What question did this study set out to answer?

Synthesize a novel series of 3-aryloxindole derivatives and evaluate their structure-activity relationships as Maxi-K channel openers with neuroprotective efficacy against stroke.

March 1, 2002Journal of Medicinal Chemistry

Synthesis and Structure−Activity Relationships of 3-Aryloxindoles: A New Class of Calcium-Dependent, Large Conductance Potassium (Maxi-K) Channel Openers with Neuroprotective Properties

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Synthesize a novel series of 3-aryloxindole derivatives and evaluate their structure-activity relationships as Maxi-K channel openers with neuroprotective efficacy against stroke.
Synthesized 3-aryloxindole analogues, separated (+/-)-8c enantiomers, and evaluated channel opening on cloned mSlo channels expressed in Xenopus laevis oocytes using electrophysiology.
Assessed in vitro metabolic stability in rat liver S9 microsomes and measured inhibition of electrically stimulated [3H]-glutamate release in rat hippocampal slices.
Evaluated cortical infarct volume reduction in spontaneously hypertensive rats subjected to permanent middle cerebral artery occlusion (MCAO) after intravenous (0.03–10 mg/kg) or intraperitoneal (10 mg/kg) administration.
Racemic compound (+/-)-11b displayed superior electrophysiological channel-opening efficacy compared to 8c enantiomers and significantly inhibited [3H]-glutamate release at 20 µM.
In the rat MCAO model, intravenous administration of (+/-)-11b at 0.03 mg/kg reduced cortical infarct volume by approximately 18% versus vehicle controls, whereas (+/-)-8c showed no significant reduction.
Intraperitoneal administration of (+/-)-11b at 10 mg/kg 2 hours post-occlusion reduced cortical infarct volume by 26% compared to vehicle controls.

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Implication

Preclinical study shows reduced cortical infarct volume in a rat stroke model, suggesting potential for Maxi-K channel openers as neuroprotective therapies.

Cite This Study

Hewawasam et al. (2002) studied this question.

synapsesocial.com/papers/6a82c5b6abc87fc4bf1e1da4 https://doi.org/10.1021/jm0101850

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Implication

Preclinical study shows reduced cortical infarct volume in a rat stroke model, suggesting potential for Maxi-K channel openers as neuroprotective therapies.

Synthesis and Structure−Activity Relationships of 3-Aryloxindoles: A New Class of Calcium-Dependent, Large Conductance Potassium (Maxi-K) Channel Openers with Neuroprotective Properties

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Discussion

Implication

Cite This Study

Synthesis and Structure−Activity Relationships of 3-Aryloxindoles: A New Class of Calcium-Dependent, Large Conductance Potassium (Maxi-K) Channel Openers with Neuroprotective Properties

Key Points

Discussion

Implication

Cite This Study

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