A patent update on cannabinoid receptor 1 antagonists (2015-2018)

ABSTRACT

Introduction: The endocannabinoid system is an important regulator of various physiological processes. Preclinical and clinical studies indicate that attenuation of the endocannabinoid system via antagonism of the type 1 cannabinoid receptor (CB1) is an excellent strategy to treat obesity, metabolic syndrome and associated disorders. However, centrally acting antagonists of CB1 also produce adverse effects like depression and anxiety. Current efforts are geared towards discovery and optimization of antagonists and modulators of CB1 that have limited brain penetration.

Areas covered: Several recent publications and patent applications support the development of peripherally acting CB1 receptor antagonists and modulators. In this review, recent patents and applications (2015–2018) are summarized and discussed.

Expert opinion: Approximately 30 new inventions have been reported since 2015, along with 3 recent commercial deals, highlighting the importance of this class of therapeutics. Taken together, peripherally acting CB1 receptor antagonists and modulators are an emerging class of drugs for metabolic syndrome, non-alcoholic steatohepatitis (NASH) and other important disorders where this receptor has been implicated.

KEYWORDS:

• CB1
• cannabinoid
• peripheral
• antagonist
• metabolic syndrome
• NASH
• obesity
• endocannabinoid

Article highlights

• This update is focused on patents with claims for CB1 antagonists in the years 2015-2018. Included are claims for inverse agonists, neutral antagonists, and negative allosteric modulators.

• A substantial amount of patent activity was identified, a summary of which is provided in Table 1.

• A wide variety of structures are patented. Examples of key compounds are provided in Figures 2 and 3.

• Most of the patent activity is focused on small molecule CB1 inverse agonists or neutral antagonists that are peripherally restricted.

• There is a focus on targeting metabolic diseases, most notably liver diseases and diabetes.

• This box summarizes the key points contained in the article.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors were supported by the research grants AA022235 and DK100414 to Rangan Maitra from the National Institutes of Health.