Comparison of anti-aggregatory activities of 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole

doi:10.1134/S1990747811030032

Paper

Comparison of anti-aggregatory activities of 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole

Published Aug 23, 2011 · O. Demina, A. Laptev, A. Lukin

Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology

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Abstract

Two bioisosteric analogs, 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole, were synthesized so as to compare their antiaggregatory activities, to determine a pharmacologically active fragment in molecules of this type, and to explore the mechanisms of action of potential antiag-gregatory compounds belonging to the class of 3,5-substituted isoxazoles. Antiaggregatory activities of these compounds were studied in vitro using three aggregation inducers, such as arachidonic acid, adenosine diphosphate, and adrenaline. It was shown that 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole and 5-phenyl-3-(3-pyridyl)isoxazole completely suppressed platelet aggregation induced by arachidonic acid and the second wave of platelet aggregation induced by adrenaline or adenosine diphosphate. The antiaggregatory activity of substituted isoxasole was 1.1–1.5 times higher than that of substituted oxadiazole. In contrast to the isoxazole analog, 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole in concentrations of 300–400 μM partially suppressed the first wave of aggregation induced by adenosine diphosphate. It was demonstrated that both compounds were not thrombin inhibitors in vitro at concentrations up to 250 μM. Thus, introduction of a nitrogen atom into the C4-position of the isoxazole ring changes the molecule properties. It suggests that the pharmacophoric fragment of the molecule should be the whole isoxazole or 1,2,4-oxadiazole ring but not a part of the ring as was supposed previously.

In Vitro Study

Study Snapshot

Both 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole effectively suppress platelet aggregation, suggesting their potential as antiag-gregatory compounds.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Comparison of anti-aggregatory activities of 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole

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References

PLATELETS IN HEMATOLOGIC AND CARDIOVASCULAR DISORDERS: A CLINICAL HANDBOOK

This clinical handbook provides a comprehensive overview of platelets in hematologic and cardiovascular disorders, covering platelet function, coagulation, and antiplatelet therapy.

Development of dual-acting benzofurans for thromboxane A2 receptor antagonist and prostacyclin receptor agonist: synthesis, structure-activity relationship, and evaluation of benzofuran derivatives.

The novel series of benzofurans show potential as dual-acting antithrombotic agents by blocking thromboxane A2 receptor and activating prostacyclin receptor, offering potential for novel treatments without hypotensive side effects.

P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms.

Both P2Y(1) and P2Y(12) receptors desensitize in human platelets, with P2Y(12) desensitization mediated by GRKs and P2Y(1) largely dependent on protein kinase C activity.

NMR structure of the thromboxane A2 receptor ligand recognition pocket.

The thromboxane A2 receptor's ligand recognition pocket is shaped by the second extracellular loop and disulfide bond, which can be applied to other prostanoid receptors and GPCRs.

Different G protein‐coupled signaling pathways are involved in α granule release from human platelets

Alpha granule release from platelets occurs through costimulation of Gq and Gi signaling pathways, with P2Y12 receptors playing a key role in thromboxane A2 release.

Antithrombotic effects of S 18886, a novel orally active thromboxane A2 receptor antagonist

S 18886, a novel orally active thromboxane A2 receptor antagonist, shows dose-dependent antithrombotic effects, with similar effects to clopidogrel and superior to aspirin in preventing atherothrombotic complications.

The Thromboxane Receptor Antagonist PBT-3, a Hepoxilin Stable Analog, Selectively Antagonizes the TPα Isoform in Transfected COS-7 Cells

PBT-3 selectively inhibits platelet aggregation by targeting the thromboxane receptor TP isoform, with the tail playing a role in recognition.

Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst

TBAF is a mild and efficient catalyst for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles, converting alkanoyl- and aroyloxyamidines into corresponding oxadiazoles in high yield.

Citations

3-Pyridylisoxazoles as prototypes of antiaggregatory agents

5-alkyl-3-pyridylisoxazoles show antiaggregatory activity and are selective for platelet membrane receptors, with spatial constraints in position 5 of the isoxazole ring.

5-Substituted pyridylisoxazoles as effective inhibitors of platelet aggregation

5-Substituted pyridylisoxazoles effectively inhibit platelet aggregation without acting as cyclooxygenase, thromboxane synthase, or thrombin inhibitors.