Deuterated hydroxychloroquine derivative and pharmaceutical composition containing deuterated hydroxychloroquine derivative

Through the preparation of deuterated hydroxychloroquine derivatives, the toxic side effects and metabolites related problems of hydroxychloroquine are solved, the efficacy and safety of the drug are improved, and the pharmacodynamic and pharmacokinetic performance are achieved.

CN111995574AActive Publication Date: 2020-11-27QINGDAO MINGZHU YIDE PHARM CO LTD
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Patent Information

Application Number
CN202010888546.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2020-08-28
Publication Date
2020-11-27
Estimated Expiration
2040-08-28

AI Technical Summary

Technical Problem

Hydroxychloroquine has toxic side effects, especially retinal toxicity, which is related to the dose, and the blood concentration of its metabolite DCQ is related to the risk of adverse eye events in the patient. The blood concentration of the active metabolite DHCQ is related to the efficacy, but the drug concentration varies greatly , compounds with better pharmacodynamic/pharmacokinetic properties need to be developed.

Method used

Deuterated hydroxychloroquine derivative and its pharmaceutical composition are provided, which reduces toxic metabolites, improves pharmacodynamic and pharmacokinetic performance, improves therapeutic efficacy, and reduces toxic side effects by increasing active metabolites. This compound has better stability and drug preparation by the deuterated compound 2-{[4-(7-chloro-quinoline-4-ylamino)-pentyl]-ethyl-amino}-4D-ethanol Generation dynamics characteristics.

Benefits of technology

Deuterated hydroxychloroquine derivatives are more stable in liver microsomal enzymes, with increased active metabolites and decreased inactive metabolites, significantly improving pharmacodynamic/pharmacokinetic characteristics, improving drug efficacy, and reducing toxic side effects.

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Abstract

The invention relates to a deuterated hydroxychloroquine derivative and a pharmaceutical composition containing the deuterated hydroxychloroquine derivative. Specifically, the invention discloses a deuterated hydroxychloroquine derivative shown as a formula (I) and a pharmaceutical composition containing the deuterated hydroxychloroquine derivative or a crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof. The compound can be used for treating and / or preventing virus-related diseases, inflammatory diseases or inflammation-related diseases including autoimmune diseases, degenerative diseases, metabolic diseases, cardiovascular diseases, chronic infections, malignant diseases and the like. The deuterated hydroxychloroquine derivative has the advantages of high safety, relatively increased active metabolite, no activity, relatively reduced toxic and side effect metabolite and better pharmacodynamic / pharmacokinetic properties, and can be used as a medicinal effectivecomponent to form a medicinal composition, thereby enhancing the curative effect of the medicament and reducing the toxic and side effects of the medicament.
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