- Continuous flow synthesis of some 6- And 1,6-substituted 3-cyano-4-methyl-2-pyridones
-
In this study, six 6- and 1,6-substituted-3-cyano-4-methyl-2-pyri-dones were synthesized in a continuous flow microreactor system. The syntheses were realized at room temperature and the obtained results were compared to those achieved within classical syntheses. In order to optimize the continuous flow syntheses and increase the yield of the products, the retention time in the microreactor was varied by changing the flow rates of the reactant solutions. Furthermore, the reaction was optimized for 3-cyano-4,6-dimethyl-2-pyridone and 3-cyano-6-hydroxy-4-methyl-2-pyridone, which are comercially important in the pharmaceutical and dye industries. Both 2-pyridones were obtained in satisfactory yield of circa 60 % in less than 10 min. The resulting compounds were characterized by their melting points, FT-IR, 1H-NMR and UV–Vis spectra. The efficiency of the presented method for the synthesis of 2-pyridone-based molecules has promising potential for industrial production.
- Tadi?, Julijana,Mihajlovi?, Marina,Jovanovi?, Mi?a,Mijin, Du?an
-
p. 531 - 538
(2019/08/30)
-
- Synthesis and thermal properties of arylazo pyridone dyes
-
Thermal degradation properties of 5-(4-substitutedphenylazo)-3-amido-6-hydroxy-4-methyl-2-pyridones and 5-(4-substitutedphenylazo)-3-cyano-6-hydroxy-4-methyl-2-pyridones dyes, differing in electron withdrawing and electron donating substituents in para-position of diazo components were examined. The structure of the synthesized compounds has been confirmed by 1H NMR,13C NMR, FTIR, UV–Vis and XRD analysis techniques. The results obtained with thermogravimetric analysis (TGA) – derivative thermogravimetry (DTG) and differential thermal analysis (DTA) were combined with GC-mass spectral fragmentation to obtain thermal decomposition mechanism. Non-isothermal kinetics were monitored by application of TGA-DTG-DTA. For Kinetic behavior of the investigated dyes during their degradation in an inert atmosphere, Kissinger, Ozawa, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) isoconversional (model-free) methods were applied. It was found that different thermal stabilities of investigated dyes are the consequence of their different chemical structures, including diverse substituents.
- Porobi?, Slavica J.,Krsti?, Aleksandar D.,Jovanovi?, Dragana J.,La?arevi?, Jelena M.,Katni?, ?urica B.,Mijin, Du?an ?.,Marinovi?-Cincovi?, Milena
-
-
- NEK6 KINASE INHIBITORS USEFUL FOR THE TREATMENT OF SOLID TUMORS
-
The mitotic kinases regulating the dynamics of centrosomes and the functions of the mitotic spindle are potential targets for the antitumour therapy. In the present invention some molecules with inhibitory activity on NEK6 have been identified. The present invention relates to such molecules and to the compositions including them for use as inhibitors of NEK6 in a method of treatment of tumours both in monotherapy and in combinations with other drugs.
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Page/Page column 14
(2019/10/29)
-
- Synthesis, solvatochromism, and biological activity of novel azo dyes bearing 2-pyridone and benzimidazole moieties
-
New azo dyes bearing 2-pyridone and benzimidazole moieties were prepared using diazotization of 4-(1H-benzo[d]imidazol-2-yl)aniline and coupling of the obtained diazonium salt with substituted 3-cyano-2-pyridones. Obtained compounds were characterized via UV-Vis, FT-IR, and 1 H and 13 C NMR spectroscopy as well as by elemental analysis data. The UV-Vis spectra of the synthesized dyes were measured in thirteen solvents of different properties at room temperature. Solvatochromism and tautomerism of novel azo dyes were discussed. An MTT (3,4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test was performed to prove the biocompatibility of the investigated dyes. The investigated dyes exhibited satisfying antiproliferative activities against both tumor cell lines, MDA-MB-231 and HCT-116, demonstrating the potent capacity for treatment of tumors.
