Derivatives of oleanolic acid and delta-oleanolic acid and medical application thereof

Abstract

The invention discloses derivatives of oleanolic acid and delta-oleanolic acid as pentacyclic triterpenoid novel AMPK agonists and medical application of the derivatives, and particularly relates to compounds shown as a formula I or a formula II and pharmaceutically acceptable salts or esters or solvates of the compounds. The compounds can be used for preparing AMPK agonists with activity of enhancing the phosphorylation level of AMPK and preparing drugs for preventing or treating AMPK-mediated diseases. The novel pentacyclic triterpenoid compounds disclosed by the invention have remarkable AMPK agonist activity, the activity of the novel pentacyclic triterpenoid compounds are remarkably superior to that of an acknowledged AMPK agonist AICAR, and meanwhile, the novel pentacyclic triterpenoid compounds have pharmacokinetic properties such as better oral bioavailability and the like and very good safety.

Description

technical field

[0001] The present invention relates to the field of biomedicine, and relates to novel pentacyclic triterpenoid compounds with AMPK agonistic activity, in particular to derivatives of oleanolic acid and δ-oleanolic acid and their medical applications. The present invention also relates to the use of such compounds in Use in the preparation of medicines for preventing or treating AMPK-mediated diseases and pharmaceutical compositions thereof. Background technique

[0002] AMPK (adenylate-activated protein kinase) is a key kinase that regulates energy metabolism and inflammatory responses in the body. Its phosphorylation activation can overcome insulin resistance, lower blood sugar, lower blood lipids (by inhibiting the synthesis of fatty acids and cholesterol), anti-inflammation, and anti-apoptosis. Death, anti-fibrosis, promotion of mitochondrial synthesis, enhancement of mitochondrial oxidative metabolism, anti-aging and anti-tumor, etc. (Physiol. Rev. 2009,...

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