Vasopressin receptor antagonists: a patent summary (2018-2022)

ABSTRACT

Introduction

Arginine-vasopressin hormone (AVP) is a key regulator in many essential physiological processes. The effect of AVP is mediated through three receptors within the body, these are the G protein-coupled vasopressin receptors, namely V1a, V1b (also called V3), and V2. Numerous studies investigated the role of these receptors in certain pathological conditions; therefore, stimulation or inhibition of these receptors may be a treatment option in these diseases.

Areas covered

In this manuscript, the authors summarize recent patent activity (2018–2022) associated with vasopressin receptor antagonists (selective V1a or V2, and dual-acting V1a/V2), focusing mostly on chemical structures, their modifications, and potential clinical applications. Patent search was carried out using SciFinder, Espacenet, Patentscope, Cortellis Competitive Intelligence, and Derwent Innovation databases.

Expert opinion

In recent years, vasopressin receptor antagonists have been in the spotlight of drug discovery, especially V1a selective molecules. Publishing balovaptan as a possible treatment for autism spectrum disorder (ASD), greatly increased the interest in CNS-acting vasopressin antagonists. In addition, peripherally active selective V2 and dual-acting V1a/V2 antagonists have also been developed. Although clinical trials were unsuccessful in many cases, there is still potential in the research of vasopressin receptor antagonists as shown by several currently ongoing clinical trials.

KEYWORDS:

• antagonist
• receptor
• vasopressin
• V1a
• V1b
• V2

Article highlights

• Several centrally active selective V1a antagonist molecules have been discovered and published in recent years. Although they were not more effective than placebo in autism indications, the development of new and effective compounds in other CNS disorders is expected.

• No new patent applications have been published on selective V1b antagonists, additional optimization of the physicochemical parameters of the molecules would be required to identify promising drug candidates.

• Selective V2 antagonists may have the potential to inhibit the progression of ADPKD, and among these compounds, the focus is currently on the development of prodrugs of the FDA-approved tolvaptan.

• Further derivatives and detailed clinical trials would be needed to evaluate and better understand the role of dual-acting V1a/V2 antagonists that may improve outcomes in decompensated or acute heart failure.

Declaration of interest

All authors are employees of Gedeon Richter Plc. FB and ÉB are named inventors of the V1a receptor antagonist patent (WO2019116324) owned by Gedeon Richter Plc. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contributions

The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.