- Mijin, Du?an,Bo?i? Nedeljkovi?, Biljana,Bo?i?, Bojan,Kovrlija, Ilijana,Ladarevi?, Jelena,U??umli?, Gordana
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p. 896 - 907
(2018/06/07)
-
- Preparation method for nevirapine intermediate
-
The invention provides a preparation method for a nevirapine intermediate. The preparation method comprises: performing a cyclization reaction of ammonia water, methyl cyanoacetate and methyl acetoacetate to form a compound hydroxyl: 2,6-dihydroxy-3-cyano-4-methylpyridine; adding triethylamine dropwise, introducing chlorine gas at the temperature until the reaction is complete, and obtaining 2,6-dichloro-3-cyano-4-methylpyridine; adding concentrated sulfuric acid, heating to 120 DEG C to react for 3-5 h, and then cooling to 60 DEG C; adding water to perform hydrolysis reaction, and obtaining 2,6-dichloro-3-amido-4-methylpyridine; adding a degradation reagent sodium hypochlorite, and obtaining a nevirapine intermediate 2,6-dichloro-3-amino-4- methylpyridine by Hofmann reaction. According tothe preparation method, commonly used phosphorus oxychloride is replaced with the directly introduced chlorine gas, which solves the problems that the wastewater content is too high, it is difficultto perform treatment and the odor of phosphorus oxychloride is bad, and the one-time yield of the product is 90.1%.
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Paragraph 0009; 0031; 0041; 0051; 0059-0061
(2019/01/14)
-
- Wnt SIGNALING INHIBITOR, COMPOSITION, AND COMPOUND AS USE THEREFOR
-
PROBLEM TO BE SOLVED: To provide an inhibitor for Wnt signaling route. SOLUTION: The present invention provides a compound represented by formula I, and a composition comprising the compound (X1-X8 independently represent CR4 or N; Y1 is H or C (R4)3; Y2 and Y3 independently represent H, halogen or C (R3)3; R1 and R2 independently represent H, halogen, C1-6 alkyl, quinolinyl or the like; R3s independently represent H, halogen, cyano, C1-6 alkyl or the like; R4s independently represent H, halogen, cyano, C1-6 alkoxy or the like). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0076; 0077
(2017/08/15)
-
- Inhibiting WNT signal conduction of compound, composition and use thereof (by machine translation)
-
The invention relates to a having the general formula (1) compounds and compositions thereof, and the use of the compound or composition thereof to inhibit WNT signal transmission method. The compounds of this invention and its composition can effectively inhibit the secretion of WNT protein, inhibit WNT signal conduction, so the WNT-mediated disease with a very good therapeutic effect. . (by machine translation)
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Paragraph 0171; 0174; 0175; 0176
(2017/12/27)
-
- TUMOR BIOMARKERS AND USE THEREOF
-
Disclosed herein are biomarkers related to WNT signal transduction pathway, as well as methods and kits comprising the same. Further, the present disclosure relates to the use of the biomarkers in patient selection, companion diagnostics, and treatment of cancer.
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Paragraph 0227-0228
(2016/12/22)
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- Compound as WNT Signaling Inhibitor, Composition, and Use Thereof
-
The present invention relates to a compound having the structure of Formula I as inhibitor of WNT signal transduction pathways, as well as a composition comprising the compound. Further, the present invention relates to the use of the compound and the method of inhibiting the WNT signal transduction pathways.
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Paragraph 0173; 0174
(2015/05/05)
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- AZAINDENOISOQUINOLINE TOPOISOMERASE I INHIBITORS
-
The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer.
- -
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Paragraph 0143
(2014/02/16)
-
- COMPOUNDS FOR TREATMENT OF FIBROSIS DISEASES
-
The present invention relates to compounds as inhibitor of WNT signal transduction pathway, as well as a composition comprising the same. Further, the present invention relates to the use of the compounds in the treatment of fibrosis. Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury.
