Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A(1) and A(2A) receptors

R. Bansal, G. Kumar, D. Gandhi, Louise C. Young, A.L. Harvey

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Abstract

A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.
LanguageEnglish
Pages2122-2127
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number5
DOIs
Publication statusPublished - May 2009

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Xanthines
Adenosine A2A Receptors
Purinergic P1 Receptors
Adenosine
Substitution reactions
Assays
Radioligand Assay

Keywords

  • 8-Arylxanthines
  • adenosine receptor antagonists
  • radioligand binding assays
  • A(1) and A(2A) adenosine receptors

Cite this

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title = "Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A(1) and A(2A) receptors",
abstract = "A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.",
keywords = "8-Arylxanthines, adenosine receptor antagonists, radioligand binding assays, A(1) and A(2A) adenosine receptors",
author = "R. Bansal and G. Kumar and D. Gandhi and Young, {Louise C.} and A.L. Harvey",
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TY - JOUR

T1 - Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A(1) and A(2A) receptors

AU - Bansal, R.

AU - Kumar, G.

AU - Gandhi, D.

AU - Young, Louise C.

AU - Harvey, A.L.

PY - 2009/5

Y1 - 2009/5

N2 - A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.

AB - A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.

KW - 8-Arylxanthines

KW - adenosine receptor antagonists

KW - radioligand binding assays

KW - A(1) and A(2A) adenosine receptors

U2 - 10.1016/j.ejmech.2008.10.017

DO - 10.1016/j.ejmech.2008.10.017

M3 - Article

VL - 44

SP - 2122

EP - 2127

JO - European Journal of Medicinal Chemistry

T2 - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

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ER -