525-66-6Relevant articles and documents
An in-vitro and in-vivo correlative approach to the evaluation of ester prodrugs to improve oral-delivery of propranolol
Shameem,Imai,Otagiri
, p. 246 - 252 (1993)
A series of ester prodrugs of propranolol was synthesized by incorporating substituents (straight: alkyl, branched alkyl, acyloxyalkyl and cycloalkyl) into the β-hydroxy function of propranolol with the aim of protecting the drug against first-pass metabolism following oral administration. The in-vitro hydrolysis rates of the prodrugs were, in increasing order, liver homogenate >> plasma > buffers. The pH-rate profile the prodrugs showed maximum stability around pH 4.0; the hydrolysis rates were drastically increased over pH 6.8. QSAR analysis revealed hydrophobic (π) and electronic (σ) effects of the substituents play the main roles for prodrug hydrolysis in buffers and plasma, while hydrolysis in liver homogenate could not be well explained by any of these parameters. Four prodrugs (O-acetyl-, O-butyryl-, O-isovaleryl- and O-cyclopropanoyl-propranolol) were selected for oral administration based on their hydrolysis in-vitro. Following oral administration of prodrugs to beagle dogs the absolute bioavailabilities (F) of propranol were about 2-4 fold that after an equivalent dose of propranolol. The prodrugs were rapidly absorbed and regenerated propranolol to attain peak plasma levels at 0-0.5 h. Intact prodrug levels were also observe which varied depending on their respective stabilities in in-vitro media. A linear relationship between F propranolol and log P was obtained. F further appeared to be parabolically dependent on the observed hydrolysis rates of prodrugs in liver homogenate suggesting optimal design manipulation. The overall in-vitro and in-vivo results showed that lipophilic prodrugs having higher chemical and enzymatic stability buffers and plasma, but susceptible to hydrolysis in the liver homogenate, to be the most promising prodrugs for improving oral bioavailability of propranolol.
Tritiation of DL propranolol with very high specific activity
Buchman,Pri Bar,Hagag
, p. 519 - 521 (1974)
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Synthetic method of propranolol hydrochloride
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Paragraph 0015; 0019; 0021; 0023-0025; 0027-0034; 0036; ..., (2021/09/04)
The invention belongs to the field of medicines, and particularly relates to a synthetic method of propranolol hydrochloride. The preparation method comprises the following steps: by taking epoxy chloropropane and methyl naphthol as raw materials and acetonitrile as a solvent, firstly reacting in tetramethylammonium hydroxide to obtain an intermediate product, then reacting the intermediate product with isopropylamine in the presence of a metal salt Ni/alpha-Al2O3 catalyst to obtain propranolol, and finally salinizing to obtain the propranolol hydrochloride. The method can significantly improve the yield and purity of the propranolol hydrochloride.
Preparation of a novel hydroxypropyl-γ-cyclodextrin functionalized monolith for separation of chiral drugs in capillary electrochromatography
Deng, Miaoduo,Xue, Mengyao,Liu, Yanru,Zhao, Min
, p. 188 - 195 (2021/02/26)
In this study, a novel hydroxypropyl-γ-cyclodextrin (HP-γ-CD) functionalized monolithic capillary column was prepared by one-pot sequential strategy and used for chiral separation in capillary electrochromatography for the first time. In one pot, GMA-HP-γ-CD as functional monomer was allowed to be formed via the ring opening reaction between HP-γ-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and then copolymerized directly with ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) in the presence of porogenic solvents via thermally initiated free radical polymerization. The preparation conditions of monoliths were optimized. Enantiomer separations of six chiral drugs including pindolol, clorprenaline, tulobuterol, clenbuterol, propranolol, and tropicamide were achieved on the monolith. Among them, pindolol, clorprenaline, and tropicamide were baseline separated with resolution values of 1.62, 1.73, and 1.55, respectively. The mechanism of enantiomer separation was discussed by comparison of the HP-γ-CD and HP-β-CD functionalized monoliths.
Synthesis method of beta-amino alcohol compounds
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Paragraph 0142-0160, (2020/03/29)
The invention discloses a synthesis method of beta-amino alcohol compounds. A carboxylic acid is adopted as a catalyst to promote amination of an epoxide to generate the beta-amino alcohol compounds.Compared with reported methods, this method has advantages of no use of metal catalysts, mild reaction conditions, the safe, non-toxic, cheap and readily available catalyst, a high product yield and high regioselectivity. In addition, a low-boiling-point carboxylic acid can be selected as the catalyst. When the low-boiling-point catalyst is used, excess raw materials and the catalyst can be recycled and reused, almost no waste is discharged to the environment, a post-treatment process does not require extraction, drying, filtration or the like, and a mixture after the reaction is finished is simply distilled or distilled under reduced pressure to obtain a crude product with higher purity. The synthesis process is simple, efficient, and environmentally friendly.