HETEROARYL-CONTAINING ISOFLAVONES AS AROMATASE INHIBITORS

摘要

Compounds and methods useful for treating and prevention of cancer, particularly hormone-dependent breast cancer. Provided are compounds of formula I: wherein X is selected from O, N, S, SO, SO₂, and S(CH₂)_n, wherein n = 1 - 10; R₁ and R₂ may be the same or different and are selected from H, OH, OCH₃, OCH₂CH₃, OCH₂C₆H₅, NH₂, NHCH₃, N(CH₃)₂, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, C(CH₃)₃, NO₂, F, Cl, Br, CF₃, SH, SCH₃, SCH₂CH₃, OCOCH₃, OCOC(CH₃)₃, OCOCH₂COOH, and CN; and R₃ is a nitrogen-containing heterocyclic ring. Also provided are method for treating or preventing cancer in a subject by administering a therapeutically effective amount of a heteroaryl-containing isoflavone, or a pharmaceutically acceptable salt or prodrug thereof, to a subject in need of treatment. Also provided is a method for the synthesis of 2-substituted isoflavones by first reacting deoxybenzoins with a phase transfer catalyst to provide a 2-(alkylthio)isoflavone; second deprotecting the 2-(alkylthio)isoflavone; and third applying selective debenzylation to form the final compound.