Hypoglycemic and Analgesic Effects of Benzyloxyphenylpropanoic Derivatives of Isobornylamine as FFAR‐1 Agonists

Type 2 diabetes mellitus (T2DM) is considered the "pandemic of the 21st century." It is a complex multifactorial disease associated with chronic hyperglycemia, causing further complications that result in disability and early mortality. Due to the fact that the main focus of T2DM therapy is to reduce the patient's blood sugar levels, avoiding drug-induced hypoglycemia is important. Free fatty acid receptor 1 (FFAR1) agonists are considered promising hypoglycemic agents without the risk of hypoglycemia. In the future, FFAR1 agonists may expand the range of safer hypoglycemic agents with a mechanism of action not currently used in T2DM therapy. In this study, the hypoglycemic effect of a novel and potent FFAR1 agonist based on benzyloxyphenylpropanoic acid's core containing an aminobornyl fragment was investigated in a long-term experiment on C57BL/6 Ay/a (Agouti Yellow) mice. The results demonstrated a reduction in insulin resistance, attributed to the hepatoprotective effect of the compound. Additionally, the analgesic effect of the compound was evaluated in experimental pain models. It appeared that the compound exhibited a moderate analgesic effect at high doses. Furthermore, the FFAR1-mediated mechanism of action was confirmed through experiments with an FFAR1 antagonist coadministration, which suppressed both hypoglycemic and analgesic effects.