A Review on Farnesoid X Receptor (FXR) Modulators Focusing on Benzimidazole Scaffold

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Hepatology

Background:

• Bile acids (BAs) regulate hepatic triglyceride synthesis by activating the farnesoid X receptor (FXR).
• FXR is a key therapeutic target for liver diseases like primary biliary cholangitis and metabolic dysfunction-associated steatotic/steatohepatitis.
• Current FXR modulators face challenges with long-term administration side effects, necessitating novel drug development.

Purpose of the Study:

• To develop novel farnesoid X receptor (FXR) modulators.
• To explore benzimidazole as a core structural motif for FXR modulator drug candidates.
• To identify potential therapeutics for liver diseases with improved safety profiles.

Main Methods:

• Design and synthesis of novel compounds utilizing benzimidazole as a fused heteroaromatic ring.
• Evaluation of synthesized compounds as FXR modulators.
• Structure-activity relationship studies to optimize potency and minimize off-target effects.

Main Results:

• Successful development of FXR modulators incorporating the benzimidazole scaffold.
• Demonstration of the synthetic accessibility and versatility of benzimidazole in creating diverse FXR modulator structures.
• Identification of promising lead compounds for further preclinical development.

Conclusions:

• Benzimidazole serves as a valuable privileged structure for the development of novel FXR modulators.
• The developed compounds represent potential therapeutic candidates for liver diseases.
• Further research is warranted to optimize these candidates and assess their clinical efficacy and safety.