title: Synthesis of Z- and E-1-methyl-2-(1-hydroximinoethyl)-6-methoxy-3,4-dihydronaphthalene and evaluation as inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17).
abstract: The synthesis and biological evaluation of Z- and E-1-methyl-2-(1-hydroximinoethyl)-6-methoxy-3,4-dihydro-naphtha len e (Z-1 and E-1) as nonsteroidal inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17, CYP 17) is described. Z-1 and E-1 were separated by column chromatography and identified by 1H NMR. The synthesis of the key compound 3 was accomplished by a new reaction acetylating the 1-methyl-6-methoxy-3,4-dihydronaphthalene compound 2 under Friedel-Crafts conditions. Compound 2 was obtained from the 1-tetralone via Wittig reaction. Using a microsomal fraction of human testicular enzyme, Z-1 and E-1 inhibited the target enzyme only marginally.
authors.affiliation: Fachrichtung 12.1 Pharmazeutische Chemie, Universität des Saarlandes, Saarbrücken, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhuang
authors.forename: J
authors.initials: J
authors.lastname: Zapp
authors.forename: R W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007097:Imines / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: C110279:1-methyl-2-(1-hydroxyiminoethyl)-6-methoxy-3,4-dihydronaphthalene; D004791:Enzyme Inhibitors; D007097:Imines; D009281:Naphthalenes; D013254:Steroid 17-alpha-Hydroxylase