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.
Solution and mixing thermodynamics of propranolol and atenolol in aqueous media
Triana, Maria T.,Reyes, Andrea C.,Jimenez-Kairuz, Alvaro F.,Manzo, Ruben H.,Martinez, Fleming
, p. 73 - 81 (2009)
Based on the van't Hoff and Gibbs equations, the thermodynamic functions Gibbs energy, enthalpy, and entropy of dissolution, and of mixing of propranolol (PPN) and atenolol (ATN) in water at pH=11.5, were evaluated from solubility values determined at sev
Synthetic method of propranolol hydrochloride
-
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.
Synthesis and application of Cu(II) immobilized MCM-41 based solid Lewis acid catalyst for aminolysis reaction under solvent-free condition
Chaudhary, Garima,Gupta, Neha,Singh, Amit Pratap
, (2021/07/22)
In this paper, a Cu(II) immobilized periodic mesoporous organosilica (PMOs) was synthesized and used as a reusable solid Lewis acid catalyst for the aminolysis of epoxides under solvent-free conditions. An amide-based ligand, L-propylsilyl (1) having a specific binding pocket was prepared and fabricated on mesoporous MCM-41 to produce mesoporous organosilica L-propylsilyl@MCM-41 (2). Further, it has been utilized for anchoring Cu(II) ions under controlled reaction conditions to yield solid Lewis acid catalyst Cu(II)-L-propylsilyl@MCM-41 (3). The synthesized catalyst 3 exhibits significantly higher catalytic activity for aminolysis compared to hitherto known solid Lewis acid catalysts. An extensive range of β-amino alcohols with high regio and stereoselectivity were prepared by using catalyst 3. The catalyst was recovered easily and reused eight times without any loss in its catalytic activity. Furthermore, the synthesis of clinically significant propranolol (β-blocker) from α- naphthyl glycidyl ether was attained successfully using catalyst 3 in a very decent yield.
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.
Preparation method of propranolol
-
Paragraph 0018-0020, (2021/06/23)
The invention discloses a preparation method of propranolol. The method comprises the following preparation steps: taking naphthol, epichlorohydrin and isopropylamine as initial raw materials, adding a phase transfer catalyst and a reaction solvent, and reacting under the action of alkali to generate propranolol. The process route and post-treatment steps of the route are greatly simplified, the reaction conditions are not harsh and are easy to control, and industrial production can be realized; and the raw materials adopted by the route are easy to obtain on the market, and the price is relatively low, so that the cost is saved.
Synthesis method of beta-amino alcohol compounds
-
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.
Synthetic method of propranolol hydrochloride (by machine translation)
-
Paragraph 0030-0033, (2020/06/30)
To the method, methylnaphthol and epichlorohydrin are subjected to etherification reaction under the action of an alkali condition and a phase transfer catalyst to obtain the key intermediate 3 - (1 - naphthyloxy) -1, 2 - epoxypropane, and then refined to obtain the propranolol hydrochloride crude product which has the advantages of short synthetic route, simple operation and suitableness for industrial production 99.8%. (by machine translation)
Facile Synthesis of Propranolol and Novel Derivatives
Bach, Long Giang,Le, Van Thuan,Nguyen, Tan Tai,Nguyen, Thi Anh Nga,Nguyen, Thi Thuong,Nguyen, Trinh Duy,Tran, Nguyen Hai Tai,Tran, Vy Anh,Vo, The Ky,Vo, Thu-Thao Thi
, (2020/10/02)
Propranolol is one of the first medications of the beta-blocker used for antihypertensive drugs. This study reports the facile route for the synthesis of propranolol and its novel derivatives. Herein, propranolol synthesis proceeded from 1-naphthol and isopropylamine under mild and less toxic conditions. Novel propranolol derivatives were designed by reactions of propranolol with benzoyl chloride, pyridinium chlorochromate, and n-butyl bromide through esterification, oxidation reduction, and alkylation, respectively. The isolation and purity of compounds were conducted using column chromatography and thin-layer chromatography. Mass spectrometry and 1H-NMR spectroscopy were applied to identify new compounds structure. Propranolol derivatives from 2-chlorobenzoyl chloride (compound 3), 2-fluorobenzoyl chloride (compound 5), and especially acetic anhydride (compound 6) manifested high yields and significantly increased water solubility. Six semisynthetic propranolol derivatives promise to improve antioxidative and biological activities.
Preparation and evaluation of a triazole-bridged bis(β-cyclodextrin)–bonded chiral stationary phase for HPLC
Shuang, Yazhou,Liao, Yuqin,Wang, Hui,Wang, Yuanxing,Li, Laisheng
, p. 168 - 184 (2019/11/25)
A triazole-bridged bis(β-cyclodextrin) was synthesized via a high-yield Click Chemistry reaction between 6-azido-β-cyclodextrin and 6-propynylamino-β-cyclodextrin, and then it was bonded onto ordered silica gel SBA-15 to obtain a novel triazole-bridged bis (β-cyclodextrin)–bonded chiral stationary phase (TBCDP). The structures of the bridged cyclodextrin and TBCDP were characterized by the infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis. The chiral performance of TBCDP was evaluated by using chiral pesticides and drugs as probes including triazoles, flavanones, dansyl amino acids and β-blockers. Some effects of the composition in mobile phase and pH value on the enantioseparations were investigated in different modes. The nine triazoles, eight flavanones, and eight dansyl amino acids were successfully resolved on TBCDP under the reversed phase with the resolutions of hexaconazole, 2′-hydroxyflavanone, and dansyl-DL-tyrosine, which were 2.49, 5.40, and 3.25 within 30 minutes, respectively. The ten β-blockers were also separated under the polar organic mode with the resolution of arotinolol reached 1.71. Some related separation mechanisms were discussed preliminary. Compared with the native cyclodextrin stationary phase (CDSP), TBCDP has higher enantioselectivity to separate more analytes, which benefited from the synergistic inclusion ability of the two adjacent cavities and bridging linker of TBCDP, thereby enabling it a promising prospect in chiral drugs and food analysis.