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Paragraph 0158-0159
(2014/10/15)
-
- COMPOUNDS FOR TREATMENT OF CANCER
-
The present invention relates to compounds as inhibitor of WNT signal transduction pathway, as well as a composition comprising the same. Further, the present invention relates to the use of the compounds in the treatment of cancer.
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Paragraph 0172; 0173
(2014/10/18)
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- BICYCLIC INHIBITORS OF ALK
-
The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, Formula (1) wherein R1, R2, R3, X, Y, Z, A, B, G1, m, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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-
Paragraph 0306; 0362
(2014/06/25)
-
- Design of novel potent inhibitors of human uridine phosphorylase-1: Synthesis, inhibition studies, thermodynamics, and in vitro influence on 5-fluorouracil cytotoxicity
-
Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors of human uridine phosphorylase (hUP) have been proposed as a strategy to increase Urd levels. We describe synthesis and characterization of a new class of ligands that inhibit hUP type 1 (hUP1). The design of ligands was based on a possible SN1 catalytic mechanism and as mimics of the carbocation in the transition state of hUP1. The kinetic and thermodynamic profiles showed that the ligands here presented are the most potent in vitro hUP1 inhibitors developed to date. In addition, a lead compound improved the antiproliferative effects of 5-FU on colon cancer cells, accompanied by a reduction of in vitro 5-FU cytotoxicity in aggressive SW-620 cancer cells.
- Renck, Daiana,MacHado, Pablo,Souto, Andre A.,Rosado, Leonardo A.,Erig, Thais,Campos, Maria M.,Farias, Caroline B.,Roesler, Rafael,Timmers, Luis F. S. M.,De Souza, Osmar N.,Santos, Diogenes S.,Basso, Luiz A.
-
supporting information
p. 8892 - 8902
(2013/12/04)
-
- Solvent and structural effects on the UV-Vis absorption spectra of some 4,6-disubstituted-3-cyano-2-pyridones
-
A series of 4,6-disubstituted-3-cyano-2-pyridones was synthesized and their UV-Vis absorption spectra were recorded in the region 200-600 nm in the set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen-bonding interactions on the spectral shifts were analyzed by means of the linear solvation energy relationship concept of Kamlet and Taft. The influence of solvents as well as substituents on the 2-pyridone/2-hydroxypyridine tautomeric equilibration was evaluated. The absorption band maximum of the 2-hydroxypyridine form is found to appear at a shorter wavelength than that of the 2-pyridone form in all investigated solvents. The replacement of the methyl and phenyl groups at position 6 of the pyridone ring, by a hydroxy group, significantly changes the solvatochromic behavior of the investigated pyridones.
- Alimmari, Adel S. A.,Bozic, Bojan Crossed D Sign.,Marinkovic, Aleksandar D.,Mijin, Dusan Z.,Uscumlic, Gordana S.
-
p. 1825 - 1835
(2013/04/24)
-
- Azaindenoisoquinolines as topoisomerase i inhibitors and potential anticancer agents: A systematic study of structure-activity relationships
-
A comprehensive study of a series of azaindenoisoquinoline topoisomerase I (Top1) inhibitors is reported. The synthetic pathways have been developed to prepare 7-, 8-, 9-, and 10-azaindenoisoquinolines. The present study shows that 7-azaindenoisoquinolines possess the greatest Top1 inhibitory activity and cytotoxicity. Additionally, the introduction of a methoxy group into the D-ring of 7-azaindenoisoquinolines improved their biological activities, leading to new lead molecules for further development. A series of QM calculations were performed on the model "sandwich" complexes of azaindenoisoquinolines with flanking DNA base pairs from the Drug-Top1-DNA ternary complex. The results of these calculations demonstrate how changes in two forces contributing to the π-π stacking (dispersion and charge-transfer interactions) affect the binding of the drug to the Top1-DNA cleavage complex and thus modulate the drug's Top1 inhibitory activity.
