Fused-Ring MGAT2 Inhibitor Compounds for Reduced Fat Absorption

The patent applies parameter changes by systematically modifying chemical structure parameters of MGAT2 inhibitors. Specifically, the invention changes the core ring structure from conventional options to a fused ring system comprising a 5-membered ring with one nitrogen atom fused to a 6-membered aromatic ring, with specific substituent patterns. This structural parameter optimization achieves superior MGAT2 inhibitory activity (IC50 values in the nanomolar range) while improving pharmacological profile and reducing side effects compared to existing compounds

The patent employs composite material principles by creating a complex fused ring structure that combines multiple heterocyclic components. The compound consists of a 5-membered ring containing nitrogen fused to a 6-membered aromatic ring, with specific substituents including halogen atoms, alkyl groups, and heterocyclic moieties. This composite molecular architecture achieves enhanced binding affinity to MGAT2 while optimizing pharmacokinetic properties and reducing adverse effects

The patent applies preliminary action by administering MGAT2 inhibitors before or during fat absorption in the intestine. The compounds prevent the conversion of 2-monoacylglycerol to diacylglycerol, thereby blocking subsequent triglyceride synthesis and reducing fat absorption before it can be stored. This preliminary intervention prevents excessive caloric retention and obesity development without requiring changes to dietary intake

The patent uses MGAT2 inhibitors as intermediary substances that mediate between dietary fat intake and fat storage. The compounds selectively inhibit MGAT2 enzyme activity in the intestine, which is the rate-limiting step in dietary fat resynthesis. This intermediary action reduces the efficiency of fat absorption and storage, thereby preventing obesity and related disorders while allowing normal dietary patterns to continue