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The invention described in this review (WO2013030218) relates to compounds based on the quinazolin-4-one scaffold, their process of preparation and applications to inhibit the ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme (DUB), which is considered a potentially important new drug target for treating cancer and immunological disorders. Data are presented indicating that these small-molecule compounds are useful as selective and reversible inhibitors of USP7 in vitro and also in a cellular context, although the panel of other enzymes tested was limited. The synthesis strategy allows for the generation of a considerable variety of compounds, although similar properties of selective USP7 inhibition were reported for other related compound classes, thereby increasing the complexity of the patenting process. However, structural patterns that contribute to the selectivity of USP7 and other DUB enzyme inhibition are starting to emerge. Practical implications involve the treatment of cancer, neurodegenerative diseases, immunological disorders, diabetes, bone and joint diseases, cardiovascular diseases and viral and bacterial infections. The quality of these findings and a comparison to other compound classes with similar properties, as well as the potential for further development toward clinical exploitation are discussed.

Original publication

DOI

10.1517/13543776.2014.882320

Type

Journal article

Journal

Expert Opin Ther Pat

Publication Date

05/2014

Volume

24

Pages

597 - 602

Keywords

Animals, Anti-Inflammatory Agents, Non-Steroidal, Antineoplastic Agents, Humans, Immunosuppressive Agents, Patents as Topic, Protease Inhibitors, Quinazolinones, Ubiquitin Thiolesterase, Ubiquitin-Specific Peptidase 7