- Kiselev, Evgeny,Agama, Keli,Pommier, Yves,Cushman, Mark
-
experimental part
p. 1682 - 1697
(2012/05/04)
-
- BICYCLIC INHIBITORS OF ANAPHASTIC LYMPHOMA KINASE
-
Disclosed are compounds of formula (Ⅰ) and their pharmaceutical acceptable salts, wherein R1, R2, R3, X, Y, Z, A, B, G1, m and n are defined in the description. The compositions containing the said compounds used for inhibiting kinases such as anaphastic lymphoma kinase (ALK) and methods of treating diseases such as cancer are disclosed.
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Page/Page column 136
(2012/08/07)
-
- BICYCLIC INHIBITORS OF ALK
-
The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, Formula (1) wherein R1, R2, R3, X, Y, Z, A, B, G1, m, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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Page/Page column 71
(2012/08/07)
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- KAl(SO4)2·12H2O catalyzed efficient synthesis of 3,4,6-trisubstituted 2-pyridone in water
-
An efficient green protocol for the preparation 3,4,6-trisubstituted 2-pyridone of employing a condensation reaction of cyanoacetamide and acetylacetone in the presence of KAl(SO4)2·12H 2O in water has been described. The present procedure offers advantage such as shorter reaction time, simple workup, and excellent yields.
- Heravi, Majid M.,Oskooie, Hossein A.,Karimi, Narges,Hamidi, Hoda
-
experimental part
p. 1059 - 1062
(2012/06/01)
-
- 1,4-Diaza-bicyclo[2,2,2]octane as a novel and efficient catalyst for the synthesis of 3,4,6-trisubstituted 2-pyridone derivatives
-
3,4,6-Trisubstituted 2-pyridone derivatives have been synthesized in good to excellent yields through a condensation reaction of various 1,3-diketones with amides in the presence of 1,4-Diaza-bicyclo[2,2,2]octane (DABCO) at reflux temperature.
- Heravi, Majid M.,Tahershamsi, Leili,Oskooie, Hossein A.,Baghernejad, Bita
-
experimental part
p. 670 - 672
(2010/10/19)
-
- Online monitoring of microwave-enhanced reactions by UV/Vis spectroscopy
-
Microwave-enhanced reactions are very fast in comparison to thermal reactions. They are often finished within a few minutes. Thus, the determination of the end point often fails, because conventional analytical methods are too slow. We developed a fast method using a UV/Vis sensor, which allows a direct online monitoring of the reaction process. The potency of the method is demonstrated by means of five representative reactions.
- Heller, Eberhard,Kloeckner, Jessica,Lautenschlaeger, Werner,Holzgrabe, Ulrike
-
experimental part
p. 3569 - 3573
(2010/08/22)
-
- SOLUBLE FORMS OF INCLUSION COMPLEXES OF HISTONE DEACETYLASE INHIBITORS AND CYCLODEXTRINS, THEIR PREPARATION PROCESSES AND USES IN THE PHARMACEUTICAL FIELD
-
The invention relates to the preparation of soluble forms of complexes of histone deacetylase inhibitors and cyclodextrins. The preparation process involves the formation of inclusion complexes with cyclodextrins with the aid of microwaves. Their use is in the pharmaceutical field.
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Page/Page column 22
(2008/12/07)
-
- WATER-SOLUBLE COMPLEX DYE, RECORDING FLUID, AND METHOD OF RECORDING
-
A water-soluble complex dye capable of forming an image having light resistance, ozone resistance and high saturation; a water-based recording fluid, particularly an ink jet recording fluid, employing such a dye; an ink set employing such a recording fluid; and an ink jet recording method, are presented.ψA water-soluble complex dye comprising an azo compound represented by the following formula (1) or its tautomer, and transition metal ions; a water-based recording fluid, particularly an ink jet recording fluid, containing such a dye; and an ink jet recording method employing such a recording fluid.ψIn the formula (1), A1 is a 5- to 7-membered hetero monocyclic group or a fused polycyclic group containing such a hetero monocyclic group and may have an optional substituent, but it represents a group which does not have a hydroxyl group at a position adjacent to the carbon bonded to the azo group; ring X1 represents a monocyclic hetero ring constituted by six atoms, bonded to the azo group and may have an optional substituent; and each of R1 and R2 which are independent of each other, is a hydrogen atom or a monovalent substituent.
