Synthesis and structure-activity relationships of 3-aryloxindoles: a new class of calcium-dependent, large conductance potassium (maxi-K) channel openers with neuroprotective properties.
作者： Piyasena Hewawasam , Matthew Erway , Sandra L. Moon , Jay Knipe , Harvey Weiner
DOI: 10.1021/JM0101850
关键词:
摘要: A series of 3-aryloxindole derivatives were synthesized and evaluated as activators the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising openers to emerge from this study (±)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trifluoromethyl)-2H-indol-2-one ((±)-8c) its 3-des-hydroxy analogue (±)-11b. individual enantiomers (±)-8c synthesized, channel-opening properties shown depend on absolute configuration single stereogenic center with efficacy (−)-8c superior that both (+)-8c racemic mixture when at a concentration 20 μM. Racemic 11b exhibited greater than either 8c or more active enantiomer evaluation. In vitro metabolic stability studies conducted (±)-11b rat liver S9 microsomal fractions revealed significant oxidative degradation two hydroxylated metaboli...
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