96865-83-7Relevant academic research and scientific papers
Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A 2A-D2 receptor heteromers
Soriano, Aroa,Ventura, Ruben,Molero, Anabel,Hoen, Rob,Casado, Vicent,Corte, Antoni,Fanelli, Francesca,Albericio, Fernando,Lluís, Carmen,Franco, Rafael,Royo, Miriam
supporting information; experimental part, p. 5590 - 5602 (2010/03/24)
Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease.Here, a family of heterobivalent ligands containing a D2R agonist and an A 2AR antagonist linked through a spacer of variable size was designed and synthesized to study A2AR-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A2AR with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A2AR-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A2AR-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.
BIOLOGICALLY-ACTIVE 1,3-DIPROPYL-8-PHENYLXANTHINE DERIVATIVES
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, (2008/06/13)
Certain functionalized congeners of 1,3-dialkylxanthine exhibit high potency and selectivity as antagonists for A 1-and A. sub.2-adenosine receptors and are suitable for attachment to probes, drug carriers, or solid supports. These derivatives are characterized by the presence of a phenyl at the 8 position para-substituted with a functionalized chain to provide high water solubility and high receptor affinity to such an extent that these compounds are suitable for use as antiallergenic, antiasthmatic, or cardiotonic drugs, central nervous system stimulants, and diuretics.
Functionalized Congeners of 1,3-Dialkylxanthines: Preparation of Analogues with High Affinity for Adenosine Receptors
Jacobson, Kenneth A.,Kirk, Kenneth L.,Padgett, William L.,Daly, John W.
, p. 1334 - 1340 (2007/10/02)
A series of functionalized congeners of 1,3-dialkylxanthines has been prepared as adenosine receptor antagonists.On the basis of high potency of 8-(p-hydroxyphenyl)-1,3-dialkylxanthines, the parent compounds were 8-phenyl> derivatives of theophylline and 1,3-dipropylxanthine.A series of analogues including esters of ethanol and N-hydroxysuccinimide, amides, a hydrazide, an acylurea, and anilides were prepared.The potency in blocking A1-adenosine receptors (inhibition of binding of N6-cyclohexyladenosine to brain membranes) and A2-adenosine receptors (inhibition of 2-chloroadenosine-elicited accumulations of cyclic AMP in brain slices) was markedly affected by structural changes distal to the primary pharmacophore (8-phenyl-1,3-dialkylxanthine).Potencies in the dipropyl series at the A1 receptor ranged from Ki values of 1.2 nM for a congener with a terminal amidoethyleneamine moiety to a Ki value of 58 nM for the parent carboxylic acid to a Ki of 96 nM for the bulky ureido congener.Certain congeners were up to 145-fold more active at A1 receptors than at A2 receptors.Various derivatives of the congeners should be useful as receptor probes and for radioidodination, avidin binding, and preparation of affinity columns.
