ABSTRACT
Introduction
Numerous chemotypes have been described over time in order to generate potent and selective 5-HT4R ligands. Both agonists and antagonists have demonstrated their interest in several disease models. This culminates with the FDA approval of tegaserod and prucalopride in the recent years.
Areas covered
This review summarizes the patent applications from 2014 to present, dedicated to the use or the description of novel 5-HT4R modulators. Several novel ligands and scaffolds have been industrially protected mainly in the field of central nervous system (CNS) pathologies as well as gastrointestinal disorders, including the combination with other drugs or for veterinary uses.
Expert opinion
The therapeutic potential of 5-HT4R modulators has been explored for several years in animal models, but also linked to potential safety issues with initial ligands. The current use of prucalopride in humans demonstrates that its toxicity is not linked to the target and that 5-HT4R modulators are safe in humans. Therefore, an important number of studies and patents has continued in the recent years to expand the use of 5-HT4R modulators, not only to treat gastrointestinal disorders, but also for CNS pathologies. This article details current efforts in this development.
Article highlights
The interest of 5-HT4R modulators have been explored in several pathologies and approved by the FDA.
The progress in the development of 5-HT4R modulators patented between 2014 and 2019 is reviewed.
The exploration of multiple chemical scaffolds has led to the discovery of several potent and selective 5-HT4R modulators.
Several 5-HT4R modulators are currently being evaluated in clinical trials.
The potential therapeutic interest of 5-HT4R modulators in combination with other drugs could lead to synergistic combined therapies.
This box summarizes 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.