Several derivatives incorporating five-membered aromatic rings are described in this review as bile acid receptor modulators, particularly targeting the farnesoid X receptor and the G protein-coupled bile acid receptor 1. This review provides a comprehensive analysis of patents and literature that is useful to support researchers in the design of new lead compounds for the treatment of liver and metabolic diseases.

Over the past decades, extensive scientific research in the fields of chemistry and pharmaceutical chemistry has led to the synthesis and study of numerous chemical compounds with diverse therapeutic applications. 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 in medicinal chemistry due to their favorable properties, such as enhanced metabolic stability, solubility, and bioavailability, key attributes for the development of effective drugs. The distinctive physicochemical properties and biological activities of five-membered heterocycles have established them as vital structural motifs in numerous clinically effective drugs. These heterocyclic compounds play a crucial role in the design of therapeutic agents, including those targeting bile acid receptors. Bile acid receptor modulators, activated by endogenous bile acids, offer promising potential in treating a variety of metabolic and enterohepatic disorders, such as dyslipidemia, diabetes, cholestasis, and inflammatory bowel disease. This review aims to provide an up-to-date overview of aromatic five-membered nitrogen- and oxygen-containing heterocycles, focusing on their role as bile acid receptor modulators, particularly farnesoid X receptor and G protein-coupled bile acid receptor 1. These receptors are clinically validated targets for the treatment of metabolic disorders and nonalcoholic steatohepatitis.