- A new synthesis of Entacapone and report on related studies
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A new synthesis of the catechol-O-methyltransferase (COMT) inhibitor, entacapone (E-isomer) has been achieved under mild conditions by amine-mediated demethylation of the precursor 2-Cyano-3-(3- hydroxy-4-methoxy-5-nitrophenyl) prop-2-eneamide, wherein the methoxyl group adjacent to a nitro group gets demethylated under nucleophilic attack. Similar demethylation was achieved on ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate, 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethylprop-2-enamide, ethyl 2-cyano-3-(3-hydroxy-4-methoxy-5-nitrophenyl) prop-2-enoate and ethyl 2-cyano-3-(4-methoxy-3-nitrophenyl) prop-2-enoate. The scope of demethylation has been studied. Analogues of ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate wherein a methoxyl group is not adjacent to a NO 2 group are unaffected and phenolic derivatives yield the amine salts. Entacapone has been converted to salts with organic bases. The crystal structure of the isomer of entacapone (Z-isomer), a significant human metabolite of E-isomer has been established. NMR methods for deriving E and Z geometry and other similar molecules have been successfully established, mainly by studying the proton coupled 13C spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue. [Figure not available: see fulltext.]
- Harisha, Attimogae Shivamurthy,Nayak, Suresh Parameshwar,Pavan,Shridhara,Sundarraja Rao,Rajendra,Pari, Koteppa,Sivaramkrishnan,Guru Row,Nagarajan, Kuppuswamy
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p. 1977 - 1991
(2015/12/30)
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- Novel triethylamine mediated thermal reactions of 3-aryl-2-cyanoprop-2-enoic acid derivatives - Demethylation, reduction and vinylogation
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3-Aryl-2-propenoic acid derivatives undergo interesting reactions with hot triethylamine. Substrates like 6 having a methoxyl with a nitro in the ortho and cyanoacrylic derivatives in the para positions give O-demethylated products, for example, entacapone 7. On the other hand compounds like 16 having the NO2 in the para and cyanoacrylic in the ortho position undergo reduction and vinylogation. The latter phenomenon is observed in the absence of the NO2 group also.
- Harisha, Attimogae Shivamurthy,Nayak, Suresh Parameshwar,Nagarajan, Kuppuswamy,Guru Row, Tayur Narasingarow,Hosamani, Amar A.
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supporting information
p. 1427 - 1431
(2015/03/04)
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- DENGUE AND WEST NILE VIRUS PROTEASE INHIBITORS
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Compounds and methods of treating or preventing a Flavivirus infection in a subject are provided. The methods comprise administering to the subject a therapeutically effective amount of a compound as described herein. The methods are useful in treating and/or preventing Flavivirus infections such as, for example, West Nile Virus, Dengue Virus, and Japanese Encephalitis Virus. Methods of inhibiting a Flavivirus protease in a cell are also provided.
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Page/Page column 28; 29
(2014/10/18)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ENTACAPONE
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The invention relates to Novel Z form of ENTACAPONE-( Z N1N- Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-acrylamide . This invention also relates to a process for the preparation of Novel Z form of ENTACAPONE- by treating pure 3- O- alkylated Entacapone with aluminium chloride and pyridine with dichloromethane as solvent to get crude Entacapone with no impurity and dissolving the crude entacapone in one or more solvents selected from soluble or partially soluble solvents or their mixtures filtering . and concentrating by distillation
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Page/Page column 14-15
(2008/06/13)
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