- Synthesis method of 4-chloro-2-methylthiopyrimidine
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The invention belongs to the technical field of organic synthesis, in particular to a synthesis method of 4-chloro-2-methylthiopyrimidine. The method includes taking 2-thiouracil as a raw material, dimethyl sulfate as a methylation reagent, thionyl chloride and phosphorus oxychloride as a chlorination reagent, and synthesizing the 4-chloro-2-methylthiopyrimidine through methylation and chlorination.The dimethyl sulfate is taken as the methylation reagent to replace methyl bromide or methyl iodide, and thus the safety of the reaction is increased, and the cost is decreased; sodium hydroxide istaken as alkali to replace sodium methoxide or butyl lithium, and thus the safety of the reaction is increased, and the cost is reduced; toluene is taken as a reaction solvent, and thus the dosage ofthe chlorinated reagent is greatly reduced, the reaction safety is greatly improved, the cost is reduced, and the post-treatment operation is simplified; and the sulfoxide chloride and the phosphorusoxychloride are taken as the mixed chlorinating reagent, and thus the reaction yield is greatly improved.
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Paragraph 0022; 0023; 0024; 0025-0028; 0037-009
(2019/06/30)
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- NOVEL IN-VIVO PROBE FOR REAL TIME LONGITUDINAL MONITORING OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN LIVING CELLS AND ANIMALS
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The present disclosure relates to an in vivo fluorescent or radioactive probe represented by a compound of formula I which is capable of longitudinal imaging of inducible nitric oxide synthase (iNOS) expression in living cells and living animals on a real time basis. The probe of the present disclosure can exhibit specific and high affinity binding to the iNOS enzyme with reduced enzyme inhibitory property and also enables longitudinal monitoring of iNOS expression along with its activity or NO production in a same experimental subject throughout the progression of a physiological or disease process without employing separate subjects as controls and experimental. The present disclosure further provides a rapid and inexpensive real time method for visualizing iNOS expression and its activity in living cells and living animals precisely, conveniently and reversibly along with simultaneous in vivo imaging of its catalytic product, nitric oxide (NO) in live physiological settings.
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Paragraph 0074
(2018/06/06)
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- HETEROCYCLYL PYRIMIDINE ANALOGUES AS TYK2 INHIBITORS
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The present invention relates to compounds of formula (I), wherein R, R1, X1 to X5 have the meaning as cited in the description and the claims. Said compounds are useful as TYK2 inhibitors for the treatment or prophylaxis
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Page/Page column 64
(2014/01/07)
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- NOVEL PHENYL(4-PHENYLPYRIMIDIN-2-YL)AMINE DERIVATIVES, THEIR PREPARATION, AS MEDICAMENTS, PHARMACEUTICAL COMPOSITIONS AND IN PARTICULAR AS IKK INHIBITORS
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The disclosure relates to a compound of formula (I): wherein R, R2, R3, R4, R5, Z, W and D are as defined in the specification, to compositions containing them, to processes for preparing them, and to their use in the treatment or prevention of conditions
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Page/Page column 20
(2010/04/23)
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- 2-ANILINO-4-HETEROARYL PYRIMIDINE DERIVATIVES, AND PREPARATION THEREOF AS MEDICAMENTS, PHARMACEUTICAL COMPOSITIONS, AND IN PARTICULAR IKK INHIBITORS
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The disclosure relates to a compound of formula (I): wherein R, R2, R3, R4, R5, z, D and W are as defined in the specification, to compositions containing them, to processes for preparing them, and to their use in the treatment or prevention of conditions capable of being modulated by the inhibition of the activity of protein kinases.
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Page/Page column 20-21
(2010/05/13)
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- Novel 2,4-Dianilinopyrimidine Derivatives, the Preparation Thereof, Their Use as Medicaments, Pharmaceutical Compositions and, in Particular, as IKK Inhibitors
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The disclosure relates to compounds of formula (I): wherein R1-R5, A and Y are as defined in the disclosure, to compositions comprising said compounds, and to processes for making and methods of using the same.
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Page/Page column 67
(2008/12/04)
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- Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors
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By the screening of a combinatorial library for inhibitors of nitric oxide (NO) formation by the inducible isoform of nitric oxide synthase (iNOS) using a whole-cell assay, 2-(imidazol-1-yl)pyrimidines were identified. Compounds were found to inhibit the dimerization of iNOS monomers, thus preventing the formation of the dimeric, active form of the enzyme. Optimization led to the selection of the potent, selective, and orally available iNOS dimerization inhibitor, 21b, which significantly ameliorated adjuvant-induced arthritis in a rat model. Analysis of the crystal structure of the 21b-iNOS monomer complex provided a rationalization for both the SAR and the mechanism by which 21b blocks the formation of the protein-protein interaction present in the dimeric form of iNOS.
- Davey, David D.,Adler, Marc,Arnaiz, Damian,Eagen, Keith,Erickson, Shawn,Guilford, William,Kenrick, Margaret,Morrissey, Michael M.,Ohlmeyer, Mike,Pan, Gonghua,Paradkar, Vidyadhar M.,Parkinson, John,Polokoff, Mark,Saionz, Kurt,Santos, Cecile,Subramanyam, Babu,Vergona, Ron,Wei, Robert G.,Whitlow, Marc,Ye, Bin,Zhao, Zuchun,Devlin, James J.,Phillips, Gary
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p. 1146 - 1157
(2007/10/03)
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- Synthesis and biological evaluation of new pyrimidine derivatives
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4-Oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine (2-thiouracil) 1 is reacted with a series of diazotized aromatic amines to give compounds 2a-f. On the other hand compound 1 is s-methylated by methyl iodide giving 4-oxo-2-methylthioxo 1,2,3,4-tetrahydropyrimid
- Fathalla,Radwan,Awad,Mohamed
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p. 980 - 985
(2007/10/03)
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- Tautomerism and infrared spectra of thiouracils. Matrix isolation and ab initio studies
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A study of the infrared (IR) spectra of a variety of thiouracils isolated in low-temperature inert matrices demonstrated that 2- and 4-thiouracils together with their N1- and N3-methylated derivatives as well as 2,4-dithiouracil exist under these conditions only in the oxothione or dithione tautomeric forms. In contrast, S2- and S4-methylated derivatives under the same conditions exist as a mixture of hydroxy and oxo tautomeric forms. The ratio of concentrations of the tautomers K(o/h) = ([oxo]/[hydroxy]) and the free energy differences, ΔG, were experimentally estimated from the ratio of the absorbances of the NH and OH stretches. The values obtained are K(o/h) = 1.5 and ΔG = -1.7 kJ/mol for 2-(methylthio)uracil and K(o/h) = 0.5 and ΔG = +2.5 kJ/mol for 4-(methylthio)-6-methyluracil. An assignment of the observed infrared bands, particularly those related to the C=S stretching vibrations, is proposed on the basis of the comparison of the matrix spectra from different derivatives and of the spectra calculated by using ab initio methods (3-21G* basis set).
- Rostkowska,Szczepaniak,Nowak,Leszczynski,KuBulat,Person
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p. 2147 - 2160
(2007/10/02)
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