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Page/Page column 63
(2008/06/13)
-
- Synthesis and Reactivity of 2,6-Diamino-4-methyl-3-pyridinecarbonitrile
-
2,6-Dihydroxy-4-methyl-3-pyridinecarbonitrile is converted via its 2,6-dichloro analog into the corresponding 2-amino-6-chloro, 2-chloro-6-amino, and 2,6-diamino derivatives.The last reacts with benzenesulfonyl chloride to yield a tris-sulfonyl derivative, the structure of which is demonstrated by X-ray analysis.
- Katritzky, Alan R.,Rachwal, Stanislaw,Smith, Terrance P.,Steel, Peter J.
-
p. 979 - 984
(2007/10/02)
-
- Pyridine and pyrimidine ring syntheses from 4-(4-morpholino)-3-pentenone and from ethyl 3-(4-morpholino)-2-butenoate
-
3-Substituted 2(1H)-pyridones are produced from reaction of 4-(4- morpholino)-3-pentenone 1 with each of the following carbon acids: cyanoacetamide, malononitrile, cyanothioacetamide, acetylacetamide, benzoyl- acetonitrile. Reaction of ethyl 3-(4-morpholino)-2-butenoate 2 with cyanoacetamide gives the corresponding hydroxypyridone. Pyrimidines are formed by reaction of 1 and of 2 with benzamidine and with S-benzylthiourea; in the last case, the eliminated morpholine displaces the benzylthio group to give the final product.
- Ratemi,Namdev,Gibson
-
p. 1513 - 1516
(2007/10/02)
-
- Synthesis of amphikuemin and analogs: a synomone that mediates partner-recognition between anemonefish and sea anemone
-
Amphikuemin (1), a compound that is responsible for partner-recognition at the first encounter between anemonefish and sea anemones, has been synthesized to confirm its structure and to supply material for further biological studies.Synthesis of amphikuemin analogs (11-15) is also described.
- Konno, Katsuhiro,Qin, Guo-wei,Nakanishi, Koji
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p. 247 - 251
(2007/10/02)
-
- 2-SUBSTITUTED 1,2-BENZISOTHIAZOL-3(2H)-ONE 1,1-DIOXIDE USEFUL AS AN ANXIOLYTIC AGENT
-
There is disclosed the compound 2-[4-[4-(2,7-naphthyridin-1-yl)-1-piperazinyl]butyl]-1,2-benzisothiazol-3(2 H)-one 1,1-dioxide, and the method of producing said compound, and the pharmaceutically acceptable salts thereof, and the use of said compound as an anxiolytic agent having a low liability for extrapyramidal side effects.
