Tapentadol carbamate derivative and preparation method and application thereof

Abstract

The invention belongs to the field of pharmacy, in particular to a tapentadol carbamate derivative with a general formula I, pharmaceutically acceptable salts, a preparation method and an application thereof. In the invention, the structure of phenolic hydroxyl groups in tapentadol molecules is improved by a chemical synthesis method, and proper carrier groups are introduced in the position to synthesize carbamate type prodrug. All amines adopted by the carbamate are fatty amines, wherein dimethylamine or methylamine fragments can generate demethylation metabolism easily in vivo, thereby being convenient for releasing raw tapentadol. Meanwhile, the existence of the carbamate structure increases the chemical stability of the prodrug and can obviously improve the oral bioavailability, reduce the administration dosage and lower the toxic side effect, and the tapentadol carbamate derivative can be further developed into novel tapentadol analgesics.

Description

technical field The invention belongs to the field of pharmacy and relates to carbamate derivatives of tapentadol and its preparation and application. Background technique Tapentadol HCl is a new type of centrally acting analgesic drug developed by Johnson & Johnson Company of the United States with a dual mechanism of action. It is used as a single isomer of (1R, 2R), molecular formula C 14 h 24 ClNO, chemical name (1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol Hydrochloride. Tapentadol belongs to 1-phenyl-3-dimethylaminopropane compounds, which have various pharmacological activities and can be used to relieve pain (EP693475), and can also be used to treat psychosis (DE102007012165), depression (DE10233048 ), urinary incontinence (WO2002043715), etc. Tapentadol was approved for marketing by the U.S. Food and Drug Administration (FDA) on November 21, 2008. It has been clinically shown that it has good efficacy between morphine and tramadol, and can achieve...

AI Technical Summary

Problems solved by technology

This kind of carrier fragment enters the body and is difficult to metabolize and release the prodrug, and the aromatic amine structure will have unpredictable toxicity, and the druggability is extremely low

Images