3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.

doi:10.1021/JM00170A007

Paper

3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.

Published Aug 1, 1990 · J. Macor, C. A. Burkhart, J. Heym

Journal of medicinal chemistry

Q1 SJR score

153

Citations

3

Influential Citations

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Abstract

The synthesis and in vitro and in vivo characteristics of 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1, CP-93,129) are described. This rotationally restricted phenolic analogue of RU-24,969 is a potent (15 nM) and selective (200x vs the 5-HT1A receptor, 150x vs the 5HT1D receptor) functional agonist for the 5-HT1B receptor. Direct infusion of 1 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regulating feeding behavior in rodents. 3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1) has also been shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor. The source of the selectivity of 1 appears to lie in the ability of a pyrrolo[3,2-b]pyrid-5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole.

In Vitro Study

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3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one is a potent and selective serotonin (5-HT1B) agonist, inhibiting food intake in rats and demonstrating its role in regulating feeding behavior

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.

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References

Citations

Functional characterization of 5-HT1A and 5-HT1B serotonin receptor signaling through G-protein-activated inwardly rectifying K+ channels in a fluorescence-based membrane potential assay.

This study demonstrates a high-throughput assay for analyzing 5-HT1A and 5-HT1B receptor signaling through G-protein-activated inwardly rectifying K+ channels, potentially identifying novel modulators for these receptors.

Effects of a 5-HT1B Receptor Agonist on Locomotion and Reinstatement of Cocaine-Conditioned Place Preference after Abstinence from Repeated Injections in Mice

CP94253 reduces sensitized locomotion and reinstatement of cocaine-conditioned place preference in mice after repeated injections, suggesting potential as anti-cocaine medications.

Dopamine D3 and 5-HT1B receptor dysregulation as a result of psychostimulant intake and forced abstinence: Implications for medications development

Targeting dopamine D3 and serotonin 5-HT1B receptors in psychostimulant dependence may improve treatment outcomes, but side effects and treatment stages should be considered.

Development of novel serotonin 5-HT6 and dopamine D2 receptor ligands and MAO A inhibitors - Synthesis, structure-activity relationships and pharmacological characterization

This study identified three novel antidepressants, 5-HT6 agonist 81, dual DA D2 antagonist/SERT inhibitor 158, and MAO A inhibitor 134, as potential treatments for depression.

DESCENDING CONTROL IN SENSITIZATION OF REFLEXES IN THE RAT

Sensitization of hindlimb reflexes in rats is influenced by a balance of descending facilitatory and inhibitory pathways, mediated by serotonergic 5-HT3 receptors and noradrenergic 2-adrenoceptors.

Serotonergic modulation of neuronal activity in rat midbrain periaqueductal gray.

5-HT(1A) and 5-HT(1B/D) ligands partially overlap in inhibitory effects on membrane excitability and synaptic transmission within the periaqueductal gray, but 5-HT(2A/C) actions are functionally opposite in specific subregions.

Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.

Novel pyrrolidine-2,5-dione derivatives show potential as antidepressant agents due to their high affinity for 5-HT1A receptor and serotonin transporter protein.

Structure-activity relationship of 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole analogues as 5-HT(6) receptor agonists.

Substituents at the indole N 1, 2, and 5 positions influence the affinity and intrinsic activity of 5-HT6 receptors, leading to antagonists, partial agonists, and full agonists.