Irreversible inhibitors of 17β-hsd1

Abstract

Compounds of formula (I), pharmaceutical compositions, or kits thereof are disclosed. A1 is C(O) or CHRz1; A2 is CH2 or O; R1 is hydrogen, (C1-C5) alkyl optionally substituted with one or more Z substituents, (C1-C5) alkoxyl optionally substituted with one or more Z substituents, (C2-C5) alkenyl optionally substituted with one or more Z substituents, (C2-C5) alkynyl optionally substituted with one or more Z substituents; (C3-C8) cycloalkyl; aryl; and heteroaryl; R2 is a heterocyclic aromatic ring having 5, 6, or 7 members consisting of: CRz2, N, S, or O, at least one of the members being N, S, or O; R3 is (C1-C5) alkyl substituted with one or more Br, Br76; I, I123, I124, or I131; m represents an integer from 0 to 2; n represents an integer from 0 to 2; yp represents an integer from 0 to 5. These inhibitors show improved inhibitory effect and metabolic stability compared to known inhibitors.