Discovery of tetrahydrocarbazoles with potent hypoglycemic and hypolipemic activities.

A series of tetrahydrocarbazole derivatives was designed and synthesized on the basis of the AMP-activated protein kinase activator GY3. All the synthesized compounds were screened in HepG2 cell lines for glucose consumption activity and several of them showed potent glucose decreasing activity. In vivo evaluation of the hypoglycemic and hypolipemic effects indicated that 7a exhibited comparable activity with pioglitazone, but with a weaker body-weight increasing effect. The pharmacokinetic profiles of 7a were also investigated.