The Role of Five-Membered Aromatic Rings Containing N and O in Modulating Bile Acid Receptors: An Overview

Over the past decades extensive scientific research in the fields of chemistry and pharmaceuticalchemistry has led to the synthesis and study of numerous chemical compounds with diverse therapeuticapplications. Many of these compounds feature heterocyclic aromatic structures, including four-, five-, and six-membered rings. Among them, five-membered heteroaromatic rings have garnered particular attention inmedicinal chemistry due to their favorable properties, such as enhanced metabolic stability, solubility, andbioavailability, key attributes for the development of effective drugs. The distinctive physicochemical propertiesand biological activities of five-membered heterocycles have established them as vital structural motifs innumerous clinically effective drugs. These heterocyclic compounds play a crucial role in the design of therapeuticagents, including those targeting bile acid receptors. Bile acid receptor modulators, activated by endogenous bileacids, offer promising potential in treating a variety of metabolic and enterohepatic disorders, such asdyslipidemia, diabetes, cholestasis, and inflammatory bowel disease.This review aims to provide an up-to-date overview of aromatic five-membered nitrogen- and oxygen-containingheterocycles, focusing on their role as bile acid receptor modulators, particularly FXR and/or GPBAR1. Thesereceptors are clinically validated targets for the treatment of metabolic disorders and non-alcoholic steatohepatitis (NASH).