- Synthesis of novel 3-[(2R*)-2-[(2S*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]-urea/thiourea derivatives and evaluation of their antimicrobial activities
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A new series of biologically active 3-[(2R*)-2-[(2S*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]-urea/thiourea derivatives (1) have been designed and synthesized in four steps from 6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene (2). The structures of newly synthesized compounds (1a–j) were confirmed by 1H, 13C NMR, and HRMS. The major advantages of the present article include the development of an efficient eluent system for good separation of diastereomers (2a and 2b) with high yields and synthesis of (R*)-2-(benzylamino)-1-((S*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol (3) in high yields (87%) from epoxide (2a) through new reaction conditions. The synthesized compounds (1a–j) exhibited moderate to excellent antimicrobial activities against both bacterial strains (gram + Ve and gram –Ve strains) and fungal strains. Among the tested compounds, promising lead compounds were identified (compounds 1a and 1d against bacterial strains and compound 1h and 1j against fungal strains) and their antimicrobial activities are comparable with the reference standard.
- Mannam, Madhava Rao,Srimurugan,Kumar, Pramod,Chamarthi, Naga Raju,Prasad
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supporting information
p. 65 - 74
(2019/07/15)
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- 2-amino-1 - (- 6-fluoro-2- chromanyl ) ethanol synthesis method
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The invention provides a synthesis method of 2-amino-1-(-6-fluoro-2-chromanyl)ethanol, which comprises the following steps: synthesizing 6-fluorochromanyl-2-carboxylic acid (I) used as an initial raw material into 6-fluorochromanyl-2-formacylimidazole (II); synthesizing the obtained 6-fluorochromanyl-2-formacylimidazole (II) into 1-(6-fluoro-2-chromanyl)-2-nitro-1-ethyl ketone (III); and finally, reducing the obtained 1-(6-fluoro-2-chromanyl)-2-nitro-1-ethyl ketone (III) into 2-amino-1-(-6-fluoro-2-chromanyl)ethanol (IV). The method provided by the invention has the advantages of accessible raw materials and mild reaction conditions, and is simple to operate and more suitable for industrial production.
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Paragraph 0054-0055; 0057; 0059
(2016/10/09)
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- PREPARATION OF NEBIVOLOL
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Processes for the synthesis of pharmacologically active 2,2-iminobisethanol derivatives, e.g., 2H-1-benzopyran-2 methanol-α,α′-iminobis(methylene)]bis-[6-fluoro-3,4-dihydro-[2R*[R*[R*(S*)]]]], and their pharmaceutically acceptable salts.
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Page/Page column 13
(2011/10/19)
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- Process for the Production of Nebivolol
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The subject of the invention is a process for the production of the racemic active ingredient nebivolol, in which diastereomeric cyanohydrins are produced, separated, and the separated diastereomers are coupled to one another after a transformation, preferably a partial or complete reduction of the cyano group or a Pinner saponification.
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Page/Page column 4-5
(2008/12/08)
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- PROCESS FOR PREPARING NEBIVOLOL
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The present invention relates to a process for preparing Nebivolol and, more particularly, to an improved process for synthesizing enantiomerically enriched 6-fluoro chroman alcohol or epoxide derivatives of formula, wherein R and X is defined in the description; as useful intermediates in the preparation of Nebivolol.
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Page/Page column 26
(2008/12/06)
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- Synthesis of (S,R,R,R)-α,α′-iminobis(methylene)bis(6- fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol)
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The β1-adrenergic antagonist (S,R,R,R)-α, α′-iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2- methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed. Georg Thieme Verlag Stuttgart.
- Wang, Nai-Xing,Yu, An-Guang,Wang, Gui-Xia,Zhang, Xiu-Hui,Li, Qian-Shu,Li, Zhen
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p. 1154 - 1158
(2008/02/02)
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- Hydroxylated nebivolol metabolites
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Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.
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- Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-Nebivolol
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The total synthesis of (S,R,R,R)-Nebivolol, a hypertensive agent, is reported. Claisen rearrangement and a one-pot Sharpless asymmetric epoxidation, intramolecular epoxide opening with internal phenoxide anion to generate the chiral chromane are the key s
- Chandrasekhar,Venkat Reddy
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p. 6339 - 6344
(2007/10/03)
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