been well investigated, and certain criteria have become almost a prerequisite for good affinity at the adenosine A(1) receptor. The adaptation of the pharmacophore and the initial series of pyrimidines developed in an earlier publication resulted in a series of purines with an entirely new substitution pattern. One compound in particular, 8-cyclopentyl-2,6-diphenylpurine (31, LUF 5962) has been shown to be very promising with an affinity of 0.29 nM at the human adenosine A(1) receptor.

MeSH terms

Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists*
Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Agonists
Adenosine A3 Receptor Antagonists
Animals
Cell Line
Cricetinae
Cricetulus
Humans
Purines / chemical synthesis*
Purines / chemistry
Purines / pharmacology
Radioligand Assay
Structure-Activity Relationship

Substances

8-cyclopentyl-2,6-diphenylpurine
Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Agonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Agonists
Adenosine A3 Receptor Antagonists
Purines