Anti-adipogenic action of a novel oxazole derivative through activation of AMPK pathway.

Obesity is a chronic disorder with multifactorial etiology, including genetic, medical, dietary and other environmental factors. Both natural and synthetic heterocyclic compounds, especially oxazoles, represent an interesting group of compounds and have gained much attention due to their remarkable biological activities. Therefore, a library of 3,3-DMAH (3,3-dimethylallylhalfordinol) inspired N-alkylated oxazole bromide salts with varied substitutions were prepared and screened using the 3T3-L1 model of adipogenesis and HFD-induced obesity model in Syrian golden hamsters. Several compounds in the synthesized series displayed remarkable anti-adipogenic potential on the differentiation of 3T3-L1 preadipocytes. Compound 19e, displayed the most potent activity of all and selected for further studies. Compound 19e inhibited mitotic clonal expansion of 3T3-L1 cells and enhanced the mitochondrial oxygen consumption rate of the cells during early phase of differentiation via AMPK activation. 19e also improved the dyslipidaemia in high calorie diet fed Syrian Golden Hamsters. Therefore, compound 19e can serve as a potential lead against adipogenesis and dyslipidaemia models and could be further investigated to affirm its significance as a drug candidate.

Ru(II)-catalyzed synthesis of poly-substituted furans via intermolecular oxidative annulation reaction of ethyl 3-oxo-3-phenylpropanoates with aryl alkynes/heteroaryl alkynes.

The oxidative annulation reaction of ethyl 3-oxo-3-phenylpropanoates with internal alkynes proceeds efficiently in the presence of a Ru(II)-catalyst, a copper oxidant and an additive such as AgSbF6 to give poly-substituted furans, which offers a novel method for the selective construction of poly-substituted furans. The reaction has wider substrate scope with simple starting materials, and the desired tetrasubstituted furans were prepared in good to excellent yields.