title: Synthesis of novel oximes of 2-aryl-6-methoxy-3,4-dihydronaphthalene and their evaluation as inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17).
abstract: The synthesis and biological evaluation of oximes of 2-aryl-6-methoxy-3,4-dihydronaphthalene (7a, 7b, 14a, 14b) as nonsteroidal inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17, CYP 17) is described. The target compounds were synthesized and identified by 1H NMR and MS. The preparation of the key intermediates 5a and 5b was accomplished by coupling 4a and 4b with 1 (2-hydroxy-6-methoxy-3,4-dihydronaphthalene-2-trifluoromethanesulfonate) using the palladium complex Pd(PPh3)4 as catalyst. Hydrolysis of 5a and 5b in THF-HCl solution at room temperature gave the corresponding keto compounds 6a and 6b. The other important intermediates--the substituted (E)-2-methyl-ene-1-tetralones 10a and 10b--were obtained by condensation of 1-tetralone with the corresponding aromatic aldehydes (9a and 9b). Hydrogenation (H2), followed by reduction (NaBH4), and subsequent hydrolysis and elimination led to the keto compounds 13a and 13b. The title compounds, the oximes 7a, 7b and 14a, 14b were formed by reaction of hydroxylamine hydrochloride with the corresponding keto compounds. Using a microsomal fraction of human testicular enzyme, 7a, 7b, 14a, and 14b inhibited the target enzyme only marginally.
authors.affiliation: Universität des Saarlandes, Saarbrücken, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhuang
authors.forename: R W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013737:Testis / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D009281:Naphthalenes; D013254:Steroid 17-alpha-Hydroxylase