Amino biological pterin derivative and pharmaceutical use thereof

Abstract

This invention is designed to synthesize a new ramification of amido pterin that can control the NO generation in body. The detail structure refer the fig. This novel compound can inhibit selectivity the inducible NO synthetase, so it can be used in preparation of the drug to treat the disease caused by NO level increase.

Description

technical field [0001] The present invention relates to the design and synthesis of aminobiopterin derivatives that can control the excessive production of nitric oxide free radicals (abbreviated as NO) in the body, especially amino biopterin derivatives that can inhibit inducible nitric oxide synthase (abbreviated as iNOS) Biopterin derivatives are used to prepare medicines for preventing and treating various diseases caused by elevated levels of nitric oxide in the body. Background technique [0002] NO is a low molecular weight hydrophobic free radical with high reactivity. NO molecules can freely pass through the cell membrane and act on target molecules in cells. Theoretically speaking, NO exists in any part of cells and tissues, so it can Regulate a variety of cellular functions and produce a wide range of biological effects. As a chemical mediator, NO can regulate the cardiovascular system: it has the functions of maintaining the tension of vascular smooth muscle, in...

AI Technical Summary

Problems solved by technology

[0011] Although currently on BH 4 The mechanism of catalyzing NOS has not been fully studied, but relevant studies have shown that NOS can only play its role in the form of dimers, while BH 4 Plays a key role in iNOS dimer assembly and stability (Alderton WK, Cooper CE, Knowles RG, et al. Nitric Oxide Synthase: Struture, Function and Inhibition[J], Biochem J, 2001, 357: 593-615); BH 4 Can catalyze and promote various NOS to achieve maximum catalytic activity, BH in mammalian organisms 4 The more produced, the higher the catalytic activity of NOS (see: Gross SS, Levi RJ, Biol Chem, 1992, 267: 25722); cytokines, endotoxins, etc. can also induce BH 4 The reason is that there are two pathways of de novo synthesis and salvage synthesis in organisms to synthesize BH 4 , while BH 4 Like iNOS, the de novo synthesized key enzyme GTP cyclohydrolase, its expression is also induced by endotoxin or cytokines, which will increase the BH in cells 4 production and level-up

About BH 4 The study also showed that: BH 4 It is the cofactor of aromatic amino acid hydroxylase, and the hydroxylated products of these amino acids are the raw materials for the synthesis of neurotransmitters in the human body, directly inhibiting BH in the body 4 biosynthesis will inevitably cause serious side effects

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