Oleanolic acid derivative, preparation method and application thereof

Abstract

The application belongs to the technical field of medicament synthesis, and particularly relates to an oleanolic acid derivative, a preparation method and application thereof. The invention claims theoleanolic acid derivative which is as shown in general formula (I), or a corresponding isomer, a non-corresponding isomer, medically acceptable salt, prodrug and active metabolite, and a mixture thereof, wherein R is selected from an aryl or heteroaryl which is optionally substituted by any one or more groups of a hydrogen atom, X, alkyl, substituted alkyl, alkoxyl or heteroaryl. The oleanolic acid derivative is obtained by performing chemical modifying on a natural product oleanolic acid serving as a lead compound, and is novel in structure, high in bioavailability and high in bioactivity. In vitro pharmacological experiments show that the oleanolic acid derivative is a noncompetitive alpha-glucosidase inhibitor, which has an obvious effect on inhibiting the activity of the alpha-glucosidase inhibitor; the activity of the oleanolic acid derivative is far higher than that of a positive drug, namely, acarbose, and has a very upbeat prospect in the application of a hypoglycemic drug.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to an oleanolic acid derivative and its preparation method and application. Background technique [0002] Diabetes mellitus (DM) is a syndrome of metabolic disorders of fat, sugar, electrolyte and protein caused by immune dysfunction, genetic factors, microbial infection and other factors leading to hypofunction of pancreatic islets. The main symptoms are polydipsia, polyphagia, Polyuria, weight loss, etc. [0003] The main harm of diabetes is not itself but the various serious complications caused by it. The complications caused by diabetes mainly include limb gangrene, blindness, cardiovascular and cerebrovascular sclerosis and renal failure. Studies have shown that 30% to 40% of patients with diabetes will develop at least one complication 10 years after the onset of diabetes. Such a high complication rate leads to high mortality and disability in diabetic pat...

AI Technical Summary

Problems solved by technology

[0007] However, as a widely distributed and cheap and easy-to-obtain natural product, its biological activity is weak, and its bioavailability is low due to its poor water solubility and poor lipid-water distribution coefficient.

Therefore, in recent years, in order to improve the bioavailability and biological activity of oleanolic acid, domestic and foreign researchers have modified its active group and active site, synthesized a series of derivatives and carried out anti-tumor, anti- HIV and other activity studies, but there are few studies on the hypoglycemic activity of such derivatives

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