Preparation of compounds containing azepine-based ring systems as bromodomain-containing protein inhibitors and therapeutic uses thereof

Abstract

The present invention relates to compds. of general formula I (wherein X and Y are O or N, with at least one being O; R1 is H, alkyl, alkenyl, etc.; Ring A is cycloalkyl, aryl, heteroaryl, or heterocycloalkyl; Rc is alkenyl, alkyl, aryl, etc.; R2 and R3 are independently H, halo, (un)substituted alkyl, etc., or R2 and R3 together form part of a spiro-fused ring; L1 is a covalent bond or (un)substituted bivalent C1-6 chain; each R5 is independently halo, CN, NO2, etc.; n = 0-5) useful as inhibitors of bromodomain-contg. proteins. The invention also provides pharmaceutically acceptable compns. comprising compds. of the present invention and methods of using said compns. in the treatment of various disorders, including proliferative disorders, inflammatory disease, sepsis, autoimmune disease, or viral infection. Synthetic procedures for prepg. I are exemplified. Example compd. II, prepd. by cyclization of the corresponding methanone intermediate, had an IC50 of < 0.05 μM in a BRD4 AlphaLisa binding assay. [on SciFinder(R)]