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Your search keyword '"Adenosine A1 Receptor Antagonists chemistry"' showing total 2 results
Start Over Descriptor "Adenosine A1 Receptor Antagonists chemistry" Journal chemmedchem
2 results on '"Adenosine A1 Receptor Antagonists chemistry"'

1. Synthesis and Pharmacological Evaluation of Identified and Putative Metabolites of the A 1 Adenosine Receptor Antagonist 8-Cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX).

Author

Holschbach MH, Bier D, Sihver W, Schulze A, and Neumaier B

Subjects
Adenosine A1 Receptor Antagonists chemical synthesis, Adenosine A1 Receptor Antagonists chemistry, Binding Sites drug effects, Dose-Response Relationship, Drug, Humans, Microsomes, Liver chemistry, Microsomes, Liver metabolism, Molecular Structure, Structure-Activity Relationship, Xanthines chemical synthesis, Xanthines chemistry, Adenosine A1 Receptor Antagonists metabolism, Adenosine A1 Receptor Antagonists pharmacology, Receptor, Adenosine A1 metabolism, Xanthines metabolism, Xanthines pharmacology
Abstract

The A 1 adenosine receptor (A 1 AR) antagonist [ 18 F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([ 18 F]CPFPX), used in imaging human brain A 1 ARs by positron emission tomography (PET), is stable in the brain, but rapidly undergoes transformation into one major (3-(3-fluoropropyl)-8-(3-oxocyclopenten-1-yl)-1-propylxanthine, M1) and several minor metabolites in blood. This report describes the synthesis of putative metabolites of CPFPX as standards for the identification of those metabolites. Analysis by (radio)HPLC revealed that extracts of human liver microsomes incubated with no-carrier-added (n.c.a.)[ 18 F]CPFPX contain the major metabolite, M1, as well as radioactive metabolites corresponding to derivatives functionalized at the cyclopentyl moiety, but no N1-despropyl species or metabolites resulting from functionalization of the N3-fluoropropyl chain. The putative metabolites were found to displace the binding of [ 3 H]CPFPX to the A 1 AR in pig brain cortex at K i values between 1.9 and 380 nm and the binding of [ 3 H]ZM241385 to the A 2A AR in pig striatum at K i values >180 nm. One metabolite, a derivative functionalized at the ω-position of the N1-propyl chain, showed high affinity (K i 2 nm) to and very good selectivity (>9000) for the A 1 AR., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2017
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2. Derivatives of benzimidazol-2-ylquinoline and benzimidazol-2-ylisoquinoline as selective A1 adenosine receptor antagonists with stimulant activity on human colon motility.

Author

Cosimelli B, Taliani S, Greco G, Novellino E, Sala A, Severi E, Da Settimo F, La Motta C, Pugliesi I, Antonioli L, Fornai M, Colucci R, Blandizzi C, Daniele S, Trincavelli ML, and Martini C

Subjects
Actins genetics, Actins metabolism, Adenosine A1 Receptor Antagonists chemistry, Benzimidazoles chemical synthesis, Benzimidazoles pharmacology, Humans, Isoquinolines chemical synthesis, Isoquinolines pharmacology, Muscle, Smooth drug effects, Muscle, Smooth metabolism, Receptor, Adenosine A1 metabolism, Receptor, Adenosine A2A chemistry, Receptor, Adenosine A2A metabolism, Receptor, Adenosine A3 chemistry, Receptor, Adenosine A3 metabolism, Adenosine A1 Receptor Antagonists pharmacology, Benzimidazoles chemistry, Colon drug effects, Isoquinolines chemistry, Quinolines chemistry, Quinolines pharmacology, Receptor, Adenosine A1 chemistry
Abstract

A number of quinolines and isoquinolines connected in various ways to a substituted benzimidazol-2-yl system were synthesized and evaluated as novel antagonists of adenosine receptors (ARs) by competition experiments using human A(1), A(2A), and A(3) ARs. The new compounds were designed based on derivatives of 2-(benzimidazol-2-yl)quinoxaline, previously reported as potent and selective antagonists of A(1) and A(3) ARs. Among these, 3-[4-(ethylthio)-1H-benzimidazol-2-yl]isoquinoline 4b exhibited the best combination of potency toward the A(1) AR (K(i) =1.4 nM) and selectivity against the A(2A) (K(i) >10 μM), A(2B) (K(i)>10 μM), and A(3) ARs (K(i)>1 μM). Functional experiments in circular smooth muscle preparations of isolated human colon showed that 4b behaves as a potent and selective antagonist of the A(1) AR in the neuromuscular compartment of this intestinal region. Biological and pharmacological data suggest that 4b is a suitable starting point for the development of novel agents endowed with stimulant properties on colonic activity., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2011
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