Medicinal application of berberrubine

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The invention relates to berberrubine or a pharmacologically acceptable solvate thereof and application of the berberrubine or the solvate thereof as a therapeutic agent and particularly as a dipeptidyl peptidase-IV inhibitor.

Dipeptidyl peptidase IV (IUBMB Enzyme Nomenclature EC.3.4.14.5) is a type II membrane protein, a variety of names in the literature mentioned, including DPP4, DP4, DAP-1V, FAPP, glandular glycosides deaminase complex protein2, adenosine deaminase binding protein (ADAbp), dipeptidyl aminopeptidase IV, Xaa-Pro- dipeptidyl - aminopeptidase, Gly-Pro-lactamase naphthyl, after proline acid (postproline) dipeptidyl aminopeptidase IV, lymphocyte antigen CD26, a glycoprotein GP110, dipeptidyl peptidase IV, glycyl proline aminopeptidase, glycyl proline aminopeptidase, X- prolyl dipeptidyl-aminopeptidase, pepX, leukocyte antigen CD26, glycyl-prolyl dipeptidyl-aminopeptidase, dipeptidyl–peptide hydrolase, glycyl prolylamino peptidase dipeptide yl - aminopeptidase IV, DPP IV /CD26, aminoacyl - prolyl dipeptidyl-aminopeptidase, T cell triggering molecule Tpl03, X- 0 eight. Dipeptidyl peptidase 1 ¥ referred to as "0 herein --1 epileptic.

DPP-1V is a non-classical serine aminopeptidase from its amino-terminus of peptides and proteins (N- terminus) removing Xaa-Pro dipeptide. Some naturally occurring peptides have also been reported DPP-1V-dependent X-Gly or X-Ser dipeptide of the slow release type.

The present invention relates to inhibiting dipeptidyl peptidase -1V (Dipeptidyl peptidase IV, DPP_IV) activity of the compounds and/or pharmaceutically acceptable solvates, such compounds may be useful in the treatment of diabetes, such as type 2 diabetes, blood sugar, metabolic syndrome, hyperinsulinemia, obesity, cardiovascular diseases and disorders such as atherosclerosis, cerebrovascular diseases, central nervous system diseases or abnormalities, including schizophrenia, anxiety, depression, bi-directional, depression, insomnia disease, cognitive disorders, gastrointestinal diseases and disorders, cancer, inflammation and inflammatory diseases, respiratory system diseases and disorders, skeletal muscle abnormalities, osteoporosis, menopausal symptoms or abnormalities, such as gingivitis and periodontal disease, and various immune modulating the disease.

DPP-1V belong to the serine peptidase family, their common belonging to the family as well as DPP2, DPP8, DPP9, FAP and POP and so on. Animal model experiments show that inhibition of DPP8 / 9 causes such as anemia, alopecia, thrombocytopenia and splenomegaly toxicity. Therefore, the design and development of selective inhibitors against DPP-1V single Gerba point is important [Bhumika DP, ManJunath DG.Recentapproaches to medicinal chemistry and therapeutic potential of dipeptidylpeptidase-4 (DPP-4) inhibitors.European Journal of Medicinal Chemistry, 2014,74: 574-605], which is the novel selective inhibitor of DPP-1V developed difficult and critical point D

Accordingly, the need remains in the art a novel structure, strong activity selective DPP-1V inhibitors to meet the needs of clinical treatment.