- Selenium-containing compounds and their use in treatment of neuro-degenerative diseases
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The present invention relates to compounds of Formula I or pharmaceutically acceptable salts, solvates or pro-drugs thereof. The invention also relates to a preparation method of the compound or the pharmaceutically acceptable salt, solvate or prodrug thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt, solvate or prodrug thereof and application ofthe compound or the pharmaceutically acceptable salt, solvate or prodrug thereof in preparation of drugs. The drugs are used for treating neuro-degenerative diseases.
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Paragraph 0089; 0097-0099
(2020/12/30)
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- Preparation method of 5- flucytosine
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The invention belongs to the technical field of chemical synthesis of medicines and relates to a preparation method of 5-flucytosine. The preparation method comprises the following steps: utilizing ethyl formate and methyl chloroformate to synthesize 2-chloro-3-oxo methyl propionate, then utilizing oxymethylisourea to close rings to obtain pyrimidine rings, utilizing potassium fluoride to substitute chlorine on the pyrimidine rings, utilizing phosphorus oxytrichloride to substitute hydroxyl groups on the pyrimidine rings, then adding ammonia water to lead chloride to be substituted with aminogroups, and hydrolyzing under an acid condition to obtain a product, namely the 5-flucytosine. The preparation method has the beneficial effects that the methyl chloroacetate is adopted for substituting methyl fluoroacetate to be used as a synthetic raw material of the 5-flucytosine, so that the use of highly-toxic chemicals such as the methyl fluoroacetate is avoided; simultaneously, since the price of the methyl chloroacetate is much lower than the price of the methyl fluoroacetate, the production cost can be saved; by utilization of the synthetic route provided by the invention, the higher-purity 5-flucytosine can be prepared without need of complex aftertreatment steps; simultaneously, the preparation method has higher overall yield and obvious industrial value and is worthy of being promoted and used on a large scale.
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Paragraph 0029-0031; 0037-0039; 0045-0047; 0053-0055
(2019/12/25)
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- A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate
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The biosynthesis of nitriles is known to occur through specialized pathways involving multiple enzymes; however, in bacterial and archeal biosynthesis of 7-deazapurines, a single enzyme, ToyM, catalyzes the conversion of the carboxylic acid containing 7-carboxy-7-deazaguanine (CDG) into its corresponding nitrile, 7-cyano-7-deazaguanine (preQ0). The mechanism of this unusual direct transformation was shown to proceed via the adenylation of CDG, which activates it to form the newly discovered amide intermediate 7-amido-7-deazaguanine (ADG). This is subsequently dehydrated to form the nitrile in a process that consumes a second equivalent of ATP. The authentic amide intermediate is shown to be chemically and kinetically competent. The ability of ToyM to activate two different substrates, an acid and an amide, accounts for this unprecedented one-enzyme catalysis of nitrile synthesis, and the differential rates of these two half reactions suggest that this catalytic ability is derived from an amide synthetase that gained a new function. Double duty: In bacterial and archeal biosynthesis of 7-deazpurines, a single enzyme, ToyM, catalyzes the two-step conversion of the carboxylic acid 7- carboxy-7-deazaguanine (CDG) into the corresponding nitrile, 7-cyano-7-deazaguanine (preQ0). The mechanism of this unusual direct transformation proceeds via the adenylation of CDG. This activates it to form the amide intermediate 7-amido-7-deazaguanine (ADG), which is in turn activated to form the nitrile.
- Nelp, Micah T.,Bandarian, Vahe
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supporting information
p. 10627 - 10629
(2015/09/02)
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- Inhibitors of histone deacetylase
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Disclosed are compounds which inhibit histone deacetylase (HDAC) enzymatic activity. Also disclosed are pharmaceutical compositions comprising such compounds as well as methods to treat conditions, particularly proliferative conditions, mediated at least
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- Inhibitors of histone deacetylase
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Disclosed are compounds which inhibit histone deacetylase (HDAC) enzymatic activity. Also disclosed are pharmaceutical compositions comprising such compounds as well as methods to treat conditions, particularly proliferative conditions, mediated at least in part by HDAC.
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Page/Page column 46
(2010/02/14)
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- BROADSPECTRUM SUBSTITUTED BENZISOXAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
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The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs esters and metabolites thereof.It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.
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Page/Page column 26
(2008/06/13)
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- Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines
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Classical and nonclassical isosteric C8-N9 bridged analogues of the multitargeted antifolate LY231514 were synthesized as inhibitors of thymidylate synthase (TS), dihydrofolate reductase (DHFR), and as antitumor and antiopportunistic infection agents. The
- Gangjee,Vidwans,Elzein,McGuire,Queener,Kisliuk
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p. 1993 - 2003
(2007/10/03)
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- The alkaline hydrolysis of aryl (2E)-3-(4′-hydroxyphenylazo)propenoates. A kinetic study
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The alkaline hydrolysis of the title esters, possessing three conjugated π units between the internal nucleophile (the hydroxyl group) and the reaction center, follows an E1cB mechanism involving the participation of an "extra extended" p-oxo azoketene type intermediate. For the hydrolysis of the 2,4-dinitrophenyl ester kinetic data, activation parameters and trapping of the intermediate are consistent with a dissociative pathway carrying the reaction flux. The effect of the leaving group variation on reactivity agrees with the proposed mechanism, and the existence of an intermediate is also supported by diode array stopped-flow experiments. The presence of sp2 nitrogen atoms in the conjugated backbone is beneficial to the dissociative mechanism.
- Cevasco,Vigo,Thea
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p. 7685 - 7690
(2007/10/03)
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