Tetrahydronaphthalene compound as well as pharmaceutical composition and application thereof

Abstract

The present invention provides a new tetrahydronaphthalene compound, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound, and a use of the compound or the composition in prevention and / or treatment of central nervous diseases, the compound has a structure represented by formula (I), x, Y, Z, W and R are defined in the invention.

Description

[0001] Field of Invention [0002] The present invention relates to the field of medicinal chemistry, in particular to tetralin compounds, their stereoisomers, solvates, or pharmaceutically acceptable salts, pharmaceutical compositions containing the compounds, and use of the compounds or compositions Use in the preparation of medicaments for preventing and / or treating central nervous system diseases. Background of the Invention [0003] Parkinson's disease (PD), also known as tremor palsy, is a common neurodegenerative disease characterized by progressive, multiple and insidious onset. Clinical symptoms include bradykinesia, resting tremor, Motor symptoms such as muscle stiffness and non-motor symptoms such as constipation, sleep disturbance, dysphagia, and Restless Legs Syndrome (RLS). PD is the second most common neurodegenerative disease after Alzheimer's disease. According to statistics from the National PD Foundation in 2013, there are 4 to 6 million patients worldwide....

AI Technical Summary

Problems solved by technology

However, as a transdermal preparation, local skin reactions such as erythema, dermatitis, and itching often occur, which will seriously affect patient compliance and lead to interruption of medication

Intermittent drug use may lead to repeated peaks and troughs in blood concentration, aggravate the condition, and bring more serious mental and economic burdens to patients or their families

Patent applications CN108341798 and CN109415335 disclose a long-acting prodrug derivative of rotigotine, but the melting point of the compound disclosed in the patent does not exceed 53°C. The low melting point of the compound will bring great difficulties to the large-scale preparation of the preparation. At the same time, it is also easy to cause changes in the performance of the drug during long-term storage, which in turn affects the stable release of the long-acting drug in the body, resulting in fluctuations in the effective blood drug concentration in the body, and finally makes the long-acting drug lose its long-acting effect

Images