Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands

Ranju Bansal, Gulshan Kumar, Deepika Gandhi, Rakesh Yadav, Louise C Young, Alan L Harvey

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenyl-xanthines and their evaluation for affinity for A1 and A2 adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1,3-dimethylxanthine (6a) (K(i)= 100 nM) and 8-[(4-cyclopentyloxy)-3-methoxyphenyl] -3-methyl-1-propylxanthine (12) (K(i) = 150 nM) displayed the highest affinity at A2A receptors as well as over 1000 fold selectivity over the A1 adenosine receptor subtype.
LanguageEnglish
Pages131-136
Number of pages6
JournalArzneimittel Forschung
Volume60
Issue number3
Publication statusPublished - 2010

Fingerprint

Xanthines
Adenosine A1 Receptors
Xanthine
Adenosine
Adenosine A2 Receptors
Ligands
Radioligand Assay
Theophylline

Keywords

  • anti-asthmatic agents
  • humans
  • indicators and reagents
  • magnetic resonance spectroscopy
  • radioligand assay
  • receptor
  • spectrophotometry
  • spectroscopy
  • structure-activity relationship
  • xanthine
  • adenosine A1
  • adenosine A2A
  • infrared
  • fourier rransform infrared

Cite this

Bansal, Ranju ; Kumar, Gulshan ; Gandhi, Deepika ; Yadav, Rakesh ; Young, Louise C ; Harvey, Alan L. / Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands. In: Arzneimittel Forschung. 2010 ; Vol. 60, No. 3. pp. 131-136.
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Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands. / Bansal, Ranju; Kumar, Gulshan; Gandhi, Deepika; Yadav, Rakesh; Young, Louise C; Harvey, Alan L.

In: Arzneimittel Forschung, Vol. 60, No. 3, 2010, p. 131-136.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands

AU - Bansal, Ranju

AU - Kumar, Gulshan

AU - Gandhi, Deepika

AU - Yadav, Rakesh

AU - Young, Louise C

AU - Harvey, Alan L

PY - 2010

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AB - The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenyl-xanthines and their evaluation for affinity for A1 and A2 adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1,3-dimethylxanthine (6a) (K(i)= 100 nM) and 8-[(4-cyclopentyloxy)-3-methoxyphenyl] -3-methyl-1-propylxanthine (12) (K(i) = 150 nM) displayed the highest affinity at A2A receptors as well as over 1000 fold selectivity over the A1 adenosine receptor subtype.

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KW - indicators and reagents

KW - magnetic resonance spectroscopy

KW - radioligand assay

KW - receptor

KW - spectrophotometry

KW - spectroscopy

KW - structure-activity relationship

KW - xanthine

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KW - adenosine A2A

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KW - fourier rransform infrared

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