1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.

doi:10.1021/JM00113A033

Paper

1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.

Published Sep 1, 1991 · N. Meanwell, H. R. Roth, Edward C. R. Smith

Journal of medicinal chemistry

Q1 SJR score

28

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1

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Abstract

A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives was synthesized and evaluated as inhibitors of cAMP hydrolysis by a crude human platelet phosphodiesterase preparation and as inhibitors of ADP- and collagen-induced aggregation of rabbit blood platelets. The parent structure 7a, demonstrated potent inhibitory activity that was enhanced by the introduction of alkyl, alkoxy, or halogen substituents at the 5-, 6-, 7-, and 8-positions. Methylation at N-1 or N-3 produced weaker inhibitors of cAMP PDE and platelet aggregation. 1,3,9,9a-Tetrahydro-2H-imidazo[4,5-b]quinolin-2-ones (6) were found to be equipotent with their fully oxidized congeners (7). On the basis of platelet inhibitory properties in vitro, efficacy at preventing thrombus formation in animal models of thrombosis, and a favorable hemodynamic profile, 1,3-dihydro-7,8-dimethyl-2H- imidazo[4,5-b]quinolin-2-one (7o, BMY 20844) was selected for advancement into toxicological evaluation and clinical trial. An efficient synthesis of 7o is described.

In Vitro Study

Study Snapshot

1,3-dihydro-7,8-dimethyl-2H-imidazo[4,5-b]quinolin-2-one (7o) shows potential as a selective inhibitor of platelet cAMP phosphodiesterase and induced aggregation, with potential for clinical trials.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.

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References

Citations

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The crystal structure of 4-Methoxy-2-nitrobenzonitrile is stabilized by hydrogen bond interactions and O-H and N-H intermolecular contacts.

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The developed sequential sulfonylation/desulfination reaction efficiently synthesizes 5-arylidene thiohydantoin derivatives, which exhibit fungicidal activities against B. cinerea and A. solani.

Imidazoquinolines as Diverse and Interesting Building Blocks: Review of Synthetic Methodologies

Imidazoquinolines exhibit diverse biological and pharmaceutical properties, and can be prepared using two general approaches: imidazole-ring formation or pyridine-ring one, depending on the type and position of substituents.

Facile and efficient synthesis of quinolin-2(1H)-ones via cyclization of penta-2,4-dienamides mediated by H2SO4.

This method enables the efficient synthesis of substituted quinolin-2(1H)-ones by cyclizing penta-2,4-dienamides with H2SO4, a method that involves the formation of a dicationic superelectrophile and intramolecular nucleophilic

Use of the hydantoin isostere to produce inhibitors showing selectivity toward the vesicular glutamate transporter versus the obligate exchange transporter system x(c)(-).

The hydantoin isostere effectively produces selective inhibitors of the vesicular glutamate transporter, reducing uptake without significantly inhibiting the obligate cystine-glutamate transporter.

Using Morita–Baylis–Hillman acetates of 2‐azidobenzaldehydes for the synthesis of 2‐alkoxy‐3‐cyanomethylquinolines and alkyl quinoline‐3‐carboxylates

This study developed a simple method for synthesis of 2-alkoxy-3-cyanomethylquinolines and alkyl quinoline-3-carboxylates using iminophosphorane-mediated cyclization reactions of 3-(2-azidophenyl)-2-cyanomethylpropenoates