- CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUATERNARY AMMONIUM SALT STRUCTURE
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The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β2-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma.
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Paragraph 0140
(2019/11/11)
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- Synthesis, pharmacological activity, and chromatographic enantioseparation of new heterocyclic compounds of the aryloxyaminopropanol type derived from 4-hydroxyphenylalkanones
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Abstract: In the paper, a series of six pharmacologically active compounds (β-adrenolytics) derived from 4-hydroxyphenylethanone and 4-hydroxyphenylpropan-1-one are reported. The compounds incorporate pyrrolidin-1-yl and 4-methylpiperazin-1-yl substituent
- ?i?máriková, Ru?ena,Némethy, Andrej,Habala, Ladislav,Ra?anská, Eva,Valentová, Jindra,Hroboňová, Katarína
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p. 969 - 976
(2018/05/07)
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- Synthesis and Biological Evaluation of New Combined α/β-Adrenergic Blockers
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The synthesis, characterization, and pharmacological evaluation of new aryloxyaminopropanol compounds based on substituted (4-hydroxyphenyl)ethanone with alterations in the alkoxymethyl side chain in position 2 and with 2-methoxyphenylpiperazine in the ba
- Némethy, Andrej,Vavrinec, Peter,Vavrincová-Yaghi, Diana,?epcová, Diana,Mi?úth, Svetozár,Král'ová, Eva,?i?máriková, Ru?ena,Ra?anská, Eva
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- A 5-substituted phenylpropyl furan-2-carboxylic acid and its derivative synthesis method
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The invention discloses a synthesis method for 5-substituted benzofuran-2-carboxylic acid and the derivatives thereof. The synthesis method comprises the following steps of: 1) performing a chloromethylation reaction or a bromomethylation reaction on 4-substituted phenol to generate 2-halogenated methyl-4-substituted phenol; 2) reacting 2-halogenated methyl-4-substituted phenol with triphenylphosphine to generate 2-hydroxyl-5-substituted halogenated benzyltriphenyl phosphonium; 3) performing a ring-closing reaction on 2-hydroxyl-5-substituted halogenated benzyltriphenyl phosphonium and trichloroacetyl chloride in an alkaline condition to obtain 2-trichloromethyl-5-substituted benzofuran; and 4) performing alcoholysis on 2-trichloromethyl-5-substituted benzofuran in an acidic condition to obtain 5-substituted benzofuran-2-carboxylic ester, and then performing functional group conversion to obtain a series of derivatives. According to the synthesis method provided by the invention, cheap and easily-available raw materials are used, thus reducing production cost; and moreover, the synthesis method is simple and convenient in process, easy to enlarge, and high in implement value.
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Paragraph 0031; 0032
(2016/11/21)
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- 5-(1-Acetoxyvinyl)-cyclosaligenyl-2′,3′-dideoxy-2′, 3′- didehydrothymidine monophosphates, a second type of new, enzymatically activated cyclosaligenyl pronucleotides
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In our attempt to further develop the cycloSal pronucleotide concept, we report on 5-(1-acetoxyvinyl)-cycloSal-d4TMPs as a new type of enzyme-activated pronucleotides. These compounds were converted into 5-acetyl-cycloSal-d4TMPs by (carboxy)esterase cleav
- Gisch, Nicolas,Pertenbreiter, Florian,Balzarini, Jan,Meier, Chris
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supporting information; experimental part
p. 8115 - 8123
(2009/12/07)
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- A water based method for hydroxymethylation of phenols and phenolic ketones
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A water based eco-friendly method for the hydroxymethylation of phenols and phenolic ketones has in good yield been developed.
- Goswami, Jonali,Borthakur, Naleen,Goswami, Amrit
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p. 200 - 203
(2007/10/03)
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- The practical synthesis of a uterine relaxant, Bis( 2-{[(2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl) -phenyl]ethyl}amino) -1,2,3,4-tetrahydronaphthalen-7-yl]oxy}-N,N-dimethylacetamide) sulfate (KUR-1246)
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The synthetic route for a uterine relaxant, bis(2-{[ (2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3- (2-hydroxyethyl)-phenyl]ethyl}amino) -1,2,3,4-tetrahydronaphthalen-7-y1]oxy}-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.
- Yanagi, Takashi,Kikuchi, Ken,Takeuchi, Hideki,Ishikawa, Takehiro,Nishimura, Toshihiro,Yamamoto, Iwao
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p. 1018 - 1023
(2007/10/03)
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The intramolecular condensation of o-acyloxybenzylidenetriphenylphosphoranes leads to acylated products in t-BuOH and to benzofurans in toluene. Mechanistic aspects are discussed. A general method is described for the synthesis of benzofurans from o-cresols, o-hydroxybenzylic alcohols, and deactivated phenols.
- Hercouet,Le Corre
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p. 2867 - 2873
(2007/10/02)
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- α-Aminoalkyl-4-hydroxy-3-alkylsulfonylmethylbenzyl alcohols having β-adrenergic stimulant activity
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α-Aminoalkyl-4-hydroxy-3-alkylsulfonylmethylbenzyl alcohols having β-adrenergic stimulant activity, particularly as selected bronchodilators, are prepared from 4-hydroxyphenones by conversion to a 3-alkylsulfonylmethylphenone, bromination of these phenones and treatment of the resulting α-bromo derivatives with an N-benzyl secondary amine, followed by catalytic hydrogenation to remove the benzyl groups and reduce the ketone moiety.
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- N,N'-BIS[2-3-SUBSTITUTED-4-HYDROXYPHENYL)-2-HYDROXYETHYL)]-POLYMETHYLENEDIAMINES
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N,N'-Bis 2-(3-substituted-4-hydroxyphenyl)-ethyl or-2-hydroxyethyl!-polymethylenediamines having β-adrenergic stimulant activity particularly as selective bronchodilators, are prepared generally by condensation of an N-benzylphenethylamine with a polymethylene dihalide or by reaction of an α-bromoacetophenone with an N,N'-dibenzyl-polymethylenediamine, with further operations depending on the nature of the 3-substituent, and subsequently hydrogenating catalytically with for example palladium-on-carbon. The key intermediates are also part of the invention.
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- 4-HYDROXY-ALPHA-[(3,4-METHYLENEDIOXYPHENYL)ISOPROPYLAMINOETHYL]-3-(METHYLSULFONYLMETHYL)BENZYL ALCOHOL
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4-Hydroxy-α-(3,4-methylenedioxyphenyl) isopropylaminomethyl!-3-(methylsulfonylmethyl)ben zyl alcohol having β-adrenergic stimulant activity, particularly as a selective bronchodilator, is prepared from 4-hydroxyacetophenone by conversion to 3-methylsulfonylmethylacetophenone, bromination and conversion of this phenone to the phenylglyoxal and treatment of the resulting glyoxal derivative with 3,4-methylenedioxyphenylisopropylamine followed by simultaneous reduction of the imine and ketone moieties and catalytic hydrogenation to remove the benzyl group.
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