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-
- Synthesis of N-Acylacetoacetamide using 2,2,6-Trimethyl-1,3-dioxin-4-one
-
Diketene-acetone adduct (2,2,6-trimethyl-1,3-dioxin-4-one) 1 reacts with amide NH to give the corresponding N-acetoacetates 2.Formamide and basic amides such as picolinamide, on treatment with the adduct, are transformed to the N-acyl-2,6-dimethyl-4-oxo-4H-pyran-3-carboxamide (4a and 4p) together with the corresponding N-acetoacetates.Keywords--diketene-acetone adduct; 1,3-dioxin-4-one; acetylketene; diketene; acetoacetylation; 4-pyrone derivatives; N-acylacetoacetamide
- Sato, Masayuki,Kanuma, Norio,Kato, Tetsuzo
-
p. 1315 - 1321
(2007/10/02)
-
- Arylazoarylazo-substituted azo, azomethine 1:2 chromium complex dyes
-
1:2 Chromium complex dyes of the formula STR1 wherein A is the radical of a diazo component of the benzene or naphthalene class which carries the complex forming group X in ortho-position to the azo group, B is the radical of a coupling component which couples in ortho-position to the oxy group, D is the radical of an amine of the benzene or naphthalene class which carries the complex-forming group in ortho-position to the azo group, X is an oxygen atom or a --CO--O-- group, Ar is an aromatic carbocyclic radical. Ar' and A" are aromatic carbocyclic or heterocyclic radicals, q is an integer from 0 to 5, n is an integer from 1 to 3, m is an integer from 0 to 2 and p is 0 or 1, but the sum of n+m may be at most 3, and wherein the benzene ring can carry a further fused benzene ring or can be substituted by halogen, nitro, alkyl or alkoxy, and K+ is a cation. The water-insoluble dyes are useful in dyeing polyamide textile material and for coloring leather, oil vanishes, and paper as well as viscose, polyamide, cellulose ether and cellulose ester spinning compositions, and the water-soluble dyes are useful in dyeing leather, wool, silk, casein, polyamide and polyurethane fibers and furs; and the dyes possess good covering power and fastness properties.
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-
- Process for the manufacture of 6-hydroxypyrid-2-ones
-
The manufacture of 6-hydroxypyrid-2-ones is achieved by reacting a cyanoacetamide with an acetoacetic acid ester at temperatures of 50° to 200° C. and a pressure of 0.5 to 50 bars in an aqueous solution or suspension in the presence of an amine in a molar amount at least equal to that of the cyanoacetamide reactant.
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-
-
- A Novel Method for the Synthesis of Pyridones
-
A novel method for the synthesis of pyridones has been developed.It consists of the reaction of β-dicarbonyl compounds or conjugated enol ethers with cyanoacetamide in the presence of triethylbenzylammonium chloride in aq.NaOH solution.The present method is superior to the literature methods with respect to yield, ease of preparation and absence of organic solvent.
- Hawaldar, V. S.,Sunthankar, S. V.
-
p. 151 - 152
(2007/10/02)
-
- Water soluble cationic azo dyestuffs containing a cyclammonium group
-
A mixture of water soluble cationic azo dyestuffs devoid of carboxylic acid or sulphonic acid groups, each dyestuff in said mixture containing at least one cyclammonium group and said dyestuffs differing only in the constitution of the said cyclammonium group, said cyclammonium group being a gamma-picolinium group in one dyestuff and a beta-picolinium group in another dyestuff in said mixture, the water-solubility of said mixture being superior to that of the individual dyestuffs, the mixture being particularly useful for the coloration of polymers and copolymers of acrylonitrile.
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-
- Process for preparation of 5-cyanopyrid-6-ones
-
5-Cyanopyrid-6-ones are manufactured by reacting haloacetic acid esters with nitrogen compounds, then reacting the mixture with alkali metal cyanides, and finally reacting it with dicarbonyl compounds. The products are starting materials for the manufacture of dyes, assistants, pharmaceuticals, vitamin B 6, crop protection agents and aminoacids.
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-
- Chromium complex dye, including azo and azo methine dye compounds
-
1:2 Chromium complex dyes of an azo compound of the formula STR1 and an azomethine compound of the formula STR2 COMPLEXED TO A CHROMIUM ATOM, WHEREIN A is an ortho-phenylene or -- naphthylene diazo component radical; B is an ortho-phenylene or -- naphthylene coupling component radical; X is --O-- or --CO--O--; X' is --O--, --NH--, --N(lower alkyl)--, --N(aralkyl)-- or --N(aryl)--; R is an aliphatic radical; the benzene ring "a" is unsubstituted or substituted by a fused benzene ring, halo, nitro alkyl or alkoxy; the molecule containing 0-5 water solubilizing groups and optionally a group of the formula --N=N--Ar--N=N--Ar' and/or -N=N--Ar" wherein Ar, Ar' and Ar" represent an aromatic or carbocyclic radical.
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