Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.

doi:10.1021/JM00099A012

Paper

Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.

Published Oct 16, 1992 · L. C. Meurer, R. Tolman, E. W. Chapin

Journal of medicinal chemistry

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39

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0

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Abstract

A series of alkyl- and halo-substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines were prepared using two approaches, the condensation of alpha-halocarbonyl derivatives with an aminopyrazine or the oxidation-dehydration of a [(beta-hydroxyalkyl)amino]pyrazine. These imidazo[1,2-a]pyrazines were evaluated for their binding affinity to the alpha 1, alpha 2, beta 1, and beta 2 adrenergic receptors as well as their ability to lower blood glucose in insulin resistant hyperglycemic ob/ob mice. Modifications on 8-(1-piperazinyl)imidazo[1,2-a]pyrazine (4) reduced alpha 2 binding, lowered hypoglycemic potency, and showed variations in binding to the alpha 1, beta 1, and beta 2 adrenergic receptors. In addition to 4, the 2-methyl, 3-methyl, and 5-methyl 8-(1-piperazinyl)imidazo[1,2-a]pyrazines (16k, 25m, and 16f, respectively) displayed high affinity for the alpha 2 receptor and were potent hypoglycemic agents when compared to 2-amino-7,8-dihydro-4-(1-piperazinyl)-6H-thiopyrano[3,2- d]pyrimidine (MTP-1403, 2). Receptor binding was modified by use of a 4-methylpiperazine moiety which reduced alpha 1 and beta 1 binding while retaining some hypoglycemic activity. The structure-activity relationship for heterocyclic alkyl and halo substitution on biological activity is discussed.

In Vitro Study

Study Snapshot

Substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines show high affinity for alpha 2 receptors and potent hypoglycemic activity, with variations in binding to alpha 1, beta 1, and beta 2 adrenergic receptors.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines.

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References

Citations

A comparison between Suzuki cross‐coupling reaction and direct arylation in the synthesis of new antibacterial imidazo‐pyrazines/pyridazines

The Suzuki cross-coupling reaction and direct arylation both efficiently synthesize antibacterial imidazo-pyrazines/pyridazines, with compounds 3a, 3c, 3j, k, l, and 3n showing better antibacterial activity.

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Imidazo[1,2-a]pyrazines adsorb onto silver clusters exhibit strong noncovalent interactions, with charge redistribution leading to significant orbital rearrangement in the Ag20-molecule complex.

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Ga(OTf)3-catalyzed synthesis of functionalized 2-carbonyl-imidazo[1,2-a]pyridines from ethyl -benzotriazolyl--morpholinoacetate provides a promising route for the synthesis of 3-amino