title: Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect.
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.
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59, H-1025 Budapest, Hungary.
authors.forename: Daniella
authors.initials: D
authors.lastname: Takács
authors.forename: Orsolya
authors.initials: O
authors.lastname: Egyed
authors.forename: László
authors.initials: L
authors.lastname: Drahos
authors.forename: Pál
authors.initials: P
authors.lastname: Szabó
authors.forename: Katalin
authors.initials: K
authors.lastname: Jemnitz
authors.forename: Mónika
authors.initials: M
authors.lastname: Szabó
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Veres
authors.forename: Júlia
authors.initials: J
authors.lastname: Visy
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Riedl
authors.forename: György
authors.initials: G
authors.lastname: Hajós
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000586:Amination; D000818:Animals; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010640:Phenothiazines; D013450:Sulfones; D013454:Sulfoxides