title: 4- and 6-(p-Sulphamoylphenyl)androstenediones: Studies of aromatase inhibitor-based oestrone sulphatase inhibition.
abstract: 4-(p-Sulphamoylphenyl)androstenedione (3) and 6alpha-p-sulphamoylphenyl analogues 12-14 were synthesised and tested as aromatase inhibitors as well as oestrone sulphatase inhibitors in human placental microsomes. All of the p-sulphamoylphenyl compounds synthesised were powerful inhibitors of aromatase with apparent K(i) values ranging between 30 and 97nM. In addition, the aromatase inhibitory activities of 6alpha-p-hydroxyphenyl compounds 9-11, which may be produced from their respective sulphamoylphenyl compounds by action of oestrone sulphatase, were also high in a range of 23 and 75nM of the K(i) values. On the other hand, all of the sulphamoylphenyl compounds were poor inhibitors of oestrone sulphatase with more than about 200microM of IC(25) values. Although the present findings of the oestrone sulphatase inhibition are disappointing, such attempts may be valuable to develop a new class of drugs having a dual function, aromatase inhibitor and oestrone sulphatase inhibitor, for the treatment of oestrogen-dependent breast cancer.
authors.affiliation: Tohoku Pharmaceutical University, 4-1 Komatsushima-4-Chome, Aobaku, Sendai 981-8558, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watari
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Madoka
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masao
authors.initials: M
authors.lastname: Nagaoka
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Numazawa
mesh_terms: D000735:Androstenedione / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D013429:Sulfatases / Q000037:antagonists & inhibitors*
chemical_list: D047072:Aromatase Inhibitors; D000735:Androstenedione; D001141:Aromatase; D013429:Sulfatases