Carbamido peptide aminopeptidase N inhibitor and application thereof

Abstract

The invention provides a carbamido peptide aminopeptidase N inhibitor and application thereof. The invention provides the superactive peptide aminopeptidase N inhibitor, thereby being capable of curing the disease that the activity or the express of the aminopeptidase N is abnormal. Specifically, the invention relates to a peptide compound with the structures of general formulas (I), (II) or (III), and further relates to various optical isomers thereof, a pharmaceutically acceptable salt, a solvate and a prodrug. The invention further relates to a drug composite of the peptide compound which comprises the structures of the general formulas (I), (II) or (III) and use therefore for preparing the drug.

Description

technical field The invention relates to a ureido-peptide aminopeptidase N inhibitor, a preparation method and application thereof, and belongs to the field of chemical technology. Background technique Aminopeptidase N (APN, CD13) is a type II membrane-bound glycoprotein with a molecular weight of about 150Kd, belonging to the Gluzincins subfamily of the zinc ion-dependent metalloprotease and aminopeptidase M1 family, and exists in the form of homodimers In the cell membrane, it participates in the degradation of the N-terminal amino acid of the substrate. Aminopeptidase N is widely distributed in GM-SCF and myeloid cells at various stages of development; in non-blood cells, stromal cells distributed in hematopoietic organs, tumor vascular endothelial cells, various epithelial cells including renal proximal tubule epithelial cells, bile duct epithelial cells And small intestinal brush border epithelial cells, etc.; also distributed on the surface of fibroblasts, mesenchymal...

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Problems solved by technology

5) Aminopeptidase N participates in the degradation of endogenous analgesic substances endorphins and enkephalins, thereby causing excessive release of substance P, leading to pain

In addition, most of the inhibitors of aminopeptidase N in clinical or preclinical studies are natural products. For example, Ubenimex (Ubenimex), as a dipeptide-like structure containing β-amino acids, is currently used as an immune enhancer. For the treatment of leukemia, it is isolated from the culture fluid of Streptomyces olivorecticuli, and the total synthesis is expensive, so the source is limited

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