Abstract
Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration-oxidation of dienes followed by Buchwald-Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity.
Copyright © 2013. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Amination
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Animals
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Cells, Cultured
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Drug Resistance, Multiple / drug effects*
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Hepatocytes / drug effects*
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Male
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Phenothiazines / chemical synthesis
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Phenothiazines / chemistry*
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Phenothiazines / pharmacology*
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Rats
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Rats, Wistar
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Structure-Activity Relationship
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Sulfones / chemical synthesis
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Sulfones / chemistry
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Sulfones / pharmacology
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Sulfoxides / chemical synthesis
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Sulfoxides / chemistry
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Sulfoxides / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Phenothiazines
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Sulfones
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Sulfoxides