58493-54-2Relevant articles and documents
Glycopyrronium bromide intermediate as well as preparation method and application thereof
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Paragraph 0078-0100, (2022/01/10)
The invention provides a glycopyrronium bromide intermediate as well as a preparation method and application thereof, and relates to the technical field of chemical synthesis. The preparation method of the glycopyrronium bromide intermediate comprises the step of carrying out transesterification reaction on methyl alpha-cyclopentyl mandelate as a raw material and 1, 4-dibromo-2-butanol under the action of a first base catalyst to obtain a glycopyrronium bromide intermediate, namely a compound 2. The preparation method of glycopyrronium bromide comprises the step of carrying out quaternization reaction on the compound 2 and dimethylamine under the action of a second base catalyst to obtain glycopyrronium bromide. The method has the advantages of cheap and easily available raw materials, avoidance of use of toxic gas bromomethane commonly used in the prior art, small environmental pollution, environment-friendliness, mild reaction conditions, easy control of the reaction process, avoidance of use of metal sodium, safe operation, high safety coefficient, great reduction of the reaction steps, production cost saving, high product yield, and high purity. A process route capable of industrially producing products with higher quality is provided.
PROCESS FOR SYNTHESIS OF GLYCOPYRRONIUM BROMIDE
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, (2018/09/26)
Provided herein are processes for preparation of glycopyrronium bromide comprising reaction of N-methylpyrrolidin-3-ol with compounds of Formula I or Formula II followed by additional steps.
Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists
Xiang, Zuojuan,Liu, Jun,Sun, Hongbin,Wen, Xiaoan
, p. 1173 - 1182 (2017/08/15)
The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.
