Tricyclic lactam and sultam derivatives as histone deacetylase inhibitors

Abstract

Claimed in this patent are novel tricyclic lactam and sultam derivatives, their pharmaceutically acceptable salts, a process for preparing them, medicaments containing them and their use as histone deacetylase (HDAC) inhibitors for preventing cell proliferation. Histone acetyltransferases (HATs) and HDACs modulate the acetylation status of lysine residues clustered near the N-terminal tail domains of the nucleosomal core histones, thereby affecting chromatin structure and transcription. HDAC inhibitors have been found to arrest cell growth and to induce apoptosis or differentiation in a variety of cancer cells, including colon carcinoma, T cell lymphoma and erythroleukaemic cells. Thus, the claimed compounds are stated to be useful for the treatment of clinical cancers such as haematological malignancies and solid tumours. It is disclosed that a specified compound demonstrated an inhibitory effect of 90% at 10 nM in the cell-free HDAC inhibition assay published previously.