Evaluation of WO2017098421: GSK’s benzothiazine compounds as CD73 inhibitor filings

ABSTRACT

Introduction: There are considerable interests in the development of novel small-molecule CD73 inhibitors for the treatment of cancers, autoimmune diseases, precancerous syndromes, and other diseases associated with CD73 activity.

Areas covered: The application claims novel substituted benzothiadiazine derivatives as CD73 inhibitors for the treatment of cancer, precancerous syndromes, AIDS, autoimmune diseases, infections, atherosclerosis, and ischemia-reperfusion injury. Many of the exemplified compounds have pIC50 values between 5 to 8.4 against CD73.

Expert Opinion: These benzothiadiazine derivatives provide good leads for the discovery of potent CD73 inhibitors for the treatment of cancer and other diseases mediated by adenosine and its action on adenosine receptors.

KEYWORDS:

• Adenosine
• benzothiadiazines
• cancer
• CD73 inhibitors
• immunosuppression

Article highlights

• The roles of CD73

• Anti-CD73 drugs

• Small molecule CD73 inhibitors

• The benzothiadiazines as CD73 inhibitors

• The synthesis of benzothiadiazine derivatives

• Typical benzothiadiazines and their pIC₅₀ values

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper has not been funded.