What question did this study set out to answer?

To evaluate structure-activity relationships of the cyanoguanidine portion of benzopyranyl ATP-sensitive potassium channel openers to optimize cardioselective anti-ischemic potency over vasorelaxant effects.

August 1, 1995Journal of Medicinal Chemistry

Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion

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To evaluate structure-activity relationships of the cyanoguanidine portion of benzopyranyl ATP-sensitive potassium channel openers to optimize cardioselective anti-ischemic potency over vasorelaxant effects.
Synthesized benzopyranyl cyanoguanidine analogues with variations in spacer length, linker heteroatoms, aromatic substitutions, and cyclic urea constraints.
Assessed in vitro anti-ischemic potency, vasorelaxant activity, and mechanism of action via inhibition with ATP-sensitive potassium channel blockers including glyburide, sodium 5-hydroxydecanoate, and meclofenamic acid.
Altering the distance between the aniline nitrogen and the pendant aromatic ring or replacing the nitrogen with CH2, S, or O reduced anti-ischemic potency and selectivity.
Constraining the urea moiety into benzimidazolone or imidazolone rings maintained anti-ischemic potency while significantly improving cardiac selectivity, which spanned over three orders of magnitude in vitro.
Anti-ischemic protection was completely blocked by pre-administration of structurally diverse channel antagonists, verifying that channel activation mediates the therapeutic effect.

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Implication

Structure-activity study demonstrates enhanced cardioselective anti-ischemic action in benzopyranyl cyanoguanidines in vitro, indicating separable cardiac and vascular channel targets.

Cite This Study

Atwal et al. (1995) studied this question.

synapsesocial.com/papers/6a892f176abbd4965f28b66d https://doi.org/10.1021/jm00017a007

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Implication

Structure-activity study demonstrates enhanced cardioselective anti-ischemic action in benzopyranyl cyanoguanidines in vitro, indicating separable cardiac and vascular channel targets.

Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion

Key Points

Discussion

Implication

Cite This Study

Cardioselective Anti-Ischemic ATP-Sensitive Potassium Channel Openers. 3. Structure-Activity Studies on Benzopyranyl Cyanoguanidines; Modification of the Cyanoguanidine Portion

Key Points

Discussion

Implication

Cite This Study

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