title: Synthesis of some novel androstanes as potential aromatase inhibitors.
abstract: Novel pyrazole and isoxazole derivatives (6-9) were synthesized as a aromatase inhibitors. Pyrazole was synthesized from hydrazine hydrate and isoxazoles from hydroxylamine hydrochloride under different conditions. Molecular docking studies were carried out for the synthesized compounds. The best score was obtained for the compound (9) followed by compound (6) while compound (8) afforded poorest of the score. Aromatase inhibitory activity for compound (6) having pyrazole ring at 2,3 position showed highest activity followed by nitrile derivative (9). Isomeric forms of isoxazole (7 and 8) showed very poor activity compared to fadrozole and aminoglutethimide. Preliminary kinetic studies have shown that both of the active compounds (6 and 9) are reversible inhibitors of the enzyme.
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara 390 001, Gujarat, India. mryadav11@yahoo.co.in
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
authors.forename: Prafulla M
authors.initials: PM
authors.lastname: Sabale
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
authors.forename: Christina
authors.initials: C
authors.lastname: Zimmer
authors.forename: Jorg
authors.initials: J
authors.lastname: Haupenthal
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000731:Androstanes / Q000138:chemical synthesis* / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles; D007700:Kinetics; D011485:Protein Binding; D011720:Pyrazoles; D013329:Structure-Activity Relationship
chemical_list: D000731:Androstanes; D047072:Aromatase Inhibitors; D007555:Isoxazoles; D011720:Pyrazoles; C031280:pyrazole